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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FDA-Akina joint publication describes solvent-vapor particle-morphological testing methodology for microstructural analysis

Tuesday, September 20, 2022, 10:14 AM ET

Long-Acting Injectable (LAI) delivery microparticles are complicated structures comprised of both biodegradable polymers, pharmaceutical compounds, and other excipients in a specific configuration so as to achieve the desired delivery profile. These allow for single injections to provide patients with the quantity of drug necessary for pharmaceutical efficacy from weeks up to six-months based on the formulation. Accomplishing this is not a trivial task and, due to their small size, obtaining critical information regarding the nature of the microstructural arrangement of the various components within the particles. To do this, the various components must be selectively altered or removed and the particle analyzed in order to record the change. Recently, Akina’s lab, in cooperation with the Food and Drug Administration via the GDUFA program, developed a methodology to selectively expose particles to semi-solvent vapors and record their changes. This methodology can enable learning more about the structural arrangements within microparticle formulations. Want to learn more about your prototype particles, see more about this and other analysis options here (http://www.akinalytics.com/index.php#home). Read more: Garner, John, Sarah Skidmore, Justin Hadar, Haesun Park, Kinam Park, Bin Qin, and Yan Wang. "Surface analysis of sequential semi-solvent vapor impact (SAVI) for studying microstructural arrangements of poly (lactide-co-glycolide) microparticles." Journal of Controlled Release 350 (2022): 600-612. http://kinampark.com/KPYear/files/2022%20Garner%2C%20Surface%20analysis%20of%20sequential%20semi-solvent%20vapor%20impact%20%28SAVI%29%20for%20studying%20microstructural%20arrangements%20of%20poly%28lactide-co-glycolide%29%20microparticles.pdf

“Abstract: Biodegradable poly(lactide-co-glycolide) (PLGA) microparticles have been used as long-acting injectable (LAI) drug delivery systems for more than three decades. Despite extensive use, few tools have been available to examine and compare the three-dimensional (3D) structures of microparticles prepared using different compositions and processing parameters, all collectively affecting drug release kinetics. Surface analysis after sequential semi-solvent impact (SASSI) was conducted by exposing PLGA microparticles to different semi-solvent in the liquid phase. The use of semi-solvent liquids presented practical experimental difficulties, particularly in observing the same microparticles before and after exposure to semi-solvents. The difficulties were overcome by using a new sequential semi-solvent vapor (SSV) method to examine the morphological changes of the same microparticles. The SASSI method based on SSV is called surface analysis of semi-solvent vapor impact (SAVI). Semi-solvents are the solvents that dissolve PLGA polymers depending on the polymer's lactide:glycolide (L:G) ratio. A sequence of semi-solvents was used to dissolve portions of PLGA microparticles in an L:G ratio-dependent manner, thus revealing different structures depending on how microparticles were prepared. Exposing PLGA microparticles to semi-solvents in the vapor phase demonstrated significant advantages over using semi-solvents in the liquid phase, such as in control of exposure conditions, access to imaging, decreasing the time for sequential exposure of semi-solvents, and using the same microparticles. The SSV approach for morphological analysis provides another tool to enhance our understanding of the microstructural arrangement of PLGA polymers. It will improve our comprehensive understanding of the factors controlling drug release from LAI formulations based on PLGA polymers. (This work was supported by BAA Contract # 75F40119C10096 from the U.S. Food and Drug Administration (FDA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the FDA)”

Polymers from PolySciTech used in study on nanoparticle control by solvent-based nanoprecipitation

Thursday, September 15, 2022, 4:36 PM ET

Nanoparticles are generated by carefully controlling the precipitation of a polymer in a non-solvent condition. The choice of solvents and control of their interactions has a strong impact on nanoparticle size and properties however this has not received as much systematic study as it deserves. Recently, researchers from ETH Zurich utilized mPEG-PDLLa (AK056), mPEG-PLGA (AK037), mPEG-PCL (AK128) from PolySciTech Division of Akina, Inc. (www.polyscitech.com). Read more: Bovone, Giovanni, Lucien Cousin, Fabian Steiner, and Mark W. Tibbitt. "Solvent Controls Nanoparticle Size during Nanoprecipitation by Limiting Block Copolymer Assembly." Macromolecules (2022). https://pubs.acs.org/doi/abs/10.1021/acs.macromol.2c00907

“Abstract: Control of the properties of nanoparticles (NPs), including size, is critical for their application in biomedicine and engineering. Polymeric NPs are commonly produced by nanoprecipitation, where a solvent containing a block copolymer is mixed rapidly with a nonsolvent, such as water. Empirical evidence suggests that the choice of solvent influences NP size; yet, the specific mechanism remains unclear. Here, we show that solvent controls NP size by limiting block copolymer assembly. In the initial stages of mixing, polymers assemble into dynamic aggregates that grow via polymer exchange. At later stages of mixing, further growth is prevented beyond a solvent-specific water fraction. Thus, the solvent sets NP size by controlling the extent of dynamic growth up to growth arrest. An a priori model based on spinodal decomposition corroborates our proposed mechanism, explaining how size scales with the solvent-dependent critical water fraction of growth arrest and enabling more efficient NP engineering.”

Fluorescently-labelled PLGA from PolySciTech used in development of siRNA delivery spheroplexes for ulcerative colitis treatment

Friday, September 9, 2022, 10:10 AM ET

siRNA is short snippets of RNA that bind to transcribed messenger RNA and prevent it from being translated into a protein. This allows siRNA to “silence” select genetic expression and prevent the formation of proteins which may be pathological in nature. Recently, researchers at Universidade Federal de Minas Gerais (Brazil), PSL University, Sorbonne Université, Université de Lyon, and INSERM (France), used fluorescent PLGA-FPR648 (cat# AV008) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create siRNA loaded spheroplexes. The Fluorescent polymer allowed for tracking of the nanoparticles for research applications. This research holds promise to improve siRNA delivery for gene therapy as ulcerative colitis treatment. Read More: Arruda, D.C., Lachagès, A.M., Demory, H., Escriou, G., Lai-Kuen, R., Dugas, P.Y., Hoffmann, C., Bessoles, S., Sarrabayrouse, G., Malachias, A. and Finet, S., 2022. Spheroplexes: Hybrid PLGA-cationic lipid nanoparticles, for in vitro and oral delivery of siRNA. Journal of Controlled Release, 350, pp.228-243. https://www.sciencedirect.com/science/article/pii/S0168365922005351

“Highlights: Spheroplexes (Sphx) were developed by a modified nanoprecipitation method using siRNA lipoplexes as starting nanoparticles. Sphx were spherical nanoparticles with surface characteristics similar to those of lipoplexes. Sphx were very stable particles and more efficient than siRNA lipoplexes for the in vitro delivery of siRNA. Sphx were uptake by macrophages/monocytes at the colon with nearly no toxicity after oral administration. The oral delivery of TNF-α siRNAs Sphx to mice with ulcerative colitis reduced the level of TNF-α and signs of lesions. Abstract: Vectorized small interfering RNAs (siRNAs) are widely used to induce gene silencing. Among the delivery systems used, lipid-based particles are the most effective. Our objective was the development of novel lipid-polymer hybrid nanoparticles, from lipoplexes (complexes of cationic lipid and siRNAs), and poly (lactic-co-glycolic acid) (PLGA), using a simple modified nanoprecipitation method. Due to their morphology, we called these hybrid nanoparticles Spheroplexes. We elucidated their structure using several physico-chemical techniques and showed that they are composed of a hydrophobic PLGA matrix, surrounded by a lipid envelope adopting a lamellar structure, in which the siRNA is complexed, and they retain surface characteristics identical to the starting nanoparticles, i.e. lipoplexes siRNA. We analyzed the composition of the particle population and determined the final percentage of spheroplexes within this population, 80 to 85% depending on the preparation conditions, using fluorescent markers and the ability of flow cytometry to detect nanometric particles (approximately 200 nm). Finally, we showed that spheroplexes are very stable particles and more efficient than siRNA lipoplexes for the delivery of siRNA to cultured cells. We administered spheroplexes contain siRNAs targeting TNF-α to mice with ulcerative colitis induced by dextran sulfate and our results indicate a disease regression effect with a response probably mediated by their uptake by macrophages / monocytes at the level of lamina propria of the colon. The efficacy of decreased level of TNF-α in vivo seemed to be an association of spheroplexes polymer-lipid composition and the specific siRNA. These results demonstrate that spheroplexes are a promising hybrid nanoparticle for the oral delivery of siRNA to the colon. Keywords: RNA interference Lipoplexes Hybrid nanoparticle Delivery system Biodegradable polymer Oral delivery”

PLA and PCL from PolySciTech used in development of opioid abuse deterrent system to prevent smoking of thebaine

Friday, September 9, 2022, 10:09 AM ET

Opioids provide for pain relief however, due to narcotic and addictive effects, are widely misused and abused. Systems which discourage misuse of opioids by seeking alternate routes of intake (i.e. smoking or injecting components from pills that are meant to be injested) than the prescribed method can reduce opportunites for misuse. Recently, Researchers at Purdue University used PLA (cat# AP006) and PCL (cat# AP257) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create a microsphere formulation to combine in with oral doses of opioids which make smoking the tablets impractical. Read more: Vasiukhina, Anastasiia, Sheryhan F. Gad, Elyssia N. Wellington, Danielle M. Wilmes, Yoon Yeo, and Luis Solorio. "PLA-PCL Microsphere Formulation to Deter Abuse of Prescription Opioids by Smoking." International Journal of Pharmaceutics (2022): 122151. https://www.sciencedirect.com/science/article/pii/S0378517322007050

“Abstract: Opioids are commonly prescribed across the United States (US) for pain relief, despite their highly addictive nature that often leads to abuse and overdose deaths. Abuse deterrent formulations (ADFs) for prescription opioids make the non-therapeutic use of these drugs more difficult and less satisfying. Although approximately one-third of surveyed abusers in the US reported smoking opioids, to our knowledge, no commercialized ADF effectively prevents opioid smoking. Here, we report a novel approach to deter smoking of a model prescription opioid drug, thebaine (THB), by using polymer blend microspheres (MS) comprising polylactic acid (PLA) and polycaprolactone (PCL). We utilized high-performance liquid chromatography (HPLC) and thermogravimetric analysis (TGA) to test the ability of PLA-PCL MS to limit the escape of vaporized THB. Additionally, we compared the abuse-deterrent potential of PLA-PCL MS to that of activated carbon (AC) and mesoporous silica (MPS), two materials with excellent drug-adsorbing properties. Our MS formulation was effective in reducing the amount of both active drug and thermal degradation products in the vapor generated upon heating of THB. These results support that PLA-PCL microspheres can be co-formulated in a tablet with common prescription opioids to deter their abuse via the smoking route.”

PLGA-PEG-COOH and from PolySciTech Division of Akina, Inc. used in development of sialyl targetted nanoparticles for gastric cancer treatment

Friday, September 9, 2022, 10:08 AM ET

Gastric cancer accounts for about 783,000 deaths each year (Rawla, 2019; Prz Gastroenterol. 2019; 14(1): 26–38.) and can be difficult to treat based on how the cancer has spread through the system. Recently, researchers at Universidade do Porto and CESPU-IUCS (Portugal) utilized PLGA-PEG-COOH (Cat# AI076) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create sialyl targetting nanoparticles to attach to epithelial tumors such as those in gastric cancer. This research holds promise to improve therapies against this disease. Read more: Diniz, Francisca, Maria Azevedo, Flávia Sousa, Hugo Osório, Diana Campos, Paula Sampaio, Joana Gomes, Bruno Sarmento, and Celso A. Reis. "Polymeric Nanoparticles Targeting Sialyl-Tn in Gastric Cancer: A Live Tracking Under Flow Conditions." Materials Today Bio (2022): 100417. https://www.sciencedirect.com/science/article/pii/S2590006422002150

“Abstract: Drug delivery using nanoparticles (NPs) represents a potential approach for therapy in cancer, such gastric cancer (GC) due to their targeting ability and controlled release properties. The use of advanced nanosystems that deliver anti-cancer drugs specifically to tumor cells may strongly rely on the expression of cancer-associated targets. Glycans aberrantly expressed by cancer cells are attractive targets for such delivery strategy. Sialylated glycans, such as Sialyl-Tn (STn) are aberrantly expressed in several epithelial tumors, including GC, being a potential target for a delivery nanosystem. The aim of this study was the development of NPs surface-functionalized with a specific antibody targeting the STn glycan and further evaluate this nanosystem effectiveness regarding its specificity and recognition capacity. Our results showed that the NPs surface-functionalized with anti-STn antibody efficiently are recognized by cells displaying the cancer-associated STn antigen under static and live cell monitoring flow conditions. This uncovers the potential use of such NPs for drug delivery in cancer. However, flow exposure was disclosed as an important biomechanical parameter to be taken into consideration. Here we presented an innovative and successful methodology to live track the NPs targeting STn antigen under shear stress, simulating the physiological flow. We demonstrate that unspecific binding of NPs agglomerates did not occur under flow conditions, in contrast with static assays. This robust approach can be applied for in vitro drug studies, giving valuable insights for in vivo studies. Keywords: Polymeric nanoparticles Gastric cancer Sialyl-Tn antigen Microfluidics”

PEG-PLGA from PolySciTech used in development of oral peptide delivery system for anti-inflammatory applications

Wednesday, August 24, 2022, 9:14 AM ET

Typically, peptides (shorter versions of proteins) can not be readily delivered as an oral formulation such as tablet or solution because most peptides are destroyed in the stomach and have poor transportation across the intestinal lining. This is unfortunate as peptide-based drugs are quite effective against a range of disease states and opening up more routes of administration can improve their application range. Recently, researchers at The University of Queensland (Australia) utilized mPEG-PLGA (cat# AK026) from PolySciTech division of Akina (www.polyscitech.com) to develop nanoparticles for oral delivery of anti-inflammatory peptides. This research holds promise to improve therapeutic routes for peptide delivery. Read more: Xu, Weizhi, Vinod Kumar, Cedric S. Cui, Xaria X. Li, Andrew K. Whittaker, Zhi Ping Xu, Maree T. Smith, Trent M. Woodruff, and Felicity Y. Han. "Success in navigating hurdles to oral delivery of a bioactive peptide complement antagonist through use of nanoparticles to increase bioavailability and in vivo efficacy." Advanced Therapeutics (2022): 2200109. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202200109

“Abstract: Substantial preclinical data have validated cyclic hexapeptide, complement C5a receptor 1 antagonists (C5aRAs) that target immune cells as novel treatments for a range of inflammatory diseases which currently have limited effective treatment options. However, like most small-molecule peptides, their poor oral bioavailability and short circulation half-life are major hurdles that have limited their clinical translation. Here, a single emulsion technique was employed to produce poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with exceptionally high peptide C5aRA (PMX205) loading efficiency (over 50%). Strikingly, the PMX205-NPs not only facilitated prolonged release of the encapsulated PMX205 but also dramatically increased its oral bioavailability (from ∼25% to ∼50%), and therapeutic potential (∼ 95% inhibition of C5a induced neutrophilia in mice and maintenance of neuroprotective barrier integrity). The enhanced in vivo pharmacological activity of PMX205 in the form of NPs opens an exciting opportunity for the clinical application of peptide C5aRAs and possibly other therapeutic peptides. Keywords: C5aR1 antagonists (C5aRAs); bioactive peptide; nanoparticles (NPs); poly(lactic-coglycolic) acid (PLGA); oral bioavailability; pharmacokinetics and blood-brain barrier.”

PLGA-PEG-COOH from PolySciTech used in development of monoclonal antibody delivery system for heart-disease treatment

Wednesday, August 17, 2022, 2:01 PM ET

Atherosclerosis (heart disease) is a common cause of death characterized by lesions which act to block blood flow through blood vessels in the heart. Part of the cause is overexpression of fibronectin components which lead to extensive remodeling and tissue ingrowth into the vessel lumen. Recently researchers at University of Genoa (Italy) and Universidade do Porto (Portugal) utilized (PLGA-PEG-COOH, Cat# AI076) from PolySciTech division of Akina (www.polyscitech.com) to develop nanoparticles for delivery of Bevacizumab labelled with immunouteroglobin for targeted delivery. This research holds promise to improve treatments of heart disease in the future. Read more: Atanasio, Giulia De Negri, Pier Francesco Ferrari, Ana Baião, Patrizia Perego, Bruno Sarmento, Domenico Palombo, and Roberta Campardelli. "Bevacizumab encapsulation into PLGA nanoparticles functionalized with immunouteroglobin-1 as an innovative delivery system for atherosclerosis." International Journal of Biological Macromolecules (2022). https://www.sciencedirect.com/science/article/pii/S0141813022017639

“Abstract: Atherosclerosis represents one of the main causes of death in the Western world. It is a multifactorial pathology characterized by lesions that reduce the lumen of the vessels causing serious clinical events. The extradomain-B of fibronectin is overexpressed during angiogenesis and in tissues undergoing growth and extensive remodeling, i.e., atherosclerotic plaque. Bevacizumab is a recombinant humanized monoclonal antibody that can play a role against the angiogenesis process reducing the risk associated with this process in atherosclerosis. In this work, an innovative drug delivery device for target delivery of bevacizumab to the atherosclerotic lesion is proposed. A production protocol for poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles loaded with bevacizumab and functionalized with immunouteroglobin-1 was designed. Once immunouteroglobin-functionalized nanoparticles were produced, they were characterized regarding morphology, mean diameter, ζ-potential, association and conjugation efficiencies, bevacizumab release profile both in phosphate buffered saline and in serum, bevacizumab stability after release, cytocompatibility, and hemocompatibility. Nanoparticle mean diameter was in the range of 217–265 nm, their surface charge was between −21 and − 8 mV, and the association and conjugation efficiency of about 76 and 59 %, respectively. Fourier transform infrared spectroscopy analysis confirmed the functionalization of their surface with immunouteroglobin-1. In vitro assays showed that the studied nanoparticles were cytocompatible, once in contact with human endothelial and murine macrophages cell line up to 72 h, and hemocompatible, once in contact with red blood cells, at different concentrations of encapsulated BEV (0.1, 1, 10, and 100 μgBEV/mL).”

PLGA-Cy5 labelled polymer from PolySciTech used in development of anti-inflammatory treatment of spinal cord injury

Wednesday, August 17, 2022, 2:00 PM ET

One of the problems post spinal-cord injury is that inflammation (swelling, etc.) complicates and prevents the healing process. Targetted delivery of MAPK-activated protein kinase-2 (MK2) inhibitor can reduce the damaging effects of this inflammation. Recently researchers at Houston Methodist Academic Institute utilized PLGA-CY5 fluorescent (Cat# AV034) polymer from PolySciTech division of Akina (www.polyscitech.com) to create fluorescent nanoparticles for tracking purposes. This research holds promise to improve therapeutic outcomes for cpinal cord injury and reduce the incidence of associated paralysis. Read more: Stigliano, Cinzia, Allison Frazier, and Philip J. Horner. "Modulation of Neuroinflammation Via Selective Nanoparticle‐Mediated Drug Delivery to Activated Microglia/Macrophages in Spinal Cord Injury." Advanced Therapeutics: 2200083. https://onlinelibrary.wiley.com/doi/abs/10.1002/adtp.202200083

“Abstract: Inflammation after spinal cord injury (SCI) is characterized by immune cell invasion and activation, combined with inflammatory mediator release that worsens outcomes following primary trauma. Effective therapies targeting neuroinflammation remain an unmet need, and modulation of the injury microenvironment to induce a comprehensive pro-regenerative response is an attractive therapeutic approach. Given its crucial role in cell stress and inflammation after SCI, we focused on the potential of pharmacologically targeting MAPK-activated protein kinase-2 (MK2) to modulate the response of microglia/macrophages after injury. We developed nanoparticles (NPs) containing an MK2 inhibitor for specific targeting of microglia/macrophages. NPs selectively targeted and modulated activated microglia/macrophages in vitro and in a rat model of SCI. NPs in the acute injury setting reduced the pro-inflammatory cytokine IL-6 and increased the anti-inflammatory cytokine IL-10. Importantly, NPs had a significant effect on microglia/macrophage distribution and accumulation, leading to an ∼65% reduction of immune cells around the injury. Lastly, microglia/macrophage populations with activated morphology were significantly reduced compared to resting or ramified cells around the lesion site. Our strategy exhibits potential therapeutic efficiency and specificity for local, pharmacologic manipulation of activated microglia/macrophages, and is a versatile tool to manage acute inflammation and glia plasticity after central nervous system trauma.”

New Product: Polysuccinimide.

Wednesday, August 17, 2022, 1:59 PM ET

PolySciTech Division of Akina, Inc. has added a versatile new product to the catalog, AI235 (https://akinainc.com/polyscitech/products/polyvivo/catalogue.php?highlight=AI235#h) is a ~ 30 kDa polysuccinimide precursor which reacts with either water to form poly(aspartic acid) or amine-bearing compounds to form side-chain poly(aspartamide) compounds. Both reactions can be conducted easily at to form a wide range of potential products from this versatile precursor. Find out what you can do with this in your lab today.

PLCL from PolySciTech: Akina used in development of nanoparticles for delivery of SN-38 as colorectal cancer therapy

Wednesday, August 3, 2022, 4:42 PM ET

Colon cancer is statistically the third most fatal malignancy worldwide. Almost 50% of patients develop metastatic colon cancer which is a highly fatal condition. Recently, researchers at University of Prishtina (Kosovo), TardigradeNano LLC (California), and San Diego State University used PLCL (cat# AP103) from PolySciTech division of Akina (www.polyscitech.com) along with pluronic to formulate a series of nanoparticles containing SN-38. They tracked the effects of these particles on the gene regulation of colorectal cancer cells with nanoparticles that have a wide pluronic corona or a collapsed one. This study holds promise to improve nanoparticle therapies of cancer in the future. Read more: Koliqi, Rozafa, Arlinda Daka Grapci, Pranvera Breznica Selmani, and Vuk Uskoković. "Gene Expression Effects of the Delivery of SN-38 via Poly (DL-lactide-co-caprolactone) Nanoparticles Comprising Dense and Collapsed Poloxamer Coronae." Journal of Pharmaceutical Innovation (2022): 1-9. https://link.springer.com/article/10.1007/s12247-022-09672-8

“Purpose: SN-38 is an antineoplastic drug with a three orders of magnitude higher activity than its prodrug, irinotecan, a common chemotherapeutic of choice in the treatment of colorectal cancer. A considerable number of genes are known to alter their expression under the influence of free SN-38, but no studies have looked at the gene expression effects of SN-38 delivered via poly(D-L-lactide-co-caprolactone) (PLCL) nanoparticles yet. Method: We evaluated changes to expression levels of genes encoding for ubiquitin D (UBD), fibroblast growth factor 3 (FGF3), histone (HIST), and regulator of cell cycle (RGCC) in SW-480 colon cancer cells in response to free SN-38 and two types of poloxamer-coated PLCL (PEO-PPO-PEO/PLCL) nanoparticles as carriers for SN-38, containing different conformations of the hydrophilic stealth corona: dense or collapsed. Results: Both the free drug and the two drug-loaded nanoformulations upregulated UBD and RGCC and downregulated FGF3 and HIST, which was consistent with the pharmacological activity of SN-38. Still, there was a clear difference in gene expression levels in SW-480 cells depending on whether they were challenged with free SN-38 or with nanoparticles loaded with SN-38. Most critically, the delivery of SN-38 with the nanoparticles prolonged its mode of action and, in the case of genes such as UBD, FGF3, and HIST, provided for a more intense effect on gene expression alteration than that achieved by the drug alone. Conclusions: Nanoparticles comprising the collapsed PEO-PPO-PEO corona produced a more intense effect on gene expression alteration than the nanoparticles with the dense PEO-PPO-PEO corona.”

PLA from PolySciTech:Akina used in development of inulin-PLA copolymer for cancer therapy

Wednesday, July 27, 2022, 3:47 PM ET

While poly(ethylene glycol) is commonly applied to create long-circulating nanoparticles, certain patients develop PEG allergic reactions requiring alternative options. Recently, researchers at University of Salerno (Italy) PLA (cat# AP005, AP231) and mPEG-PLA (cat# AK009) from PolySciTech division of Akina (www.polyscitech.com) to develop long-circulating nanoparticles for drug delivery applications. This research holds promise to improve development of nanotherapies in the future. Read more: Sardo, Carla, Teresa Mencherini, Carmela Tommasino, Tiziana Esposito, Paola Russo, Pasquale Del Gaudio, and Rita Patrizia Aquino. "Inulin-g-poly-D, L-lactide, a sustainable amphiphilic copolymer for nano-therapeutics." Drug Delivery and Translational Research (2022): 1-17. https://link.springer.com/article/10.1007/s13346-022-01135-4

“Cancer therapies started to take a big advantage from new nanomedicines on the market. Since then, research tried to better understand how to maximize efficacy while maintaining a high safety profile. Polyethylene glycol (PEG), the gold standard for nanomedicines coating design, is a winning choice to ensure a long circulation and colloidal stability, while in some cases, patients could develop PEG-directed immunoglobulins after the first administration. This lead to a phenomenon called accelerated blood clearance (ABC effect), and it is correlated with clinical failure because of the premature removal of the nanosystem from the circulation by immune mechanism. Therefore, alternatives to PEG need to be found. Here, looking at the backbone structural analogy, the hydrophilicity, flexibility, and its GRAS status, the natural polysaccharide inulin (INU) was investigated as PEG alternative. In particular, the first family of Inulin-g-poly-D,L-lactide amphiphilic copolymers (INU-PLAs) was synthesized. The new materials were fully characterized from the physicochemical point of view (solubility, 1D and 2D NMR, FT-IR, UV–Vis, GPC, DSC) and showed interesting hybrid properties compared to precursors. Moreover, their ability in forming stable colloids and to serve as a carrier for doxorubicin were investigated and compared with the already well-known and well-characterized PEGylated counterpart, polyethylene glycol-b-poly-D,L-lactide (PEG-PLA). This preliminary investigation showed INU-PLA to be able to assemble in nanostructures less than 200 nm in size and capable of loading doxorubicin with an encapsulation efficiency in the same order of magnitude of PEG-PLA analogues.”

PCL from PolySciTech:Akina used in development of long-acting monoclonal antibody delivery system.

Wednesday, July 27, 2022, 3:44 PM ET

Monoclonal antibodies, or mAbs, are a type of protein made in a laboratory to fight a particular infection (SARS-CoV-2 or certain cancers). These are difficult to deliver due to their tendency to denature. Recently, researchers at University of Cincinnati used PCL (Cat# AP011) from PolySciTech division of Akina (www.polyscitech.com) to develop long-acting anti-body releasing porous implant. This research holds promise to improve the use of this class of pharmaceuticals. Read More: Waterkotte, Thomas, Xingyu He, Apipa Wanasathop, S. Kevin Li, and Yoonjee C. Park. "Long-term Antibody Release Polycaprolactone (PCL) Capsule and the Release Kinetics In Natural and Accelerated Degradation." bioRxiv (2022). https://www.biorxiv.org/content/10.1101/2022.06.06.493286.abstract

“Although therapy using monoclonal antibodies (mAbs) has been steadily successful over the last 20 years, the means of delivery of mAbs has not been optimized, especially for long-term delivery. Frequent injections or infusions have been current standard of care. In this study, we have developed a long-term antibody biodegradable implant using a porous polycaprolactone (PCL) capsule. It released Bevacizumab (Bev) slowly for 8 months to date. The Bev release kinetics fit a drug release model with experimental data of the diffusion coefficient and partition coefficient through the polymer capsule. Since screening drug release profiles for the long-term (> 6 months) is time consuming, an accelerated degradation method was used after validating characteristics of the PCL capsule in natural and accelerated degradation conditions. The correlation of time period between the natural and the accelerated degradation was determined. Overall, the study suggests mAbs can be released from a porous PCL capsule without an effect of the polymer degradation over the long period (~ 6 months) and the long-term release kinetics can be determined by the accelerated degradation within 14 days.”

PLGA-Rhodamine from PolySciTech used in development of arthritis treatment

Wednesday, July 27, 2022, 3:43 PM ET

Osteoarthritis is the most common form of arthritis, affecting millions of people worldwide. It occurs when the protective cartilage that cushions the ends of the bones wears down over time. Recently, researchers at Chungnam National University, Seoul National University and Chungbuk National University (Korea) utilized PLGA-Rhodamine (Cat# AV011) from PolySciTech division of Akina (www.polyscitech.com) to make traceable nanoparticles for tracking the particle location as part of development of osteoarthritis treatment. This research holds promise to improve treatment against arthritis. Read more: Park, Hyewon, Ha-Reum Lee, Hyo Jung Shin, Ji Ah Park, Yongbum Joo, Sun Moon Kim, Jaewon Beom, Seong Wook Kang, Dong Woon Kim, and Jinhyun Kim. "p16INK4a-siRNA nanoparticles attenuate cartilage degeneration in osteoarthritis by inhibiting inflammation in fibroblast-like synoviocytes." Biomaterials Science (2022). https://pubs.rsc.org/en/content/articlehtml/2022/bm/d1bm01941d

“In osteoarthritis (OA), chondrocytes in cartilage undergo phenotypic changes and senescence, restricting cartilage regeneration and favoring disease progression. Although senescence biomarker p16INK4a expression is known to induce aging by halting the cell cycle, therapeutic applications for p16INK4a targeting are limited. Here, we aimed to reduce cartilage damage and alleviate pain using p16INK4a nanoparticles in OA. The p16INK4a expression of human OA chondrocytes and synoviocytes from patients with knee OA was measured and the levels of p16INK4a, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and matrix metalloproteinase (MMP) 13 were examined. p16INK4a siRNA was encapsulated into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and characterized. The partial medial meniscectomy (pMMx) model was performed for the OA model which was investigated by molecular analysis and behavioral tests. The expression of p16INK4a was increased in the synovium and articular cartilage from OA patients. p16INK4a siRNA-loaded PLGA nanoparticles (p16 si_NP) reduced the levels of TNF-α, IL-1β, and IL-6 especially in fibroblast-like synoviocytes (FLSs), and MMP13 in chondrocytes. Rhodamine-tagged NPs injected into the mouse knee joints were found mainly in the synovium. p16 si_NP injection in the pMMx model alleviated pain-associated behavior, and reduced cartilage damage and p16INK4a in the synovium, and MMP13, collagen X, and NITEGE in cartilage. The preferential reduction of p16INK4a in FLSs by the application of RNAi nanomedicine could contribute to the recovery of osteoarthritic cartilage and relieve pain, suggesting that p16INK4a may be a viable future therapeutic candidate.”

PLA from PolySciTech used in development of treatment of gastroschisis

Wednesday, July 27, 2022, 3:42 PM ET

Reported gastroschisis has increased over the past 25 years from 0.1 cases per 10,000 to 1 case per 10,000 live births in developed countries, and from 3 to 5 cases per 10,000 births in developing countries. Recently, researchers from Universitas Airlangga (Indonesia) utilized PLLA (cat# AP006) from PolySciTech division of Akina (www.polyscitech.com) to develop spring-loaded drug delivery systems for treatment of gastroschisis. This research holds promise to improve treatments against this birth defect. Read more: Widiyanti, Prihartini, Fahreza Rachmat Yoviansyah, and Djony Izak Rudyarjo. "Poly L-Lactic Acid (Plla)-Collagen Coating Chitosan as a Spring-Loaded Silo Candidate for Gastroschisis." Journal of International Dental and Medical Research 15, no. 2 (2022): 950-955. http://www.jidmr.com/journal/wp-content/uploads/2022/06/77-MD22_1740_Prihartini_Widiyanti_Indonesia.pdf

“Abstract: Gastroschisis is one of the birth defects with organ conditions that come out of the abdominal cavity. The handling of gastroschisis is conducted by the staged closure method or wrapping the organ that comes out to be inserted slowly using gravity and a spring-loaded silo. To overcome this problem, a research study was conducted to find candidates for spring loaded silos with the combination of 5% PLLA, collagen with various concentrations (1, 0.75, 0.5, and 0.25)%, and 1% chitosan which was expected to reduce the risk of side effects in infants with gastroschisis such as infections and microbes. It can also improve the mechanical properties of the spring-loaded silo membrane. Based on the FTIR test, it showed the functional groups of PLLA (Ester), Collagen (Amide), and Chitosan (Amine). The SEM results showed that the overall pore value was 4.42-6.67 µm, thus it can meet the goretex pore size with a pore size range of 0-25 µm. The results of the tensile strength test, the UTS value on the abdominal wall was 2 - 9.2 MPa, thus the K2 sample with a value of 8.56 MPa has met and the value of the Elasticity Modulus of the linear alba layer on the abdominal wall was 23 - 335 MPa. The results of the contact angle test showed that the PLLA-Collagen chitosan coating samples were better on hydrophilic properties than the PLLA-Collagen samples. Cytotoxicity test results showed that the percentage of living cells was above 70% thus the membrane was non-toxic.”

PLGA from PolySciTech used in development of inhalable tuberculosis treatment

Wednesday, July 27, 2022, 3:40 PM ET

Tuberculosis is a potentially serious infectious disease that mainly affects the lungs. The bacteria that cause tuberculosis are spread from person to person through tiny droplets released into the air via coughs and sneezes. Recently, researchers at Indian Institute of Science used PLGA (cat# AP041) from PolySciTech division of Akina (www.polyscitech.com) to make cationic nanoparticles loaded with rifampicin to target tuberculosis infected mammalian cells. This research holds promise to provide for improved therapies against tuberculosis in the future. Read more: Sharma, Pallavi Raj, Ameya Atul Dravid, Yeswanth Chakravarthy Kalapala, Vishal K. Gupta, Sharumathi Jeyasankar, Avijit Goswami, and Rachit Agarwal. "Cationic inhalable particles for enhanced drug delivery to M. tuberculosis infected macrophages." Biomaterials Advances 133 (2022): 112612. https://www.sciencedirect.com/science/article/pii/S0928493121007529

“Highlights: Mycobacterium tuberculosis infected macrophages are highly phagocytic. Surface charge of PLGA microparticles modified by conjugating poly-l-lysine. Cationic microparticles were taken up rapidly and in large numbers by macrophages. Rifampicin encapsulation in cationic particles improved its intracellular delivery. Enhanced uptake by immune cells and alveolar macrophages in vivo. Abstract: Inhalable microparticle-based drug delivery platforms are being investigated extensively for Tuberculosis (TB) treatment as they offer efficient deposition in lungs and improved pharmacokinetics of the encapsulated cargo. However, the effect of physical parameters of microcarriers on interaction with Mycobacterium tuberculosis (Mtb) infected mammalian cells is underexplored. In this study, we report that Mtb-infected macrophages are highly phagocytic and microparticle surface charge plays a major role in particle internalization by infected cells. Microparticles of different sizes (0.5–2 μm) were internalized in large numbers by Mtb-infected THP-1 macrophages and murine primary Bone Marrow Derived Macrophages in vitro. Drastic improvement in particle uptake was observed with cationic particles in vitro and in mice lungs. Rapid uptake of rifampicin-loaded cationic microparticles allowed high intracellular accumulation of the drug and led to enhanced anti-bacterial function when compared to non-modified rifampicin-loaded microparticles. Cytocompatibility assay and histological analysis in vivo confirmed that the formulations were safe and did not elicit any adverse reaction. Additionally, pulmonary delivery of cationic particles in mice resulted in two-fold higher uptake in resident alveolar macrophages compared to non-modified particles. This study provides a framework for future design of drug carriers to improve delivery of anti-TB drugs inside Mtb-infected cells.”

PEG-PCL and PEG-PLA from PolySciTech used to understand protein – block copolymer micelle interactions

Wednesday, July 6, 2022, 12:51 PM ET

Block copolymers (PEG-PLGA, PEG-PCL, PEG-PLA, etc.) are commonly used to create drug-delivery platforms as they self-form into micelles which can entrap and carry hydrophobic drugs. Like all chemicals, these structures have a complex interaction with the multitude of components present in human blood which leads to their eventual disruption however exactly 'how' this happens is not well known. Recently, researchers at University of Illinois, Chicago used PEG-PCL (cat# AK073) and PEG-PLA (cat# AK009) from PolySciTech division of Akina, Inc. (www.polyscitech.com) to create micelles and investigated their interactions with serum albumins. This research holds promise to provide fundamental understanding to aid in the further development of micelle-based delivery systems. Read more: Dial, Catherine F., and Richard A. Gemeinhart. "Biophysical Characterization of Interactions between Serum Albumin and Block Copolymer Micelles." ACS Biomaterials Science & Engineering (2022). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.2c00016

“Block copolymer micelles have demonstrated great promise in the solubilization of hydrophobic drugs, but an understanding of the blood stability of the drug-laden micelles is needed for therapeutic advancement of micelle technologies. Following intravenous administration, mPEG-CL and mPEG-LA micelles have demonstrated quick release of their cargo and disassembly in blood, but the prevailing mechanisms of micelle disruption and key biomacromolecules driving this disruption have yet to be elucidated. Although protein interactions with solid polymeric nanoparticles have been characterized, not much is known regarding protein interactions with dynamic block copolymer micelles. Herein, we characterize the interaction of bovine and human serum albumins (BSA and HSA) with polymeric micelles, mPEG-CL and mPEG-LA, using protein fluorescence, isothermal titration calorimetry (ITC), and circular dichroism (CD) spectroscopy. We find that BSA and HSA have interactions with mPEG-CL, while only HSA is observed to weakly interact with mPEG-LA. Protein fluorescence suggests that binding of HSA to mPEG-CL and mPEG-LA is driven by electrostatic interactions. ITC suggests an interaction between serum albumin and mPEG-CL block copolymers driven by hydrogen bonding and electrostatic interactions in physiological MOPS-buffered saline, while mPEG-LA has no measurable interaction with either of the serum albumins. CD spectroscopy demonstrates that the protein secondary structure is intact in both proteins in the presence of mPEG-CL and mPEG-LA. Overall, BSA is not always predictive of polymeric interactions with HSA. Understanding of interactions between serum proteins and block copolymer micelles and the exact mechanisms of destabilization will direct the rational design of block copolymer systems for improving blood stability. KEYWORDS: micelle polymer albumin interactions protein−polymer interactions”

PLGA Inherent Viscosity to Molecular Weight Correlation charts

Wednesday, July 6, 2022, 11:21 AM ET

The below charts are from a historical screen clipping of the Lactel(R) Absorbable Polymers provided data correlating IV to Mw prior to their buyout and closure. This is being shown for customer reference in case a customer is looking to purchase a polymer with molecular weight similar to that defined by inherent viscosity though Akina makes no claims regarding the information provided here.

PLGA from PolySciTech used in research on vaccine delivery

Wednesday, June 29, 2022, 2:00 PM ET

Vaccines can be leveraged as a life-saving technology against a wide variety of diseases. There are many mechanisms to provide vaccines and the mode of application drives efficacy. Recently, PLGA from PolySciTech (www.polyscitech.com) was utilized by researchers at Massachusetts Institute of Technology to to investigate microneedle delivery of vaccines. This research holds promise to improve disease prevention in the future. Read more: Sarmadi, Morteza. "Microscale polymeric-based technologies for controlled vaccine delivery." PhD diss., Massachusetts Institute of Technology, 2022. https://dspace.mit.edu/handle/1721.1/143281

“ABSTRACT: Outbreak of infectious diseases such as COIVD-19 is one of the most critical challenges threatening global health and economy, particularly in developing world. Technologies that can improve delivery, access, effectiveness, and stability of vaccination, as a promising tool against outbreaks, would be strategic tools to potentially save lives and avoid trillions of dollars in financial losses. Our group has been developing such platform technologies for controlled delivery and tracking of vaccines. This thesis investigates further development of these technologies toward clinical translation. In the first part, we investigate a locally injectable microparticle system with a core-shell microstructure made from a novel 3D printing process compatible with biodegradable polymers. These microparticles can be used for delayed, pulsatile release of vaccines, therefore reducing the number of administrations to a single one. We study two translational aspects of core-shell microparticles, namely, injectability, and mechanism of pulsatile release. To study injectability, we use a wide range of tools, namely, multiphysics simulation, experiments, machine learning, and 3D printing to establish a framework for optimal injection of microparticle-based drugs. To study the mechanism of pulsatile release, we integrate various experimental tools with multiphysics simulations to form a model describing the mechanism of degradation and pulsatile release from core-shell particles. In the next phase of this thesis we move forward to a transdermal dissolvable microneedle patch without the need for injections. These microneedle patches can be used to track medical record on patient without the need for expensive healthcare infrastructure--a challenge in developing world. Using extensive computational modeling, we establish a design framework for microneedle devices, widely applicable to any microneedle system. Best trade-off design is then selected for administrations in vivo. We further develop a machine learning algorithm coupled with image processing tools to provide long-term pattern classification capability for encoding information transferred by microneedles to the patient, in an automated and robust fashion. Results of this thesis could be of great interest to development of next generation biomedical devices for controlled vaccine delivery and other applications.”

PEG-PLGA and Mal-PEG-PLGA from PolySciTech used in research on Lupus.

Wednesday, June 29, 2022, 1:59 PM ET

Systemic lupus erythematosus (SLE) is the most common type of lupus. SLE is an autoimmune disease in which the immune system attacks its own tissues. Recently, researchers at Harvard University and Mitobridge, Inc. used mPEG-PLGA (5K-30K, cat# AK102) and PLGA-PEG-Mal (5K-30K, cat# AI110) from PolySciTech (www.polyscitech.com) to develop nanoparticles as part of investigating the pathogenicity of lupus. This research holds promise to provide further treatments for lupus. Read More: Chen, P.M., Katsuyama, E., Satyam, A., Li, H., Rubio, J., Jung, S., Andrzejewski, S., Becherer, J.D., Tsokos, M.G., Abdi, R. and Tsokos, G.C., 2022. CD38 reduces mitochondrial fitness and cytotoxic T cell response against viral infection in lupus patients by suppressing mitophagy. Science Advances, 8(24), p.eabo4271. https://www.science.org/doi/abs/10.1126/sciadv.abo4271

“Abstract: Infection is one of the major causes of mortality in patients with systemic lupus erythematosus (SLE). We previously found that CD38, an ectoenzyme that regulates the production of NAD+, is up-regulated in CD8+ T cells of SLE patients and correlates with the risk of infection. Here, we report that CD38 reduces CD8+ T cell function by negatively affecting mitochondrial fitness through the inhibition of multiple steps of mitophagy, a process that is critical for mitochondria quality control. Using a murine lupus model, we found that administration of a CD38 inhibitor in a CD8+ T cell–targeted manner reinvigorated their effector function, reversed the defects in autophagy and mitochondria, and improved viral clearance. We conclude that CD38 represents a target to mitigate infection rates in people with SLE.”

PLGA-PEG from Akina used in research on tumor-mimicking hydrogels for in-vitro testing applications.

Wednesday, June 29, 2022, 1:44 PM ET

In order to develop anticancer medications assays must be developed which enable accurate determination of the efficacy of prototype medicines. Because cancer is a complex 3D structure within the human body these assays need to include the nuances present in the microenvironment. Recently, researchers at University of Queensland (Australia) used PEG-PLGA (Cat# AK026) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to create nanoparticles and use these as part of testing hydrogel-based mimics of tumors for in-vitro development. This research holds promise to improve cancer drug development processes in the future. Read more: Cameron, Anna P., Bijun Zeng, Yun Liu, Haofei Wang, Farhad Soheilmoghaddam, Justin Cooper-White, and Chun-Xia Zhao. "Biophysical properties of hydrogels for mimicking tumor extracellular matrix." Biomaterials Advances 136 (2022): 212782. https://www.sciencedirect.com/science/article/pii/S2772950822000590

“Highlights: Evaluation of biophysical attributes of Matrigel, collagen gel and agarose gel. Characterization of complex modulus, loss tangent, permeability and pore size of hydrogels. A new and facile method for the characterization of hydrogel microstructures. A microfluidic approach for measuring hydrogel permeability. Abstract: The extracellular matrix (ECM) is an essential component of the tumor microenvironment. It plays a critical role in regulating cell-cell and cell-matrix interactions. However, there is lack of systematic and comparative studies on different widely-used ECM mimicking hydrogels and their properties, making the selection of suitable hydrogels for mimicking different in vivo conditions quite random. This study systematically evaluates the biophysical attributes of three widely used natural hydrogels (Matrigel, collagen gel and agarose gel) including complex modulus, loss tangent, diffusive permeability and pore size. A new and facile method was developed combining Critical Point Drying, Scanning Electron Microscopy imaging and a MATLAB image processing program (CSM method) for the characterization of hydrogel microstructures. This CSM method allows accurate measurement of the hydrogel pore size down to nanometer resolution. Furthermore, a microfluidic device was implemented to measure the hydrogel permeability (Pd) as a function of particle size and gel concentration. Among the three gels, collagen gel has the lowest complex modulus, medium pore size, and the highest loss tangent. Agarose gel exhibits the highest complex modulus, the lowest loss tangent and the smallest pore size. Collagen gel and Matrigel produced complex moduli close to that estimated for cancer ECM. The Pd of these hydrogels decreases significantly with the increase of particle size. By assessing different hydrogels' biophysical characteristics, this study provides valuable insights for tailoring their properties for various three-dimensional cancer models.”

Aquagel from PolySciTech used in development of inflatable underwater Naval sonar sensors

Wednesday, June 29, 2022, 1:43 PM ET

Compressive sensors enable sonar detection underwater with less hardware complexity. This allows for cheap, easily deployable, efficient, sonar detection systems that can be used for a wide array of applications. Recently, researchers at the Office of Naval Research Science & Technology utilized Aquagel from Akina, Inc. (https://akinainc.com/polyscitech/products/aquagel/index.php) to develop underwater deployable sonar sensing arrays. This research holds promise to improve detection capabilities for both civillian and military applications. Read more: Ouyang, Bing. Robust Co-Prime Sensing with Underwater Inflatable Passive Sonar Arrays. FLORIDA ATLANTIC UNIV FORT PIERCE FL, 2022. https://apps.dtic.mil/sti/pdfs/AD1169163.pdf

“ABSTRACT: This final technical report describes the effort from May 2018 to September 2021 to accomplish the project objective of Robust Co-Prime Sensing with Underwater Inflatable Passive Sonar Arrays. In many scientific and defense surveillance missions, reducing the sensing systems’ size, weight, and power (SWaP) is critical to accomplishing the intended objectives [1]. The long-term goal of this research is to develop energy-efficient and low-cost underwater inflatable structures that will be the building blocks in many naval applications. While compressive sensing (CS) has been adopted at the backend to maintain signal fidelity with fewer data and reduce the sensing hardware’s complexity, SWaP reduction can also be achieved with intelligent mechanical design. The inflatable structure is adopted for the mechanical design of this sonar array. The inflatable structure, also called the deployable structure, is a folded package with compact stowed dimensions. It can be detached from a carrying platform and morphs into its final form at the destination. On the algorithm side, the concept of the co-prime array is adopted. A co-prime array employs two interleaved uniform linear subarrays with several co-prime elements and inter-element spacing. It can resolve a much higher number of sources than a conventional uniform half-wavelength spaced array for a given number of sensors. Therefore, integrating these two concepts, i.e., “two-way compression,” reduces both the structural dimension of a sonar array and the number of hydrophones in the array. During the three-year funding period, the team investigated alternatives to the conventional Mechanical Based Expansion (MBE), including Physics-Based Expansion (PBE) and Chemical Based Expansion (CBE). The feasibility of these techniques, particularly the PBE approach, has been validated through numerical modeling, lab test, and field study. Our study has produced two pending patents, and one journal paper (in press). The results have also been presented at multiple technical conferences.”

PLGA-PEG-amine from PolySciTech used in development of Photodynamic therapy delivery system for targeted treatment of cancer

Wednesday, June 15, 2022, 2:07 PM ET

Photodynamic therapy is a process by which a delivery system is combined with external illumination as a means to specifically target and affect tumor cells. A specific challenge for this system is delivery of the appropriate photosensitizer molecule to the site of action. Recently, researchers at University of Madrid and Harvard Medical School used PLGA-PEG-NH2 (cat# AI058) from the PolySciTech (www.polyscitech.com) division of Akina, Inc to develop a delivery system. They reacted this with hyaluronic acid to create a unique nanoparticle for carrying of Ruthenium complexes. This research hold promise to improve therapy options against cancer in the future. Read more: Quilez Alburquerque, jose and Saad, Mohammad Ahsan and Descalzo, Ana B. and Orellana, Guillermo and Hasan, Tayyaba, Hyaluronic Acid-Poly(Lactic-Co-Glycolic Acid) Nanoparticles with a Ruthenium Photosensitizer Cargo for Photokilling of Oral Cancer Cells. Available at SSRN: https://ssrn.com/abstract=4131246or http://dx.doi.org/10.2139/ssrn.4131246

“Photodynamic therapy (PDT), a combination of light, molecular oxygen and a photosensitizing dye, has gained attention as a promising technique to treat various types of cancers. Among all the photosensitizers reported so far, ruthenium(II) polypyridyl complexes exhibit unique photophysical and photobiological features owing to their photostability, ms triplet excited states, and ability to undergo both ‘type I’ and ‘type II’ reactions in their photodynamic action. We report the synthesis a novel Ru(II) complex containing one 2,2'-biimidazole (bim) and two tetramethylphenanthroline (tmp) ligands that sensitizes the simultaneous production of superoxide anion (O 2 · - ) and singlet oxygen ( 1 O 2 ) upon irradiation with blue-green light. To improve its solubility and bioavailability, a zero-order degradation-controlled release formulation based on self-assembled hyaluronic acid (HA)–poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) was prepared for its topical application in oral cancer cells (TR146 cell line). These NPs (152 nm diameter) showed 70% Ru-complex encapsulation efficiency, high physiological stability, low polydispersity index (0.12), and a sensitizer release enhanced by the hyaluronidase enzyme overexpressed in many cancer cells. Both the free complex and its nanocarrier are internalized by the TR146 cells, displaying >90% in vitro cytotoxicity under 470 nm activation (50 J cm⁻ 2 ), highlighting their potential as PDT agents. As hypoxia associated with oral and other cancers is a major barrier to photodynamic therapy which is being clinically employed for oral cancer management, the Ru(II) complex loaded nanocarrier developed in this study can be effective in the treatment of early stage oral cancers and disinfection of wounds where light penetration is not a pre-requisite. Keywords: Photodynamic therapy, Ru(II) complex, hyaluronic acid-poly(lactic-co-glycolic acid), superoxide anion”

PLGA-PEG-PLGA from PolySciTech used in delivery of Ponatinib for cancer therapy

Monday, June 6, 2022, 1:28 PM ET

Tyrosine kinase inhibitors (TKIs) are a new generation of anti-cancer drugs which can prevent cancer growth and spread however these do display cardiotoxicity. Encapsulating the TKI can prevent toxic effects towards heart tissue. Recently, researchers at Qatar University and Ss. Cyril and Methodius University in Skopje used PLGA-PEG-PLGA (cat# AK032) from PolySciTech (www.polyscitech.com) to make nanoparticles loaded with Ponatinib and these were used for measurement of toxicty and efficacy in a zebrafish model. This research holds promise to improve therapies against cancer in the future. Read more: Al-Thani, Hissa F., Samar Shurbaji, Zain Zaki Zakaria, Maram H. Hasan, Katerina Goracinova, Hesham M. Korashy, and Huseyin C. Yalcin. "Reduced Cardiotoxicity of Ponatinib-Loaded PLGA-PEG-PLGA Nanoparticles in Zebrafish Xenograft Model." Materials 15, no. 11 (2022): 3960. https://www.mdpi.com/1996-1944/15/11/3960

“Abstract: Tyrosine kinase inhibitors (TKIs) are the new generation of anti-cancer drugs with high potential against cancer cells’ proliferation and growth. However, TKIs are associated with severe cardiotoxicity, limiting their clinical value. One TKI that has been developed recently but not explored much is Ponatinib. The use of nanoparticles (NPs) as a better therapeutic agent to deliver anti-cancer drugs and reduce their cardiotoxicity has been recently considered. In this study, with the aim to reduce Ponatinib cardiotoxicity, Poly(D,L-lactide-co-glycolide)-b-poly(ethyleneoxide)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer was used to synthesize Ponatinib in loaded PLGA-PEG-PLGA NPs for chronic myeloid leukemia (CML) treatment. In addition to physicochemical NPs characterization (NPs shape, size, size distribution, surface charge, dissolution rate, drug content, and efficacy of encapsulation) the efficacy and safety of these drug-delivery systems were assessed in vivo using zebrafish. Zebrafish are a powerful animal model for investigating the cardiotoxicity associated with anti-cancer drugs such as TKIs, to determine the optimum concentration of smart NPs with the least side effects, and to generate a xenograft model of several cancer types. Therefore, the cardiotoxicity of unloaded and drug-loaded PLGA-PEG-PLGA NPs was studied using the zebrafish model by measuring the survival rate and cardiac function parameters, and therapeutic concentration for in vivo efficacy studies was optimized in an in vivo setting. Further, the efficacy of drug-loaded PLGA-PEG-PLGA NPs was tested on the zebrafish cancer xenograft model, in which human myelogenous leukemia cell line K562 was transplanted into zebrafish embryos. Our results demonstrated that the Ponatinib-loaded PLGA-PEG-PLGA NPs at a concentration of 0.001 mg/mL are non-toxic/non-cardio-toxic in the studied zebrafish xenograft model. Keywords: zebrafish; leukemia; nanomedicine; nanoparticle; pre-clinical; cardiotoxicity; cancer; Ponatinib; xenograft; PLGA”

PLLA-Fluorescein from PolySciTech used in development of contraceptive microneedle

Thursday, May 26, 2022, 1:58 PM ET

One method for drug-delivery is to utilize microneedles, patches comprised of very small biodegradable needles too small to see. These can be used for long-lasting delivery of agents including contraceptives. Recently, researchers at Georgia Institute of Technology, University of Michigan, and Wuhan University (China) used PLLA-Fluorescein (AV004) from PolySciTech (www.polyscitech.com) to create fluorescently strained microparticles for delivery of contraceptive hormone, levonorgestrel. This research holds promise to provide for extended contraceptive action in a less invasive manner than existing products such as IUDs. Read more: Li, Wei, Jonathan Yuxuan Chen, Richard N. Terry, Jie Tang, Andrey Romanyuk, Steven P. Schwendeman, and Mark R. Prausnitz. "Core-shell microneedle patch for six-month controlled-release contraceptive delivery." Journal of Controlled Release 347 (2022): 489-499. https://www.sciencedirect.com/science/article/pii/S0168365922002656

“Highlights: Developed a novel core-shell microneedle where the shell is a rate-controlling membrane to achieve zero-order drug release. Constructed the core-shell structure by sequential casting into a single mold by solvent engineering. Achieved six-month controlled-release contraceptive delivery in vitro. Abstract: There is a tremendous need for simple-to-administer, long-acting contraception, which can increase access to improved family planning. Microneedle (MN) patches enable simple self-administration and have previously been formulated for 1–2 months-controlled release of contraceptive hormone using monolithic polymer/drug MN designs having first-order release kinetics. To achieve zero-order release, we developed a novel core-shell MN patch where the shell acts as a rate-controlling membrane to delay release of a contraceptive hormone, levonorgestrel (LNG), for 6 months. In this approach, LNG was encapsulated in a poly(lactide-co-glycolide) (PLGA) core surrounded by a poly(l-lactide) (PLLA) shell and a poly(D,L-lactide) (PLA) cap that were fabricated by sequential casting into a MN mold. Upon application to skin, the core-shell MNs utilized an effervescent interface to separate from the patch backing within 1 min. The core-shell design limited the initial 24 h burst release of LNG to 5.8 ± 0.5% and achieved roughly zero-order LNG release for 6.2 ± 0.1 months in vitro. A monolithic MN patch formulated with the same LNG and PLGA core, but without the rate-controlling PLLA shell and PLA cap had a larger LNG burst release of 22.6 ± 2.0% and achieved LNG release for just 2.1 ± 0.2 months. This study provides the first core-shell MN patch for controlled months-long drug release and supports the development of long-acting contraception using a simple-to-administer, twice-per-year MN patch.”

PLCL from PolySciTech used in development of sprayable tissue adhesive for surgical applications

Wednesday, May 18, 2022, 3:51 PM ET

After surgery it is not uncommon for various internal tissues to heal together inappropriately, i.e. certain layers of tissue will heal to one another rather than as discrete layers. This problem can lead to adhesions, fibrous bridges that connect tissue surfaces together and is usually affiliated with an inflammatory response post-surgery. These adhesions can lead to severe pain as well as bowel obstruction and infertility, depending on their location. Recently, researchers at University of Maryland, Massachusetts Institute of Technology, and Children’s National Medical Center utilized various PLCL polymers (cat# AP212, AP178, AP179, and AP151) from PolySciTech (www.polyscitech.com) to create a spray-on layer of biodegradable polymer that reduces the formation of these adhesions between tissues. This research holds promise to reduce this common post-surgical complication. Read more: Erdi, Metecan, Selim Rozyyev, Manogna Balabhadrapatruni, Michele S. Saruwatari, John L. Daristotle, Omar B. Ayyub, Anthony D. Sandler, and Peter Kofinas. "Sprayable Tissue Adhesive with Biodegradation Tuned for Prevention of Post‐Operative Abdominal Adhesions." Bioengineering & Translational Medicine: e10335. https://aiche.onlinelibrary.wiley.com/doi/abs/10.1002/btm2.10335

“Abstract: Adhesions are dense, fibrous bridges that adjoin tissue surfaces due to uncontrolled inflammation following post-operative mesothelial injury. A widely used adhesion barrier material in Seprafilm often fails to prevent transverse scar tissue deposition because of its poor mechanical properties, rapid degradation profile, and difficulty in precise application. Solution blow spinning (SBS), a polymer fiber deposition technique, allows for the placement of in-situ tissue-conforming and tissue-adherent scaffolds with exceptional mechanical properties. While biodegradable polymers such as poly(lactic-co-glycolic acid) (PLGA) have desirable strength, they exhibit bulk biodegradation rates and inflammatory profiles that limit their use as adhesion barriers and result in poor tissue adhesion. Here, viscoelastic poly(lactide-co-caprolactone) (PLCL) is used for its pertinent biodegradation mechanism. Because it degrades via surface erosion, spray deposited PLCL fibers can dissolve new connections formed by inflamed tissue, allowing them to function as an effective, durable, and easy to apply adhesion barrier. Degradation kinetics are tuned to match adhesion formation through design of PLCL blends comprised of highly adhesive “low” molecular weight (LMW) constituents in a mechanically robust “high” molecular weight (HMW) matrix. In-vitro studies demonstrate that blending LMW PLCL (30% w/v) with HMW PLCL (70% w/v) yields an anti-fibrotic yet tissue-adhesive polymer sealant with a 14-day erosion rate countering adhesion formation. PLCL blends additionally exhibit improved wet tissue adhesion strength (~10 kPa) over a 14-day period versus previously explored biodegradable polymer compositions, such as PLGA. In a mouse cecal ligation model, select PLCL blends significantly reduce abdominal adhesions severity versus no treatment and Seprafilm treated controls.”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.3874351978302 seconds)


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