Technical Blog
John GarnerJohn Garner, General Manager

A blog dedicated to answering technical questions in an open format relating to products from PolySciTech, a division of Akina, Inc.


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New Product Offerings: PolySciTech in 2023

Wednesday, February 1, 2023, 3:12 PM ET

AKiNAfil™ 3D Printer Filament (https://akinainc.com/polyscitech/products/akinafil/) Biodegradable PLGA with controlled molecular weight and LA:GA ratio custom extruded into 1.7 or 2.8 mm sized filaments for use in 3D printing applications.

RiPurpose™ Olig1000-700 (https://akinainc.com/polyscitech/products/ripurpose/) recycled polyethylene terephthalate oligomer/Prepolymer for use in synthesis of many types of plastics both for biodegradable as well as commodity/industrial applications.

PolySciTech Cationic Polymers (https://akinainc.com/polyscitech/products/polyvivo/#CationizablePolymers) PLGA copolymers with cationic endcaps for delivery of nucleic acids including DNA/RNA for use in a wide range of genetic applications including vaccine and immunotherapy development.

Video: https://youtu.be/keK1bOHIxV0

PLA from PolySciTech used in research on improved encapsulation of ionic hydrophilic drugs into nanoparticles by use of counterions

Thursday, January 26, 2023, 3:16 PM ET

Encapsulating drugs into nanoparticles requires that the drug be formulated in such a way that it prefers to be in the middle of the particle during emulsion formation. For hydrophobic drugs this is straightforward as these drugs have naturally poor solubility and prefer to be in the oil-soluble interior of polymeric particles. Hydrophilic drugs, however, are significantly more difficult as they tend to leave the nanoparticles during formation leading to poor drug loading. This phenomenon can be reduced by balancing the charges on a hydrophilic drug with a suitable counter charge on a relatively hydrophobic molecule, for example interacting a positively charged drug molecule with negatively charged palmitic acid. Recently, researchers From AstraZeneca and Purdue University used polylactide (cat# AP001) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a series of nanoparticles using a wide array of counter-charge ions and tested these particles for their ability to encapsulate and release AZD2811. This research holds promise to improve the use of nanoparticles to carry a wide range of hydrophilic compounds. Read more: Dimiou, Savvas, James McCabe, Rebecca Booth, Jonathan Booth, Kalyan Nidadavole, Olof Svensson, Anders Sparén et al. "Selecting Counterions to Improve Ionized Hydrophilic Drug Encapsulation in Polymeric Nanoparticles." Molecular Pharmaceutics (2023). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.2c00855

“Hydrophobic ion pairing (HIP) can successfully increase the drug loading and control the release kinetics of ionizable hydrophilic drugs, addressing challenges that prevent these molecules from reaching the clinic. Nevertheless, polymeric nanoparticle (PNP) formulation development requires trial-and-error experimentation to meet the target product profile, which is laborious and costly. Herein, we design a preformulation framework (solid state screening, computational approach, and solubility in PNP-forming emulsion) to understand counterion−drug−polymer interactions and accelerate the PNP formulation development for HIP systems. The HIP interactions between a small hydrophilic molecule, AZD2811, and counterions with different molecular structures were investigated. Cyclic counterions formed amorphous ion pairs with AZD2811; the 0.7 pamoic acid/1.0 AZD2811 complex had the highest glass transition temperature (Tg; 162 °C) and the greatest drug loading (22%) and remained as phase-separated amorphous nanosized domains inside the polymer matrix. Palmitic acid (linear counterion) showed negligible interactions with AZD2811 (crystalline-free drug/counterion forms), leading to a significantly lower drug loading despite having similar log P and pKa with pamoic acid. Computational calculations illustrated that cyclic counterions interact more strongly with AZD2811 than linear counterions through dispersive interactions (offset π−π interactions). Solubility data indicated that the pamoic acid/AZD2811 complex has a lower organic phase solubility than AZD2811- free base; hence, it may be expected to precipitate more rapidly in the nanodroplets, thus increasing drug loading. Our work provides a generalizable preformulation framework, complementing traditional performance-indicating parameters, to identify optimal counterions rapidly and accelerate the development of hydrophilic drug PNP formulations while achieving high drug loading without laborious trial-and-error experimentation. KEYWORDS: in situ hydrophobic ion pairing, counterion−drug−polymer interactions, solid-state characterization, computational modeling, solubility measurements, polymeric nanoparticle formulation”

Video Link: https://youtu.be/PwF5tZ_GlLk

Block copolymers (PEG-PLGA, PEG-PLA, PEG-PCL) from PolySciTech used in systematic investigation on conditions of nanoparticle formation

Tuesday, January 17, 2023, 2:34 PM ET

Due to their dual-nature of hydrophilicity and hydrophobicity, block copolymers have the capacity to spontaneously form nanoparticles under the correct conditions. The mechanism by which nanoparticles form is driven by a complex mixture of interfacial interactions and physics. The various conditions under which the particles form have a significant impact on the particles formulation and behavior. Recently, researchers at The University of Adelaide, The University of Queensland (Australia), Zhejiang University (China) and Harvard University (USA) used PEG-PLGA (cat# AK010 and AK026), PEG-PLA (cat# AK168), and mPEG-PCL (cat# AK128) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create nanoparticles under controlled conditions and evaluated these in response to loading of model drugs and particle behavior. This research holds promise to improve the controlled formation of nanoparticles in the future. Read more: Yang, Guangze, Yun Liu, Song Jin, Yue Hui, Xing Wang, Letao Xu, Dong Chen, David Weitz, and Chun‐Xia Zhao. "Phase separation‐induced nanoprecipitation for making polymer nanoparticles with high drug loading." Aggregate: e314. https://onlinelibrary.wiley.com/doi/abs/10.1002/agt2.314

“Increasing drug loading remains a critical challenge in the development and translation of nanomedicine. High drug-loading nanoparticles have demonstrated unique advantages such as less carrier material used, better-controlled drug release, and improved efficacy and safety. Herein, we report a simple and efficient salt concentration screening method for making polymer nanoparticles with exceptionally high drug loading (up to 66.5 wt%) based on phase separation-induced nanoprecipitation. Upon addition of salt, phase separation occurs in a miscible solvent-water solution delaying the precipitation time of drugs and polymers to different extents, facilitating their co-precipitation thus the formation of high drug-loading nanoparticles with high encapsulation efficiency (>90%) and excellent stability (>1 month). This technology is versatile and easy to be adapted to various hydrophobic drugs, different polymers, and solvents. This salt-induced nanoprecipitation strategy offers a novel approach to fabricating polymer nanoparticles with tunable drug loading, and opens great potentials for future nanomedicines. KEYWORDS drug loading, liquid-liquid phase separation, nanoparticles, nanoprecipitation, salt”

Video link: https://youtu.be/XTgAtYMVEq4

Chemical recycling of poly(ethylene terephthalate) into heterotelechelic PET oligomers provides new product available from Akina, Inc.

Monday, January 9, 2023, 4:23 PM ET

In partnership with RiKarbon, PolySciTech division of Akina, Inc. is offering PET oligomeric precursor (RiPurposeTM, Patent pending # 63/312519) (https://akinainc.com/polyscitech/products/ripurpose/index.php) This versatile precursor can be utilized in a wide array of reactions. Unlike carboxytelechelic (which only has terminal carboxylic acid groups) or hydroxytelechelic (only has terminal alcohol groups) RiPurpose contains both functional end-groups allowing for direct reactions with a variety of comonomers to directly form plastic groups. Find out more and obtain a sample to test out your ideas with at PolySciTech.

Fluorescently labelled PEG-PLGA from PolySciTech used in research on effect of nanoparticle shape towards behavior

Friday, January 6, 2023, 9:25 AM ET

Much still remains to be learned about how nanoparticles interact with cells and living systems. Due to the small size of nanoparticles (typically ~0.1 – 1 µm, < 1% the size of a typical human cell at 100 µm) they have the ability to transfer into cells or interact with surface proteins to elicit desired responses. Researchers at Hacettepe University and Süleyman Demirel University (Turkey) used fluorescently labelled mPEG-PLGA-FKR560 (AV021) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create labelled nanoparticles with controlled shape profiles. They investigated the effects of shape on drug release, cell interactions, and biodistribution. This research holds promise to improve the utilization of nanoparticles for disease treatment. Read more: Kaplan, Meryem, Kıvılcım Öztürk, Süleyman Can Öztürk, Ece Tavukçuoğlu, Güneş Esendağlı, and Sema Calis. "Effects of Particle Geometry for PLGA-Based Nanoparticles: Preparation and In Vitro/In Vivo Evaluation." Pharmaceutics 15, no. 1 (2023): 175. https://www.mdpi.com/article/10.3390/pharmaceutics15010175

“Abstract: The physicochemical properties (size, shape, zeta potential, porosity, elasticity, etc.) of nanocarriers influence their biological behavior directly, which may result in alterations of the therapeutic outcome. Understanding the effect of shape on the cellular interaction and biodistribution of intravenously injected particles could have fundamental importance for the rational design of drug delivery systems. In the present study, spherical, rod and elliptical disk-shaped PLGA nanoparticles were developed for examining systematically their behavior in vitro and in vivo. An important finding is that the release of the encapsulated human serum albumin (HSA) was significantly higher in spherical particles compared to rod and elliptical disks, indicating that the shape can make a difference. Safety studies showed that the toxicity of PLGA nanoparticles is not shape dependent in the studied concentration range. This study has pioneering findings on comparing spherical, rod and elliptical disk-shaped PLGA nanoparticles in terms of particle size, particle size distribution, colloidal stability, morphology, drug encapsulation, drug release, safety of nanoparticles, cellular uptake and biodistribution. Nude mice bearing non-small cell lung cancer were treated with 3 differently shaped nanoparticles, and the accumulation of nanoparticles in tumor tissue and other organs was not statistically different (p > 0.05). It was found that PLGA nanoparticles with 1.00, 4.0 ± 0.5, 7.5 ± 0.5 aspect ratios did not differ on total tumor accumulation in non-small cell lung cancer. Keywords: nanoparticles; particle shape; anisotrop; human serum albumin; cellular uptake; biodistribution; drug delivery; PLGA”

Video: https://youtu.be/XvyUtcuQO-g

PLLA from PolySciTech used in development of PLA-Chitosan electrospun mesh for tissue engineering

Thursday, January 5, 2023, 4:32 PM ET

As a means to prevent stroke, Carotid Endarterectomy is commonly performed to improve the vessel condition for transporting blood to the brain. However, there is significant risk with this procedure of the vessel reclosing or other complications. A better option is to utilize a scaffold which will allow for the growth of a wider vessel to repair or replace the damaged one. Recently, researchers at Universitas Airlangga (Indonesia) used PLLA (Cat# AP006) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create a composite mesh for vessel repair. This research holds promise to improve treatment of vascular diseases. Read More: Salsabila, Dhea Saphira, Prihartini Widiyanti, Edric Hernando, Indira Maretta Hulu, and Tarissa Diandra Putri Wibowo. "Characterization of Coaxially Electrospun Poly (L-Lactic) Acid/Chitosan with Heparin Modification as Patch Angioplasty Candidate." Journal of Membrane Science and Research 9, no. 1 (2023). http://www.msrjournal.com/&url=http:/www.msrjournal.com/article_699986.html

“Atherosclerosis in the carotid artery is the leading cause of ischemic stroke. Carotid Endarterectomy (CEA) is a procedure of atherosclerosis plaque removal to prevent stenosis, which significantly reduces the risk of transient ischemic attack. Currently, the application of commercialized patch grafts in CEA has shown several disadvantages regarding its incompatibility with the carotid artery. Poly (L-Lactic) Acid (PLLA)/Chitosan (CS) electrospun fibers with heparin modification were fabricated as biocompatible patch graft through coaxial electrospinning with composition variations of 1:0; 1:2; 1:3; 1:4. Pre-synthesis measurement of viscosity and surface tension was conducted to optimize the electrospinnability of PLLA 10% and CS 3% (w/v). FTIR results confirmed the existence of each material's functional group. Physical and mechanical properties were enhanced along with the increased PLLA/CS ratio. The hydrophilicity was optimized by the 1:4 electrospun fibers, which reduced the contact angle to 27°. The 1:4 electrospun fibers also resulted in a suitable degradation rate within 72 days and desirable tensile strength at 3.864 with 24.8% elongation. According to the results, Poly (L-Lactic) Acid/Chitosan electrospun fibers have a promising potential as a patch angioplasty candidate”

Video: https://youtu.be/i9SY5aS8x10

Fluorescent PLGA-Rhodamine from PolySciTech used in the development of inhalable, antimicrobial nanoparticles

Thursday, January 5, 2023, 4:32 PM ET

Antimicrobial resistance creates a significant barrier to treatment of bacterial infection. SET-M33, a non-natural antimicrobial peptide, can be used for treatment of cystic fibrosis however requires a delivery mechanism to provide it to the appropriate location in the lung tissue. Recently researchers at University of Siena, SetLance srl, University of Campania, and University of Naples used PLGA-Rhodamine (Cat # AV011) from PolySciTech division of Akina, Inc. (www.polyscitech.com) in development of an SET-M33 delivery nanoparticle. This research holds promise to improve treatment of lung-bacterial infections. Read more: Cresti, Laura, Gemma Conte, Giovanni Cappello, Jlenia Brunetti, Chiara Falciani, Luisa Bracci, Fabiana Quaglia, Francesca Ungaro, Ivana d’Angelo, and Alessandro Pini. "Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo." Pharmaceutics 15, no. 1 (2023): 3. https://www.mdpi.com/2017528

“Abstract: Development of inhalable formulations for delivering peptides to the conductive airways and shielding their interactions with airway barriers, thus enhancing peptide/bacteria interactions, is an important part of peptide-based drug development for lung applications. Here, we report the construction of a biocompatible nanosystem where the antimicrobial peptide SET-M33 is encapsulated within polymeric nanoparticles of poly(lactide-co-glycolide) (PLGA) conjugated with polyethylene glycol (PEG). This system was conceived for better delivery of the peptide to the lungs by aerosol. The encapsulated peptide showed prolonged antibacterial activity, due to its controlled release, and much lower toxicity than the free molecule. The peptide-based nanosystem killed Pseudomonas aeruginosa in planktonic and sessile forms in a dose-dependent manner, remaining active up to 72 h after application. The encapsulated peptide showed no cytotoxicity when incubated with human bronchial epithelial cells from healthy individuals and from cystic fibrosis patients, unlike the free peptide, which showed an EC50 of about 22 µM. In vivo acute toxicity studies in experimental animals showed that the peptide nanosystem did not cause any appreciable side effects, and confirmed its ability to mitigate the toxic and lethal effects of free SET-M33. Keywords: polymeric nanoparticles; lung delivery; inhalable formulations; nanoparticle properties; aerosolization; nanoparticle/mucus interactions; antimicrobial peptides; antimicrobial resistance; Pseudomonas aeruginosa”

Video: https://youtu.be/looWDKpAwFY

Fluorescent PLGA-CY5 from PolySciTech used in development of layer-by-layer nanoparticles as analytical tools for understanding the blood-brain-barrier

Tuesday, December 20, 2022, 4:51 PM ET

Unlike most organs in the human body, the brain has a significant barrier against uptake of medicinal compounds present in the blood. Crossing this barrier is difficult for anything other than small, hydrophobic molecules and is particularly challenging for nanoparticles. This barrier is poorly understood and the exact features and properties of a particle which allow it to either pass or, not pass, through the barrier has not been fully characterized. Researchers at Massachusetts Institute of Technology used PLGA-CY5 (cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fluorescently trackable nanoparticles. They tested these particles with a variety of configurations and surface chemistries against model brain barrier systems to further understand what properties control this transport. This research holds promise to improve delivery of therapeutics to the brain in the future. Read more: Lamson, Nicholas G., Andrew J. Pickering, Jeffrey Wyckoff, Priya Ganesh, Joelle P. Straehla, and Paula T. Hammond. "Core material and surface chemistry of Layer-by-Layer (LbL) nanoparticles independently direct uptake, transport, and trafficking in preclinical blood-brain barrier (BBB) models." bioRxiv (2022). https://www.biorxiv.org/content/10.1101/2022.10.31.514595.abstract

“Development of new treatments for neurological disorders, especially brain tumors and neurodegenerative diseases, is hampered by poor accumulation of new therapeutic candidates in the brain. Drug carrying nanoparticles are a promising strategy to deliver therapeutics, but there is a major need to understand interactions between nanomaterials and the cells of the blood-brain barrier (BBB), and to what degree these interactions can be predicted by preclinical models. Here, we use a library of eighteen layer-by-layer electrostatically assembled nanoparticles (LbL-NPs) to independently assess the impact of nanoparticle core stiffness and surface chemistry on in vitro uptake and transport in three common assays, as well as intracellular trafficking in hCMEC/D3 endothelial cells. We demonstrate that nanoparticle core stiffness impacts the magnitude of material transported, while surface chemistry influences how the nanoparticles are trafficked within the cell. Finally, we demonstrate that these factors similarly dictate in vivo BBB transport using intravital imaging through cranial windows in mice, and we discover that a hyaluronic acid surface chemistry provides an unpredicted boost to transport. Taken together, these findings highlight the importance of considering factors such as assay geometry, nanomaterial labelling strategies, and fluid flow in designing preclinical assays to improve nanoparticle screening throughput for drug delivery to the brain.”

See Video: https://youtu.be/fAHFUmqonmc

mPEG-PLA from PolySciTech used in development of ultrasound triggered nanocarrier particles

Tuesday, December 20, 2022, 4:50 PM ET

Targeted drug delivery in a living body can be achieved by applying a non-invasive ‘trigger’ which creates a change in the delivery carrier that releases the medicinal compound from the system. This can be done by using low intensity ultrasound which can cause nanoparticles to release their payload of medicine at the location where the ultrasound is focused. Researchers at University of Utah used mPEG-PLA (Cat# AK009) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles that can be triggered by ultrasound to release on demand. This research holds promise to provide for controlled, localized drug delivery. Read more: Wilson, Matthew G., Aarav Parikh, and Jan Kubanek. "Effective ultrasound-triggered drug release from stable nanocarriers." bioRxiv (2022): 2021-12. https://www.biorxiv.org/content/10.1101/2021.12.14.471689.abstract

“Abstract: Selective delivery of concentrated medication into specified targets would realize the promise of effective personalized medicine with minimal side effects. Low-intensity ultrasound provides noninvasive and practical means to deliver drugs from nanocarriers selectively into its focus. However, which nanocarriers and ultrasound parameters can provide effective and safe drug delivery has been unclear. We found that nanocarriers with highly stable perfluorocarbon cores mediate effective release so long as they are activated by ultrasound of relatively low frequencies. We further demonstrated a repeatable method for manufacturing these nanocarriers to help facilitate future work in this area. This study guides the formulation and release parameters for effective and safe drug delivery into specific parts of the body or brain regions.”

See Video: https://youtu.be/8G2X1pIc2sg

PLGA-PEG and PLGA-PEG-Mal from PolySciTech used in development of antimicrobial peptide decorated nanoparticles.

Tuesday, December 20, 2022, 4:49 PM ET

Bacterial infection often prevents and delays healing in wounds. Antimicrobial peptides can provide for treatment of infections, however these are quickly degraded and become inactive in vivo. One strategy to provide for the delivery of these peptides is to conjugate them onto the surface of nanoparticles. Researchers at Universidade do Porto and Universidade Católica do Porto (Portugal) used PLGA-PEG-Mal (Cat# AI110) and mPEG-PLGA (Cat# AK102) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles functionalized with antimicrobial peptides for treatment of bacterial infections. This research holds promise to improve therapies against wound infections. Read more: Ramôa, António Miguel, Filipa Campos, Luís Moreira, Cátia Teixeira, Victoria Leiro, Paula Gomes, José das Neves, M. Cristina L. Martins, and Cláudia Monteiro. "Antimicrobial peptide-grafted PLGA-PEG nanoparticles to fight bacterial wound infections." Biomaterials Science (2023). https://pubs.rsc.org/en/content/articlehtml/2023/bm/d2bm01127a

“Abstract: Wound infection treatment with antimicrobial peptides (AMPs) is still not a reality, due to the loss of activity in vivo. Unlike the conventional strategy of encapsulating AMPs on nanoparticles (NPs) leaving activity dependent on the release profile, this work explores AMP grafting to poly(D,L-lactide-co-glycolide)-polyethylene glycol NPs (PLGA-PEG NPs), whereby AMP exposition, infection targeting and immediate action are promoted. NPs are functionalized with MSI-78(4–20), an equipotent and more selective derivative of MSI-78, grafted through a thiol-maleimide (Mal) Michael addition. NPs with different ratios of PLGA-PEG/PLGA-PEG-Mal are produced and characterized, with 40%PLGA-PEG-Mal presenting the best colloidal properties and higher amounts of AMP grafted as shown by surface charge (+8.6 ± 1.8 mV) and AMP quantification (326 μg mL−1, corresponding to 16.3 μg of AMP per mg of polymer). NPs maintain the activity of the free AMP with a minimal inhibitory concentration (MIC) of 8–16 μg mL−1 against Pseudomonas aeruginosa, and 16–32 μg mL−1 against Staphylococcus aureus. Moreover, AMP grafting accelerates killing kinetics, from 1–2 h to 15 min for P. aeruginosa and from 6–8 h to 0.5–1 h for S. aureus. NP activity in a simulated wound fluid is maintained for S. aureus and decreases slightly for P. aeruginosa. Furthermore, NPs do not demonstrate signs of cytotoxicity at MIC concentrations. Overall, this promising formulation helps unleash the full potential of AMPs for the management of wound infections.”

See Video: https://youtu.be/_x6MYzpzmVU

PLA from PolySciTech used in testing of enzymatic degradation and potential application towards environmental cleanup of plastics

Tuesday, December 20, 2022, 4:48 PM ET

In addition to biomedical applications, polyesters are also applied for environmental considerations as the ester bonds in their backbone can be cleaved by water. In this case, polylactide and other polyesters can be used to further understand various degradation mechanisms which happen environmentally. Researchers from Consejo Superior de Investigaciones Científicas, Barcelona Supercomputing Center, Universidad de Oviedo, Bangor University, and Institució Catalana de Recerca i Estudis Avançats used PLA (Cat# AP224) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to study breakdown of esters under acidic conditions. Read more: Vidal, Paula, Mónica Martínez-Martínez, Laura Fernandez-Lopez, Sergi Roda, Celia Méndez-García, Olga V. Golyshina, Víctor Guallar, Ana I. Peláez, and Manuel Ferrer. "Metagenomic mining for esterases in the microbial community of Los Rueldos acid mine drainage formation." Frontiers in Microbiology 13 (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9162777/

“Acid mine drainage (AMD) systems are extremely acidic and are metal-rich formations inhabited by relatively low-complexity communities of acidophiles whose enzymes remain mostly uncharacterized. Indeed, enzymes from only a few AMD sites have been studied. The low number of available cultured representatives and genome sequences of acidophiles inhabiting AMDs makes it difficult to assess the potential of these environments for enzyme bioprospecting. In this study, using naïve and in silico metagenomic approaches, we retrieved 16 esterases from the α/β-hydrolase fold superfamily with the closest match from uncultured acidophilic Acidobacteria, Actinobacteria (Acidithrix, Acidimicrobium, and Ferrimicrobium), Acidiphilium, and other Proteobacteria inhabiting the Los Rueldos site, which is a unique AMD formation in northwestern Spain with a pH of ∼2. Within this set, only two polypeptides showed high homology (99.4%), while for the rest, the pairwise identities ranged between 4 and 44.9%, suggesting that the diversity of active polypeptides was dominated not by a particular type of protein or highly similar clusters of proteins, but by diverse non-redundant sequences. The enzymes exhibited amino acid sequence identities ranging from 39 to 99% relative to homologous proteins in public databases, including those from other AMDs, thus indicating the potential novelty of proteins associated with a specialized acidophilic community. Ten of the 16 hydrolases were successfully expressed in Escherichia coli. The pH for optimal activity ranged from 7.0 to 9.0, with the enzymes retaining 33–68% of their activities at pH 5.5, which was consistent with the relative frequencies of acid residues (from 54 to 67%). The enzymes were the most active at 30–65°C, retaining 20–61% of their activity under the thermal conditions characterizing Los Rueldos (13.8 ± 0.6°C). The analysis of the substrate specificity revealed the capacity of six hydrolases to efficiently degrade (up to 1,652 ± 75 U/g at pH 8.0 and 30°C) acrylic- and terephthalic-like [including bis(2-hydroxyethyl)-terephthalate, BHET] esters, and these enzymes could potentially be of use for developing plastic degradation strategies yet to be explored. Our assessment uncovers the novelty and potential biotechnological interest of enzymes present in the microbial populations that inhibit the Los Rueldos AMD system. Keywords: acidophiles, acidophilic bacteria, acid mine drainage, biodiversity, extremozymes, esterase, metagenomics, plastic”

Fluorescent PLGA-FKR648 from PolySciTech used in development of anticancer nanotherapeutics

Monday, December 19, 2022, 2:05 PM ET

Among brain cancers, glioblastoma is the most common and deadly primary malignant tumor in adults. In order to evaluate the efficacy of cancer therapeutics, it is important to replicate the tumor microenvironment so that the behavior of the medicine or delivery system matches that which is to be expected in-vivo. Researchers at Universidade do Porto (Portugal) used PLGA-FKR648 (Cat# AV015) from PolySciTech Division of Akina, Inc. (www.polyscitech.comto formulate traceable nanoparticles which can be observed by fluorescence techniques. They tested these nanoparticles against a novel model-cancer system consisting of carefully constructed artificial tumor microtissues grown in-vitro. This research holds promise to improve therapies against brain cancer. Read more: Martins, Cláudia, Catarina Pacheco, Catarina Moreira-Barbosa, Ângela Marques-Magalhães, Sofia Dias, Marco Araújo, Maria J. Oliveira, and Bruno Sarmento. "Glioblastoma immuno-endothelial multicellular microtissue as a 3D in vitro evaluation tool of anti-cancer nano-therapeutics." Journal of Controlled Release 353 (2023): 77-95. https://www.sciencedirect.com/science/article/pii/S0168365922007684

“Highlights: Glioblastoma heterotypic multicellular tumor microtissues (MCTMs) are generated. MCTMs mimic tumor organization, extracellular matrix production and necrosis. MCTMs respond to a tumor-targeted docetaxel (DTX) nanotherapy. MCTMs macrophages polarize into a M1-/M2-phenotype according to the nanotherapy. MCTMs exhibit a particular biomolecular cytokine signature after treatment. Abstract: Despite being the most prevalent and lethal type of adult brain cancer, glioblastoma (GBM) remains intractable. Promising anti-GBM nanoparticle (NP) systems have been developed to improve the anti-cancer performance of difficult-to-deliver therapeutics, with particular emphasis on tumor targeting strategies. However, current disease modeling toolboxes lack close-to-native in vitro models that emulate GBM microenvironment and bioarchitecture, thus partially hindering translation due to poorly predicted clinical responses. Herein, human GBM heterotypic multicellular tumor microtissues (MCTMs) are generated through high-throughput 3D modeling of U-251 MG tumor cells, tissue differentiated macrophages isolated from peripheral monocytes, and brain microvascular primary endothelial cells. GBM MCTMs mimicked tumor spatial organization, extracellular matrix production and necrosis areas. The bioactivity of a model drug, docetaxel (DTX), and of tumor-targeted DTX-loaded polymeric NPs with a surface L-Histidine moiety (H-NPs), were assessed in the MCTMs. MCTMs cell uptake and anti-proliferative effect was 8- and 3-times higher for H-NPs, respectively, compared to the non-targeted NPs and to free DTX. H-NPs provided a decrease of MCTMs anti-inflammatory M2-macrophages, while increasing their pro-inflammatory M1 counterparts. Moreover, H-NPs showed a particular biomolecular signature through reduced secretion of an array of medium cytokines (IFN-γ, IL-1β, IL-1Ra, IL-6, IL-8, TGF-β). Overall, MCTMs provide an in vitro biomimetic model to recapitulate key cellular and structural features of GBM and improve in vivo drug response predictability, fostering future clinical translation of anti-GBM nano-therapeutic strategies.”

PEG-PLGA from PolySciTech used in investigation of macrophage behavior in response to fiber elasticity

Wednesday, December 14, 2022, 4:46 PM ET

Human cells commonly respond to a wide array of environmental factors including oxygen, pH, external signals, hormones, and other properties of the area that they are in. When interacting with a surface or other component the cells will also react to the mechanical properties of the material they are adjacent to. Researchers at BenHealth Biopharmaceutical, DGENE Bighealth, and Chinese Academy of Science used a series of PEG-PLGA polymers (AK037, AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanofibers and allowed these to interact with macrophages. They found that the macrophages exhibit inflammatory activation in response to varying elastic modulus of the fibers. This research holds promise to provide for control of the human immune system. Read more: Zhang, Bokai, Massimiliano Galluzzi, Guoqiao Zhou, and Haoyang Yu. "A study of macrophage mechanical properties and functional modulation based on the Young's modulus of PLGA-PEG fibers." Biomaterials Science (2023). https://pubs.rsc.org/en/content/articlehtml/2023/bm/d2bm01351g

“Abstract: The immune response of macrophages plays an important role in defending against viral infection, tumor deterioration and repairing of contused tissue. Macrophage functional differentiation induced by nanodrugs is the leading edge of current research, but nanodrugs have toxic side effects, and the influence of their physical properties on macrophages is not clear. Here we create an alternative way to modulate macrophage function through PLGA-PEG fibers’ Young's modulus. Previously, we revealed that by controlling the Young's modulus of the fibers from kPa to MPa, all the fibers entered murine macrophage cells (RWA 264.7) in a similar manner, and based on that, we found that macrophages’ mechanical properties were affected by the fibers’ Young's modulus, that is, hard fibers with a Young's modulus of ∼1 MPa increased the cell average Young's modulus, but did not affect the cell shape, while soft fibers with a Young's modulus of ∼100 kPa decreased the cell average Young's modulus and modulated the cell shape to a more spherical one. On the other hand, only the soft fibers induced proinflammatory cytokine secretion, indicating an M1 macrophage functional modulation by low Young's modulus fibers. This study explored the mechanical properties of the interactions between PLGA-PEG fibers and cells, in particular, when guiding the direction of the modulation of macrophage function, which is of great significance for the applications of material biology in the biomedical field.”

PCL-PEG-COOH from PolySciTech used in preparation of sorafenib nanoparticles for cancer therapy

Wednesday, December 14, 2022, 4:44 PM ET

Amphiphilic block copolymers which have hydrophilic and hydrophobic chains have the ability to self-assemble into colloidal particles enabling delivery of drugs which have poor bioavailability. Sorafenib is a kinase inhibitor approved for the treatment of liver, kidney and thyroid cancers, however its poor solubility and side effects have limited its clinical applications. Researchers at University of Helsinki, University of Lisbon, Aalto University, and University of Groningen used PCL-PEG-COOH (Cat# AI157) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles with controlled interactions, size, and zeta-potential for delivery of sorafenib by leveraging microfluidic systems. This research holds promise to improve the utilization of microfluidics for cancer treatment. Read more: Känkänen, Voitto, Micaela Fernandes, Zehua Liu, Jani Seitsonen, Sami-Pekka Hirvonen, Janne Ruokolainen, João F. Pinto, Jouni Hirvonen, Vimalkumar Balasubramanian, and Hélder A. Santos. "Microfluidic preparation and optimization of sorafenib-loaded poly (ethylene glycol-block-caprolactone) nanoparticles for cancer therapy applications." Journal of Colloid and Interface Science (2022). https://www.sciencedirect.com/science/article/pii/S0021979722020987

“Abstract: The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality. Keywords: Block copolymers, Cancer, Microfluidics, Nanoparticles, Nanoprecipitation, Self-assembly”

PLGA from PolySciTech used in development of cell penetrating peptide decorated nanoparticles for pulmonary delivery to treat lung infection.

Tuesday, December 13, 2022, 4:06 PM ET

Utilizing systemic delivery methods to treat lung infections is associated with side effects due to poor delivery across cell barriers. Cell penetrating peptides (CPP) have a unique ability to cross cell membranes allowing for intracellular drug delivery. Researchers at University of Texas at Arlington and Southwestern Medical Center utilized PLGA (Cat# AP040) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles and combined these with CPP to provide for inhalable nanoparticles which can enter lung epithelial cells and treat bacterial or viral diseases. This research holds promise to improve therapies against several lung diseases. Read more: Chintapula, Uday, Su Yang, Trinh Nguyen, Yang Li, Justyn Jaworski, He Dong, and Kytai T. Nguyen. "Supramolecular Peptide Nanofiber/PLGA Nanocomposites for Enhancing Pulmonary Drug Delivery." ACS Applied Materials & Interfaces (2022). https://pubs.acs.org/doi/abs/10.1021/acsami.2c15204

“Abstract: Effective drug delivery to pulmonary sites will benefit from the design and synthesis of novel drug delivery systems that can overcome various tissue and cellular barriers. Cell penetrating peptides (CPPs) have shown promise for intracellular delivery of various imaging probes and therapeutics. Although CPPs improve delivery efficacy to a certain extent, they still lack the scope of engineering to improve the payload capacity and protect the payload from the physiological environment in drug delivery applications. Inspired by recent advances of CPPs and CPP-functionalized nanoparticles, in this work, we demonstrate a novel nanocomposite consisting of fiber-forming supramolecular CPPs that are coated onto polylactic-glycolic acid (PLGA) nanoparticles to enhance pulmonary drug delivery. These nanocomposites show a threefold higher intracellular delivery of nanoparticles in various cells including primary lung epithelial cells, macrophages, and a 10-fold increase in endothelial cells compared to naked PLGA nanoparticles or a twofold increase compared to nanoparticles modified with traditional monomeric CPPs. Cell uptake studies suggest that nanocomposites likely enter cells through mixed macropinocytosis and passive energy-independent mechanisms, which is followed by endosomal escape within 24 h. Nanocomposites also showed potent mucus permeation. More importantly, freeze-drying and nebulizing formulated nanocomposite powder did not affect their physiochemical and biological activity, which further highlights the translative potential for use as a stable drug carrier for pulmonary drug delivery. We expect nanocomposites based on peptide nanofibers, and PLGA nanoparticles can be custom designed to encapsulate and deliver a wide range of therapeutics including nucleic acids, proteins, and small-molecule drugs when employed in inhalable systems to treat various pulmonary diseases.”

PLGA from PolySciTech used in development of novel graphene cold-rolled material for microsensor development

Monday, December 12, 2022, 4:19 PM ET

The ability of PLGA to hydrolyze in the presence of water is commonly utilized in biomedical applications to deliver drugs in a long-acting formulation or for a cell scaffold. However, PLGA’s ability to degrade away can be utilized in manufacturing applications where a temporary structure which can be easily removed after it fulfills its purpose is desired. Researchers at University of Cincinnati and North Carolina A&T State University 3D printed a blend of PLGA (cat# AP234) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) with a nickel catalyst to create a temporary framework for synthesis of complex 3D graphite networks which could be manipulated into sensors for motion or mechanical stress. This research holds promise to provide for enhanced electronics and related components. Read more: Kondapalli, Vamsi Krishna Reddy, Guangqi Zhang, Yu Zhang, Mahnoosh Khosravifar, Kyle Brittingham, Nhat Phan, Sergey Yarmolenko, Je-Hyeong Bahk, and Vesselin Shanov. "Cold Rolling of 3d Graphene: Characterization and Applications." Available at SSRN 4294781. https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4294781

“Abstract: Previously, we reported 3D Shaped 3D Graphene (3D2G) with controlled structural pores. In this work, we introduce cold rolling as a post-processing technique to obtain compressed 3D2G referred to as C3D2G. The gravimetric density, electrical conductivity, and tensile strength of C3D2G were higher than 3D2G by 37.3, 53.4, and 24.9 times, respectively. The performed comprehensive materials characterization of C3D2G revealed the micro-motion of the graphene flakes from their random orientations into a stacked and aligned structure along with the extrusion of bulk material into the structural pores which acted as stress-relief spaces. Further, a new process was demonstrated enabling the welding of multiple pieces into one structure via cold rolling, thus showing potential for dimensional scaling up. The conducted tensile and electrical conductivity studies across the welded region revealed the presence of a mechanical bond within the joined area with a higher strength than the initial pieces involved in welding. Due to the enhanced properties of C3D2G, a unique application of this material was explored as a reusable, etch-resistant hard mask for patterning silicon wafers, and as a protective barrier against fluorine plasma environment. The etch rate measurements showed a higher etching resistance of C3D2G compared to Si and SiO2 when exposed to a fluorine plasma Reactive Ion Etching (RIE). Keywords: 3D graphene, CVD, additive manufacturing, cold rolling, dry etch, welding, hard masks, Reactive Ion Etching (RIE)”

PLGA from PolySciTech used in development of acidity control methodology for in-situ implants

Tuesday, December 6, 2022, 4:25 PM ET

As PLGA hydrolyzes, the products from this reaction are lactic and glycolic acid. Although these are relatively weak acids, they can contribute to the formation of a low pH (acidity formation) in the local environment which can both lead to inflammation as well as damage biological active pharmaceutics such as protein-based drugs. Researchers at Purdue University used PLGA (Cat# AP041) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to formulate in-situ forming implants and used these to investigate localized pH reduction due to PLGA degradation as well as develop methods to mitigate this effect using alkaline salts. This research holds promise to enable the use of PLGA for delivery of sensitive, protein-based drugs without damaging the APIs. Read more: Hopkins, Kelsey, Elizabeth Wakelin, Natalie Romick, Jacqueline Kennedy, Emma Simmons, and Luis Solorio. "Basic Salt Additives Modulate the Acidic Microenvironment Around In Situ Forming Implants." Annals of Biomedical Engineering (2022): 1-11. https://link.springer.com/article/10.1007/s10439-022-03109-6

“Abstract: There is a growing number of protein drugs, yet their limited oral bioavailability requires that patients receive frequent, high dose injections. In situ forming implants (ISFIs) for controlled release of biotherapeutics have the potential to greatly reduce the injection frequency and improve patient compliance. However, protein release from ISFIs is a challenge due to their proclivity for instability. Specifically, factors such as the acidic microclimate within ISFIs can lead to protein aggregation and denaturation. Basic salts have been shown in PLGA microparticle and microcylinder formulations to significantly reduce protein instability by neutralizing this acidic environment. The overall objective of the study was to demonstrate that basic salts can be used with an ISFI system to neutralize the implant acidification. To this end, the basic salts MgCO3 and Mg(OH)2 were added to a protein-releasing ISFI and the effect on drug release, pH, implant swelling, implant diffusivity, and implant erosion were evaluated. Either salt added at 3 wt% neutralized the acidic environment surrounding the implants, keeping the pH at 6.64 ± 0.03 (MgCO3) and 6.46 ± 0.11 (Mg(OH)2) after 28 day compared to 3.72 ± 0.05 with no salts added. The salts initially increased solution uptake into the implants but delayed implant degradation and erosion. The 3 wt% Mg(OH)2 formulation also showed slightly improved drug release with a lower burst and increased slope. We showed that salt additives can be an effective way to modulate the pH in the ISFI environment, which can improve protein stability and ultimately improve the capacity of ISFIs for delivering pH-sensitive biomolecules. Such a platform represents a low-cost method of improving overall patient compliance and reducing the overall healthcare burden.”

Fluorescent PLGA-CY5 from PolySciTech used in development of nanoparticle therapy for obesity treatment by controlling ‘the munchies’

Tuesday, December 6, 2022, 4:24 PM ET

Accumulation of fat in the liver can lead to significant morbidity including cirrhosis, fibrosis, as well as promotion of type 2 diabetes. Cannabinoid receptors in the liver recognize THC and related compounds which increases appetite (i.e. the so-called ‘munchies’ after smoking marijuana). However, these receptors also pick up endocannabinoids, which are similar chemical compounds naturally occurring in the human body. Blocking these receptors in the liver can reduce appetite and treat obesity, however interfering with these receptors in the brain where they are part of the endocannabinoid system can lead to deleterious side effects. Researchers at Obesity and Metabolism Laboratory, The Hebrew University of Jerusalem, and Hadassah Medical School used PLGA-CY5 (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a nanoparticle system to deliver cannabinoid blocker rimonabant in a targeted manner to the liver. This research holds promise to improve therapeutic options for obesity and related morbidity conditions such as diabetes and heart disease. Read more: Hirsch, S., Hinden, L., Naim, M.B.D., Baraghithy, S., Permyakova, A., Azar, S., Nasser, T., Portnoy, E., Agbaria, M., Nemirovski, A. and Golomb, G., 2023. Hepatic targeting of the centrally active cannabinoid 1 receptor (CB1R) blocker rimonabant via PLGA nanoparticles for treating fatty liver disease and diabetes. Journal of Controlled Release, 353, pp.254-269. https://www.sciencedirect.com/science/article/pii/S0168365922007866

“Highlights: Successful hepatic CB1 targeting with rimonabant was achieved using nanotechnology. Rimonabant-encapsulated in nanoparticles does not induce CNS-mediated side effects. Liver-targeted of rimonabant ameliorated hepatic steatosis and insulin resistance. Abstract: Over-activation of the endocannabinoid/CB1R system is a hallmark feature of obesity and its related comorbidities, most notably type 2 diabetes (T2D), and non-alcoholic fatty liver disease (NAFLD). Although the use of drugs that widely block the CB1R was found to be highly effective in treating all metabolic abnormalities associated with obesity, they are no longer considered a valid therapeutic option due to their adverse neuropsychiatric side effects. Here, we describe a novel nanotechnology-based drug delivery system for repurposing the abandoned first-in-class global CB1R antagonist, rimonabant, by encapsulating it in polymeric nanoparticles (NPs) for effective hepatic targeting of CB1Rs, enabling effective treatment of NAFLD and T2D. Rimonabant-encapsulated NPs (Rimo-NPs) were mainly distributed in the liver, spleen, and kidney, and only negligible marginal levels of rimonabant were found in the brain of mice treated by iv/ip administration. In contrast to freely administered rimonabant treatment, no CNS-mediated behavioral activities were detected in animals treated with Rimo-NPs. Chronic treatment of diet-induced obese mice with Rimo-NPs resulted in reduced hepatic steatosis and liver injury as well as enhanced insulin sensitivity, which were associated with enhanced cellular uptake of the formulation into hepatocytes. Collectively, we successfully developed a method of encapsulating the centrally acting CB1R blocker in NPs with desired physicochemical properties. This novel drug delivery system allows hepatic targeting of rimonabant to restore the metabolic advantages of blocking CB1R in peripheral tissues, especially in the liver, without the negative CB1R-mediated neuropsychiatric side effects.”

PCL-diacrylate from PolySciTech used in development of cationic-copolymer siRNA delivery system

Tuesday, December 6, 2022, 4:23 PM ET

Researchers at Ludwig-Maximillians University of Munich and University of Bern used PCL-diacrylate (custom) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to react with polyethylenimine to create a biodegradable cationic copolymer for nucleic delivery applications. This research holds promise to improve delivery of siRNA to cells which can be used to treat a wide range of disease states where selective silencing of genes can be beneficial. Read more: Jin, Yao, Friederike Adams, Judith Möller, Lorenz Isert, Christoph M. Zimmermann, David Keul, and Olivia M. Merkel. "Synthesis and Application of Low Molecular Weight PEI‐based Copolymers for siRNA Delivery with Smart Polymer Blends." Macromolecular bioscience (2022): 2200409. https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.202200409

“Abstract: Polyethylenimine (PEI) is a commonly used cationic polymer for small-interfering RNA (siRNA) delivery due to its high transfection efficiency at low commercial cost. However, high molecular weight PEI is cytotoxic and thus, its practical application is limited. In this study, we investigated different formulations of low molecular weight PEI (LMW-PEI) based copolymers PEI-PCL (800 Da-40 kDa) and PEI-PCL-PEI (5 kDa-5 kDa-5 kDa) blended with or without PEG-PCL (5 kDa-4 kDa) to prepare nanoparticles via nanoprecipitation using a solvent displacement method with sizes around 100 nm. PEG-PCL can stabilize the nanoparticles, improve their biocompatibility, and extend their circulation time in vivo. The nanoparticles composed of PEI-PCL-PEI and PEG-PCL showed higher siRNA encapsulation efficiency than PEI-PCL/PEG-PCL based nanoparticles at low N/P ratios, higher cellular uptake, and a gene silencing efficiency of around 40% as a result of the higher molecular weight PEI blocks. These results suggested that the PEI-PCL-PEI/PEG-PCL nanoparticle system could be a promising vehicle for siRNA delivery at minimal synthetic effort.”

PEG-PLGA from PolySciTech utilized in development of nanoparticle that modifies tumor microenvironment for improved chemotherapy

Friday, December 2, 2022, 3:33 PM ET

In living systems, cancerous tumors create a unique, local microenvironment by a variety of mechanisms. One of these is the effect of the cancer itself which consumes resources and oxygen faster than the body can provide it leading to areas of low oxygen content. Additionally cancer acts to suppress the immune system in its local area. Often, these unusual conditions surrounding the growing cancer impedes the effects of chemotherapy agents. Recently, researchers at the Chinese Academy of Sciences utilized PEG-PLGA (Cat AK010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) as part of a multifunctional nanoparticle and tested this for its ability to restore the microenvironment of cancer to conditions under which drugs can be more effective. This research holds promise to improve treatments against this often fatal disease. Read more: Li, Lei, Mingming Zhen, Haoyu Wang, Zihao Sun, Xinran Cao, Jie Li, Shuai Liu et al. "Tumor microenvironment-modulated multiple nanotherapeutic system for potent cancer immunotherapy and metastasis inhibition." Nano Today 48 (2023): 101702. https://www.sciencedirect.com/science/article/pii/S1748013222003309

“Highlights: This nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages to reverse immunosuppression, serving for TME reprogramming. This nanotherapeutic system stimulates dendritic cells maturation, thereby initiating T-cell-mediated anti-tumor immune response. The nanotherapeutic system eliminates primary tumor and efficiently inhibits tumor metastasis without obvious adverse effects. The nanotherapeutic system creates superior synergistic cancer immunotherapy combined with anti-PD-L1 immune checkpoint inhibitor. Abstract: The hypoxic and immunosuppressive tumor microenvironment (TME) generally weaken the efficacy of immunotherapy in solid tumors. However, reversing TME remains a formidable challenge. Here, an elaborately multitasking nanotherapeutic system (PEG-PLGA-R848@GFCNs) is demonstrated to forceful remodel TME. This nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages (TAMs) to reverse immunosuppression, serving for TME reprogramming. Furthermore, PEG-PLGA-R848@GFCNs stimulates dendritic cells maturation, thereby initiating T-cell-mediated anti-tumor immune response. Of note, the nanotherapeutic system eliminates primary tumor that established by 4T1 tumor models in mice and efficiently inhibits B16F10 melanoma metastasis without obvious adverse effects. Importantly, PEG-PLGA-R848@GFCNs combined with anti-PD-L1 immune checkpoint inhibitor achieves superior synergistic cancer immunotherapy. Collectively, our work offers a reliable and safe strategy to fabricate a multitasking nanotherapeutic system for comprehensively modulating TME to achieve effective cancer immunotherapy and metastasis inhibition. This multitasking nanotherapeutic system could validly relieve tumor hypoxia and induce M2 to M1 polarization of tumor-associated macrophages to reverse immunosuppression, serving for tumor microenvironment reprogramming, which not only eliminates primary tumor and efficiently inhibit tumor metastasis, but could create superior synergistic cancer immunotherapy combined with anti-PD-L1 immune checkpoint inhibitor. Keywords: Cancer immunotherapy Immunosuppressive tumor microenvironment Tumor hypoxia relief Gado fullerene nanoparticles Immune checkpoint inhibitor”

PLGA from PolySciTech used in development of oral microparticles for localized colon delivery of 5FU as colorectal cancer treatment

Thursday, December 1, 2022, 4:56 PM ET

Under normal oral drug delivery conditions, it is desired for the medicine to be released in the small intestine, or before if it is stable in acid, and to uptake across the lumen into the bloodstream. However, for treating issues located in the colorectal area, better drug delivery is achieved by designing a formulation which delays release beyond the small intestine and delivers the drug directly into the large intestine and colorectal area. This can be utilized to achieve localized delivery to a portion of the body which is not normally the target for localized delivery. Researchers at Pusan National University and Korea University utilized PLGA (AP037) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop chemotherapeutic, 5-FU, loaded microparticles designed to pass through the stomach and intestines before releasing the drug into the colon for targeted treatment of colorectal cancer. This research holds promise to provide for improved treatment against cancer. Read more: Lee, Juho, Junhwan Bae, Dongmin Kwak, Hyunwoo Kim, Jihyun Kim, Shwe Phyu Hlaing, Aruzhan Saparbayeva et al. "5-Fluorouracil crystal-incorporated, pH-responsive, and release-modulating PLGA/Eudragit FS hybrid microparticles for local colorectal cancer-targeted chemotherapy." International Journal of Pharmaceutics (2022): 122443. https://www.sciencedirect.com/science/article/pii/S037851732200998X

“Abstract: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent for colorectal cancer (CRC) owing to its potent anticancer effects. However, severe systemic side effects and poor drug accumulation in the CRC tissues limit its efficacy. This study aimed to develop 5-FU crystal-incorporated, pH-responsive, and release-modulating poly(d,l-lactide-co-glycolide)/Eudragit FS hybrid microparticles (5FU-EPMPs) for the local CRC-targeted chemotherapy. Approximately 150 μm 5FU-EPMPs were fabricated via the S/O/W emulsion solvent evaporation method, with 7.93 ± 0.24% and 87.23 ± 2.64% 5-FU loading and encapsulation efficiencies, respectively. Drug release profiles in a simulated pH environment of the gastrointestinal tract revealed that premature 5-FU release in the stomach and small intestine was prevented, thereby minimizing systemic 5-FU absorption. After reaching the colon, 5-FU was continuously released for >15 h, allowing long-term exposure of CRC tissues to sufficient 5-FU concentrations. Furthermore, in a CRC mouse model, the 5FU-EPMPs showed potent inhibition of tumor growth without signs of systemic toxicity. Thus, the 5FU-EPMPs represent a promising drug delivery system for local CRC-targeted chemotherapy. Keywords: 5-fluorouracil pH-responsive release modulation colorectal cancer colon-targeted delivery local chemotherapy.”

PLGA-PEG-Mal, PLGA-CY5 from PolySciTech used in development of triple-negative breast-cancer targeting nanoparticles

Tuesday, November 22, 2022, 9:45 AM ET

Cancer is a widely diverse set of disease states with a single moniker to describe, in general, any overgrowth of human tissue. Because of their diversity, the method to treat the cancer must be optimized to the exact type of cancer. Most types of breast cancer respond well to modern therapy based on their specific markers. For example, most HER2+ type breast cancers respond well to treatments utilizing herceptin which targets the HER2 receptor. However, a form of breast cancer which lacks the three most common receptors, so called “triple-negative” breast cancer is very difficult to treat as these conventional therapies are ineffective to that particular type of cancer. Recently, researchers at University of Maryland utilized Methoxy-terminated PLGA−PEG (10:5 kDa) (Cat# AK010), PLGA−PEG with maleimide end group (PLGA−PEGMal, 10:5 kDa) (Cat# AI053), and PLGA-Cyanine 5 (PLGA-Cy5, 30−55 kDa) (Cat# AV034) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create fn-14 targeted nanoparticles for therapy against triple-negative breast cancer that has metastasized into the brain. This research holds promise to improve therapies against this very difficult to treat form of cancer. Read more: Carney, Christine P., Anshika Kapur, Pavlos Anastasiadis, Rodney M. Ritzel, Chixiang Chen, Graeme F. Woodworth, Jeffrey A. Winkles, and Anthony J. Kim. "Fn14-Directed DART Nanoparticles Selectively Target Neoplastic Cells in Preclinical Models of Triple-Negative Breast Cancer Brain Metastasis." Molecular Pharmaceutics (2022). https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.2c00663

“Triple-negative breast cancer (TNBC) patients with brain metastasis (BM) face dismal prognosis due to the limited therapeutic efficacy of the currently available treatment options. We previously demonstrated that paclitaxel-loaded PLGA–PEG nanoparticles (NPs) directed to the Fn14 receptor, termed “DARTs”, are more efficacious than Abraxane─an FDA-approved paclitaxel nanoformulation─following intravenous delivery in a mouse model of TNBC BM. However, the precise basis for this difference was not investigated. Here, we further examine the utility of the DART drug delivery platform in complementary xenograft and syngeneic TNBC BM models. First, we demonstrated that, in comparison to nontargeted NPs, DART NPs exhibit preferential association with Fn14-positive human and murine TNBC cell lines cultured in vitro. We next identified tumor cells as the predominant source of Fn14 expression in the TNBC BM-immune microenvironment with minimal expression by microglia, infiltrating macrophages, monocytes, or lymphocytes. We then show that despite similar accumulation in brains harboring TNBC tumors, Fn14-targeted DARTs exhibit significant and specific association with Fn14-positive TNBC cells compared to nontargeted NPs or Abraxane. Together, these results indicate that Fn14 expression primarily by tumor cells in TNBC BMs enables selective DART NP delivery to these cells, likely driving the significantly improved therapeutic efficacy observed in our prior work.”

PLGA-NH2 from PolySciTech used in development of polypeptide capped nanoparticles for treatment of ovarian cancer

Tuesday, November 15, 2022, 4:17 PM ET

Active targeting holds great potential for treatment of many disease states including improved drug delivery to cancer cells. In this method a biodegradable nanoparticle is loaded with a active pharmaceutical (drug) and surface modified to provide for selectively sticky ligands which attach to selected sites on cancer cells or in tumors. Recently, researchers at The City University of New York and Icahn School of Medicine, used PLGA-amine (Cat# AI010) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create RGD end capped particles loaded with combretastatin A4. They tested this for treatment against ovarian cancer. This research holds promise to improve therapies against this lethal disease. Read more: Dragulska, Sylwia A., Mina Poursharifi, Ying Chen, Marek T. Wlodarczyk, Maxier Acosta Santiago, Peter Dottino, John A. Martignetti, and Aneta J. Mieszawska. "Engineering and Validation of a Peptide-Stabilized Poly (lactic-co-glycolic) Acid Nanoparticle for Targeted Delivery of a Vascular Disruptive Agent in Cancer Therapy." Bioconjugate Chemistry (2022). https://pubs.acs.org/doi/abs/10.1021/acs.bioconjchem.2c00418

“ABSTRACT: Developing a biocompatible and biodegradable nanoparticle (NP) carrier that integrates drug-loading capability, active targeting, and imaging modality is extremely challenging. Herein, we report an NP with a core of poly(lactic-coglycolic) acid (PLGA) chemically modified with the drug combretastatin A4 (CA4), a vascular disrupting agent (VDA) in clinical development for ovarian cancer (OvCA) therapy. The NP is stabilized with a short arginine-glycine-aspartic acid phenylalanine x3 (RGDFFF) peptide via self-assembly of the peptide on the PLGA surface. Importantly, the use of our RGDFFF coating replaces the commonly used polyethylene glycol (PEG) polymer that itself often induces an unwanted immunogenic response. In addition, the RGD motif of the peptide is well-known to preferentially bind to αvβ3 integrin that is implicated in tumor angiogenesis and is exploited as the NP’s targeting component. The NP is enhanced with an optical imaging fluorophore label via chemical modification of the PLGA. The RGDFFF-CA4 NPs are synthesized using a nanoprecipitation method and are ∼75 ± 3.7 nm in diameter, where a peptide coating comprises a 2−3 nm outer layer. The NPs are serum stable for 72 h. In vitro studies using human umbilical cord vascular endothelial cells (HUVEC) confirmed the high uptake and biological activity of the RGDFFF-CA4 NP. NP uptake and viability reduction were demonstrated in OvCA cells grown in culture, and the NPs efficiently accumulated in tumors in a preclinical OvCA mouse model. The RGDFFF NP did not induce an inflammatory response when cultured with immune cells. Finally, the NP was efficiently taken up by patient-derived OvCA cells, suggesting a potential for future clinical applications.”

New Product: RiPurpose polyethylene terephthalate prepolymer for upcycled, green polymer synthesis

Thursday, November 3, 2022, 12:45 PM ET

Akina, Inc, in partnership with RiKarbon (https://rikarbon.com/) is providing RiPuroposeTM PET prepolymer. You can learn more and see ordering details here https://akinainc.com/polyscitech/products/ripurpose/index.php

RiPurpose Oligomer is produced by the chemical breakdown of post-consumer waste polyethylene terephthalate (PET) plastic collected from the ocean and environment. This sustainable and green co-monomer can be used as a direct replacement for petroleum-derived feedstock to produce high-value renewable and upcycled polymers by polycondensation and transesterification reactions. RiPurpose Olig1000-700 can be directly used as a feedstock during the polycondensation step of PET production, thereby avoiding the esterification step to prepare a prepolymer intermediate. By using this recycled feedstock, customers can claim CO2 emission reduction of up to 60% for their end-use polymers. The material can also be utilized as an initiator for ring-opening polymerization of various monomers, such as caprolactone, which can be used to make PET-co-caprolactone copolymers that can be utilized as compatibilizers in polymer blends. Additionally, polycondensation can be performed with a wide variety of materials to create novel polymeric materials. An example of this is the co-reaction between PET and poly(tetramethylene oxide) which has been reported recently in literature for the creation of versatile multi-blocks segmented poly(ether-ester)s such as poly(ethylene terephthalate-co-1,4-cyclohexanedimethylene terephthalate)-block-poly(tetramethylene oxide) which has highly controlled melt and mechanical properties. Further modification of the polymer can be achieved by initially reacting it with an excess quantity of ethylene glycol under polycondensation to convert the precursor into a di-alcohol endcap product. This can subsequently be reacted with isothiocyanates to form PET-polyurethanes in which case the PET behaves as a chain extender in the stepwise reaction. Similarly, a reaction with diglycidyl compounds can be used for the preparation of epoxies. Conversely, a reaction with excess terephthalic acid can convert into a diacid form. This can subsequently be reacted with diamines in a polycondensation condition to form polyamides. The potential applications for this versatile precursor are diverse and hold great promise for further development. RiPurpose Patent Pending (US Provisional Patent# 63/312519)

PLGA-PEG-PLGA from PolySciTech used in development of gel for treatment of nerve-damage and paralysis

Monday, October 31, 2022, 4:22 PM ET

PLGA-PEG-PLGA is a polymer which can dissolve in cold water and form into a gel at increased temperature and, as such, is referred to as a thermogel. Peripheral nerve injury (PNI) is a significant medical issue occurring in approximately 3% of all trauma patients and often leads to paralysis or malfunction of affected parts of the body. Erythropoietin (EPO) is an endogenous stimulant of vessel growth and can aid in tissue repair by promoting cell proliferation and vasculogenesis. Recently, researchers at Pennsylvania State University and University of Arizona used PLGA-PEG-PLGA (PolyVivo cat# AK097) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create an EPO loaded thermogel and researched the use of this for treatment of PNI. This research holds promise to improve the treatment of PNI and reduce the incidence of nerve-damage induced paralysis. Read more: Manto, Kristen M., Prem Kumar Govindappa, Brandon Martinazzi, Aijie Han, John P. Hegarty, Zachary Koroneos, M. A. Talukder, and John C. Elfar. "Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury." Journal of Nanobiotechnology 20, no. 1 (2022): 1-17. https://jnanobiotechnology.biomedcentral.com/articles/10.1186/s12951-022-01666-5

“Abstract: Background: Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. Methods: In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. Results: EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. Conclusion: This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.42600297927856 seconds)


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