John Garner's Technical Blog
John GarnerJohn Garner, Manager

What's New and on the Manager's Mind

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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PLGA from PolySciTech used in development of antibiotic releasing surgical clip

Friday, January 15, 2021, 8:50 AM ET

Whenever an incision is made in a patient as part of surgery there is a potential for infection to spread as bacteria grow in the wound. Typical surgical-practice measures (sterilization of instruments, scrubbing-in, wearing of surgical masks, etc.) minimize the potential for bacteria to invade the space, however post-surgical infections still occur as it is nearly impossible to completely eliminate all bacteria from a given area. Recently, researchers at Drexel University and Exponent Inc. used PLGA (AP075) from PolySciTech (www.polyscitech.com) to create a surgical clip that releases vancomycin (antibiotic) to prevent post-surgical infections. This research holds promise to improve surgical outcomes. Read more: Schachtner, J., R. Nathan, M. Rajaghatta, B. Shah, A. Suarez, N. Hickok, and S. Kurtz. "3D-Printed Bioresorbable Antibiotic Spacer Clip for the Prevention of Spinal Surgical Site Infection." Antimicrobial Combination Devices: 65-74. https://www.astm.org/DIGITAL_LIBRARY/STP/PAGES/STP163020190143.htm

“Abstract: Surgical site infections (SSIs) are serious complications of spinal fusion surgery and are often difficult to eradicate due to the formation of bacterial biofilms on the implanted hardware. SSIs affect 1% to 8.5% of patients after spinal surgery, with a 2.1% SSI rate after lumbar spinal fusion surgery. The objective of this study is to aid in the prevention of spinal SSIs by designing an adjunct to spinal hardware that contains a reservoir for the bolus release and extended release of prophylactic antibiotics in order to reduce the consequences of these painful, costly, and life-threatening infections. A clip was designed with a dual wall that includes an inner structural layer of polylactic acid (PLA) to contain vancomycin and an outer composite layer of poly(lactic-co-glycolic acid) (PLGA) and vancomycin. The inner well is ruptured by ultrasound to allow the bolus vancomycin release. An extended release of vancomycin then continues as the material of the clip degrades. The clip was printed using a dual-head three-dimensional (3D) printer to enable two separate types of filament—a coextruded PLGA/vancomycin composite for the outer wall and a medical-grade PLA for structural support. The PLGA/vancomycin material was evaluated for its efficacy against Staphylococcus aureus and its ability to prevent biofilm formation. This material was tested against three control groups, and the processed antibiotic was shown to be as effective as the unprocessed vancomycin solution. To understand the extended-release profile of the material, tests were conducted to study the zones of inhibition of the antibiotic eluted from the clip in PBS over a period of 10 days. This study presents an opportunity for the development of antimicrobial devices in 3D printing and the possibility of different antibiotic and polymer composite materials. Keywords: 3D printing, fused filament fabrication, bioresorbable polymer, surgical site infection, PLGA, Staphylococcus aureus, vancomycin, antimicrobial”

PEG-PLA from PolySciTech used to investigate the impact of chemotherapy delivery during pregnancy

Thursday, January 14, 2021, 9:02 AM ET

Treatment of breast cancer during pregnancy can be problematic as care must be taken to ensure the therapy applied doesn’t damage either mother or child. Unfortunately, many of the conventional chemotherapeutic agents used to prevent the growth of cancer can also negatively impact the growing fetus. Recently, researchers at University of Texas used mPEG-PLA (AK069) from PolySciTech (www.polyscitech.com) to investigate the effects of nanoparticle formulations on placental uptake in pregnant women. This research highlights the need for diligence and care with treating breast cancer in pregnant women without causing damage to other areas. Read more: Ali, Shariq, Norah A. Albekairi, Sanaalarab Al-Enazy, Mansi Shah, Svetlana Patrikeeva, Tatiana N. Nanovskaya, Mahmoud S. Ahmed, and Erik Rytting. "Formulation effects on paclitaxel transfer and uptake in the human placenta." Nanomedicine: Nanotechnology, Biology and Medicine: 102354. https://www.sciencedirect.com/science/article/pii/S1549963420302082

“Highlights: Nanoparticle formulations of drugs alter their permeability across human placenta. Encapsulation of paclitaxel in micelles prevents placental efflux by P-glycoprotein. Reduced efflux of paclitaxel leads to increased placental accumulation. Abstract: Diagnosis and treatment of breast cancer in pregnancy can result in morbidity and mortality for the mother and fetus. Many new paclitaxel nanoformulations commercially available worldwide for breast cancer treatment are being adopted due to favorable dosing regimens and side effect profiles, but their transplacental transport and resultant fetal exposure remains unknown. Here, we examine three formulations: Taxol (paclitaxel dissolved in Kolliphor EL and ethanol); Abraxane (albumin nanoparticle); and Genexol-PM (polymeric micelle). In the ex vivo dually perfused human placental cotyledon, placental accumulation of Genexol-PM is higher than Taxol, and both nanoformulations have lower maternal concentrations of paclitaxel over time. In vitro studies of these formulations and fluorescent nanoparticle analogs demonstrate that Genexol-PM allows paclitaxel to overcome P-glycoprotein efflux, but Abraxane behaves as a free drug formulation. We anticipate that these findings will impact future development of rational and safe treatment strategies for pregnancy-associated breast cancer and other diseases.”

PLGA from PolySciTech used in development of Gel-Microparticle Erlotinib delivery system for cancer therapy

Thursday, January 14, 2021, 9:01 AM ET

Many therapeutic agents which are effective against cancer also have negative side effects in other parts of the body which leads to a need for a localized delivery system. Recently, researchers at University of California Los Angeles and Kangwon National University (Korea) used PLGA (AP045) from PolySciTech (www.polyscitech.com) to make ERT loaded microparticles for testing their cancer treatment potentials in a gel system. This research holds promise for improved cancer therapies. Read more: Lee, Song Yi, Mingyu Yang, Ji-Hye Seo, Da In Jeong, ChaeRim Hwang, Han-Jun Kim, Junmin Lee, KangJu Lee, JiHye Park, and Hyun-Jong Cho. "Serially pH-Modulated Hydrogels Based on Boronate Ester and Polydopamine Linkages for Local Cancer Therapy." ACS Applied Materials & Interfaces. https://pubs.acs.org/doi/abs/10.1021/acsami.0c16199

“Elaborately and serially pH-modulated hydrogels possessing optimized viscoelastic natures for short gelation time and single syringe injection were designed for peritumoral injection of an anticancer agent. Boronate ester bonds between phenylboronic acid (PBA) (installed in HA-PBA (HP)) and dopamine (included in HA-dopamine (HD)) along with self-polymerization of dopamine (via interactions between HD conjugates) were introduced as the main cross-linking strategies of a hyaluronic acid (HA) hydrogel. Considering pKa values (8.0–9.5) of PBA and dopamine, the pH of each polymer dispersion was controlled elaborately for injection through a single syringe, and the final pH was tuned nearby the physiological pH (pH 7.8). The shear-thinning behavior, self-healing property, and single syringe injectability of a designed hydrogel cross-linked nearby physiological pH may provide its convenient application to peritumoral injection and prolonged retention in local cancer therapy. Erlotinib (ERT) was encapsulated in a microsphere (MS), and it was further embedded in an HP/HD-based hydrogel for sustained and locoregional delivery. A rheologically tuned hydrogel containing an ERT MS exhibited superior tumor-suppressive efficiencies compared to the other groups in A549 tumor-bearing mice. A designed injectable hydrogel through a single syringe system may be efficiently applied to local cancer therapy with lower toxicities to healthy organs.”

PEG-PLGA from PolySciTech used in development of Parkinson’s disease therapy

Thursday, January 14, 2021, 9:00 AM ET

Parkinson’s disease affects the nervous system and leads to decreased motor control. A treatment for this disease is Levodopa however this drug has cardiovascular side effects which makes targeted delivery preferable to system. Recently, researchers at Sun Yat-sen University (China), Ocean University of China, and Johns Hopkins University, Used mPEG-PLGA (AK101) from PolySciTech (www.polyscitech.com) to investigate nanoparticle formulations for treatment of Parkinson’s disease by delivery of levodopa. This research holds promise to improve therapies against Parkinson’s disease. Read more: Nie, Tianqi, Zhiyu He, Jinchang Zhu, Kuntao Chen, Gregory P. Howard, Jesus Pacheco-Torres, Il Minn et al. "Non-invasive delivery of levodopa-loaded nanoparticles to the brain via lymphatic vasculature to enhance treatment of Parkinson’s disease." Nano Research: 1-13. https://link.springer.com/article/10.1007/s12274-020-3280-0

“Abstract: Levodopa (L-DOPA), a precursor of dopamine, is commonly prescribed for the treatment of the Parkinson’s disease (PD). However, oral administration of levodopa results in a high level of homocysteine in the peripheral circulation, thereby elevating the risk of cardiovascular disease, and limiting its clinical application. Here, we report a non-invasive method to deliver levodopa to the brain by delivering L-DOPA-loaded sub-50 nm nanoparticles via brain-lymphatic vasculature. The hydrophilic L-DOPA was successfully encapsulated into nanoparticles of tannic acid (TA)/polyvinyl alcohol (PVA) via hydrogen bonding using the flash nanocomplexation (FNC) process, resulting in a high L-DOPA-loading capacity and uniform size in a scalable manner. Pharmacodynamics analysis in a PD rat model demonstrated that the levels of dopamine and tyrosine hydroxylase, which indicate the dopaminergic neuron functions, were increased by 2- and 4-fold, respectively. Movement disorders and cerebral oxidative stress of the rats were significantly improved. This formulation exhibited a high degree of biocompatibility as evidenced by lack of induced inflammation or other pathological changes in major organs. This antioxidative and drug-delivery platform administered through the brain-lymphatic vasculature shows promise for clinical treatment of the PD.”

PLGA from PolySciTech used for development of PEG-protected nanoparticles for enzyme delivery

Tuesday, January 12, 2021, 2:06 PM ET

The process of making nanoparticles is fundamentally rooted in precipitation of the polymer in aqeous phase to form the solid. There are a multitude of variables around how this is performed and which components (PLGA, PLGA-PEG, solvents, emulsifying agents) are used. Recently, researchers from University of Washington used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create nanoparticles and study the processing sonication and other parameters on their resultant toxicity and enzyme carrying capabilities. This holds promise to gain futher understanding about the use of nanoparticles as enzymatic carriers. Read more: Liao, Rick, Jessica Pon, Michael Chungyoun, and Elizabeth Nance. "Enzymatic protection and biocompatibility screening of enzyme-loaded polymeric nanoparticles for neurotherapeutic applications." Biomaterials 257 (2020): 120238. https://www.sciencedirect.com/science/article/pii/S0142961220304841

“Abstract: Polymeric nanoparticles provide a non-invasive strategy for enhancing the delivery of labile hydrophilic enzymatic cargo for neurological disease applications. One of the most common polymeric materials, poly(lactic-co-glycolic acid) (PLGA) copolymerized with poly(ethylene glycol) (PEG) is widely studied due to its biocompatible and biodegradable nature. Although PLGA-PEG nanoparticles are generally known to be non-toxic and protect enzymatic cargo from degradative proteases, different formulation parameters including surfactant, organic solvent, sonication times, and formulation method can all impact the final nanoparticle characteristics. We show that 30s sonication double emulsion (DE)-formulated nanoparticles achieved the highest enzymatic activity and provided the greatest enzymatic activity protection in degradative conditions, while nanoprecipitation (NPPT)-formulated nanoparticles exhibited no protection compared to free catalase. However, the same DE nanoparticles also caused significant toxicity on excitotoxicity-induced brain tissue slices, but not on healthy or neuroinflammation-induced tissue. We narrowed the culprit of toxicity to specifically sonication of PLGA-PEG polymer with dichloromethane (DCM) as the organic solvent, independent of surfactant type. We also discovered that toxicity was oxidative stress-dependent, but that increased toxicity was not enacted through increasing oxidative stress. Furthermore, no PEG degradation or aldehyde, alcohol, or carboxylic acid functional groups were detected after sonication. We identified that inclusion of free PEG along with PLGA-PEG polymer during the emulsification phases or replacing DCM with trichloromethane (chloroform) produced biocompatible polymeric nanoparticle formulations that still provided enzymatic protection. This work encourages thorough screening of nanoparticle toxicity and cargo-protective capabilities for the development of enzyme-loaded polymeric nanoparticles for the treatment of disease.”

PLGA from PolySciTech used in development of localized microparticle arthritis treatment

Tuesday, January 12, 2021, 2:05 PM ET

Arthritis is a disease in which the cartilage of joints is damaged by immune response as well as trauma and age which leads to damage of chondrocytes. Rapamycin has the ability to help chondrocytes heal cartilage but is limited in use due to systemic toxicity. Recently, researchers at Indian Institute of Science used PLGA (AP041) from PolySciTech (www.polyscitech.com) to create microparticles for localized rapamycin delivery to joint tissue. This research holds promise to provide for improved therapies against arthritis. Read more: Dhanabalan, Kaamini M., Vishal K. Gupta, and Rachit Agarwal. "Rapamycin–PLGA microparticles prevent senescence, sustain cartilage matrix production under stress and exhibit prolonged retention in mouse joints." Biomaterials science 8, no. 15 (2020): 4308-4321. https://pubs.rsc.org/no/content/articlehtml/2020/bm/d0bm00596g

“Osteoarthritis (OA) is a joint disease characterized by progressive damage of articular cartilage and the adjoining subchondral bone. Chondrocytes, the primary cells of the cartilage, have limited regenerative capacity and when they undergo stress due to trauma or with aging, they senesce or become apoptotic. Rapamycin, a potent immunomodulator, has shown promise in OA treatment. It activates autophagy and is known to prevent senescence. However, its clinical translation for OA is hampered due to systemic toxicity as high and frequent doses are required. Here, we have fabricated rapamycin encapsulated poly(lactic-co-glycolic acid) (PLGA) based carriers that induced autophagy and prevented cellular senescence in human chondrocytes. The microparticle (MP) delivery system showed sustained release of the drug for several weeks. Rapamycin microparticles protected in vitro cartilage mimics (micromass cultures) from degradation, allowing sustained production of sGAG, and demonstrated a prolonged senescence preventive effect under oxidative and genomic stress conditions. These microparticles also exhibited a residence time of ∼30 days after intra-articular injections in murine knee joints. Such particulate systems are promising candidates for intra-articular delivery of rapamycin for the treatment of osteoarthritis.”

PLGA from PolySciTech used in development of novel microfabrication technique for generating drug-loaded microparticles

Wednesday, January 6, 2021, 9:43 AM ET

Most general engineering is accomplished by macroscopic manufacturing techniques of conventional cutting, molding, milling, and other shaping applications. These methods generally do not work at the submicron scale which is smaller than what conventional machinery can handle. Recently, researchers at the Technical University of Denmark utilized PLGA (AP036) from PolySciTech (www.polyscitech.com) to create a sheet of Furosemide (an anti-edema drug used to reduce swelling) loaded PLGA and then cut out a series of microparticles from it using a novel Micromechanical Punching technique. This research holds promise to provide for improved manufacturing techniques to generate microparticles. Read more: Petersen, Ritika Singh, Anja Boisen, and Stephan Sylvest Keller. "Micromechanical Punching: A Versatile Method for Non-Spherical Microparticle Fabrication." Polymers 13, no. 1 (2021): 83. https://www.mdpi.com/2073-4360/13/1/83

“Abstract: Microparticles are ubiquitous in applications ranging from electronics and drug delivery to cosmetics and food. Conventionally, non-spherical microparticles in various materials with specific shapes, sizes, and physicochemical properties have been fabricated using cleanroom-free lithography techniques such as soft lithography and its high-resolution version particle replication in non-wetting template (PRINT). These methods process the particle material in its liquid/semi-liquid state by deformable molds, limiting the materials from which the particles and the molds can be fabricated. In this study, the microparticle material is exploited as a sheet placed on a deformable substrate, punched by a robust mold. Drawing inspiration from the macro-manufacturing technique of punching metallic sheets, Micromechanical Punching (MMP) is a high-throughput technique for fabrication of non-spherical microparticles. MMP allows production of microparticles from prepatterned, porous, and fibrous films, constituting thermoplastics and thermosetting polymers. As an illustration of application of MMP in drug delivery, flat, microdisk-shaped Furosemide embedded poly(lactic-co-glycolic acid) microparticles are fabricated and Furosemide release is observed. Thus, it is shown in the paper that Micromechanical punching has potential to make micro/nanofabrication more accessible to the research and industrial communities active in applications that require engineered particles. Keywords: non-spherical microparticle; soft lithography; drug delivery; punching”

mPEG-PCL from PolySciTech used in development of docetaxel/osthol dual-drug delivery system for treatment of cancer

Tuesday, January 5, 2021, 11:45 AM ET

The treatment of cancer requires delivery of medicinal compounds to the site of cancer itself. However, often, the drugs used for cancer therapy have very poor water solubility and bad bioavailability (poor absorption). One means to rectify this is to utilize block copolymers to form micelles with interior hydrophobic portions (often degradable polyesters such as PLA, PCL, or PLGA) surrounded by hydrophilic exterior (often polyethylene glycol). In this case the hydrophobic drugs can be loaded into the oil-soluble interior and the micelle as a whole can circulate more freely in the bloodstream for improved uptake. Recently, Researchers at Chungbuk National University and Sookmyung Women’s University (Korea) used mPEG-PCL (AK073) from PolySciTech (www.polyscitech.com) to create micelles loaded with docetaxel and osthol for cancer therapy uses. This research holds promise to provide for improved cancer therapies in the future. Read More: Jo, Min Jeong, Yu Jin Lee, Chun-Woong Park, Youn Bok Chung, Jin-Seok Kim, Mi Kyeong Lee, and Dae Hwan Shin. "Evaluation of the Physicochemical Properties, Pharmacokinetics, and In Vitro Anticancer Effects of Docetaxel and Osthol Encapsulated in Methoxy Poly (ethylene glycol)-b-Poly (caprolactone) Polymeric Micelles." International Journal of Molecular Sciences 22, no. 1 (2021): 231. https://www.mdpi.com/1422-0067/22/1/231

“Docetaxel (DTX), a taxane-based anticancer drug, and osthol (OTH), a coumarin-derivative compound, have shown anticancer effects against different types of cancers through various mechanisms. However, these drugs have low solubility in water and low oral bioavailability, and thus their clinical application is difficult. To overcome these problems, we encapsulated DTX and OTH in methoxy poly(ethylene glycol)-b-poly(caprolactone) (mPEG-b-PCL) and conducted studies in vitro and in vivo. We selected a 1:4 ratio as the optimal ratio of DTX and OTH, through combination index analysis in A549 cancer cells, and prepared micelles to evaluate the encapsulation efficiency, drug loading, particle size, and zeta potential. The in vitro drug-release profile showed that DTX/OTH-loaded mPEG-b-PCL micelles could slowly release DTX and OTH. In the clonogenic assay, DTX/OTH-loaded mPEG-b-PCL micelles showed 3.7 times higher inhibitory effect than the DTX/OTH solution. Pharmacokinetic studies demonstrated that micelles in combination with DTX and OTH exhibited increased area under curve and decreased clearance values, as compared with single micelles. Keywords: docetaxel; osthol; mPEG-b-PCL polymeric micelles; combination therapy; pharmacokinetics”

PLGA-PEG-PLGA and PLCL-PEG-PLCL from PolySciTech used in development of Thermogel-based drug-delivery platform

Monday, January 4, 2021, 3:24 PM ET

Thermogels are a specific class of polymers which have the unique ability to transition from a liquid into a solid or semi-solid gel upon heating. These can potentially be used for delivery of delicate, large-molecule drugs such as proteins and enzymes. The advantage to this is that the formulations can be generated entirely in water which is an advantage over most other formulations such as microparticles and nanoparticles that require processing in an organic solvent that might damage the protein. Recently, researchers at Amgen, Inc. and Bristol Myers Squibb used PLGA-PEG-PLGA (AK097) and PLCL-PEG-PLCL (AK109) from PolySciTech (www.polyscitech.com) to develop test formulations to deliver the model enzyme lysozyme. This research holds promise to provide for novel protein-based drug delivery systems that could be applied for treating an array of disease conditions. Read more: Agarwal, Prashant, Daniel G. Greene, Scott Sherman, Kaitlyn Wendl, Leonela Vega, Hyunsoo Park, Roman Shimanovich, and Darren L. Reid. "Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies." European Journal of Pharmaceutical Sciences (2020): 105689. https://www.sciencedirect.com/science/article/pii/S0928098720304772

“Highlights: Mesh size, modulus, injectability, viscosity, Tsol-gel are important structural parameters and developability constraints for hydrogels. Mesh size (SAXS/Rheology) of hydrogels > size (RH) of lysozyme suggesting that obstruction by polymer network doesn't hinder diffusion. ∼2x greater amount of lysozyme released from PLCL hydrogel as compared to PLGA, due to the higher viscosity of PLGA, increasing frictional drag on lysozyme and reducing its diffusivity. Tsol-gel (25 - 32°C) and injectability (injection force < 20N) confirmed that these hydrogels can be rapidly implemented during preclinical development. Abstract: Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation. Two commercially available thermosensitive hydrogel systems, comprised of block copolymers of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone)-b-poly(ethyleneglycol)-b-poly(lactide-co-caprolactone) (PLCL), were evaluated during this study. The two block copolymers described in the study were successfully formulated to form hydrogels which delayed the release of lysozyme (> 20 days) in vitro. Characterization of formulation attributes of the hydrogels like Tsol-gel temperature, complex viscosity and injection force showed that these systems are amenable to rapid implementation in preclinical studies. Understanding the structure of the gel network is critical to determine the factors controlling the release of therapeutics out of these gels. The structures were characterized via the gel mesh sizes, which were estimated using two orthogonal techniques: small angle X-ray scattering (SAXS) and rheology. The mesh sizes of these hydrogels were larger than the hydrodynamic radius (size) of lysozyme (drug), indicating that release through these gels is expected to be diffusive at all time scales rather than sub-diffusive. In vitro drug release experiments confirm that diffusion is the dominating mechanism for lysozyme release; with no contribution from degradation, erosion, relaxation, swelling of the polymer network or drug-polymer interactions. PLGA hydrogel was found to have a much higher complex viscosity than PLCL hydrogel, which correlates with the slower diffusivity and release of lysozyme seen from the PLGA hydrogel as compared to PLCL hydrogel. This is due to the increased frictional drag experienced by the lysozyme molecule in the PLGA hydrogel network, as described by the hydrodynamic theory.”

Patents published using PEG-PLA block polymers and PLGA from PolySciTech for drug delivery applications

Tuesday, December 22, 2020, 4:48 PM ET

Much of the research work around PolySciTech products comes out as scientific research articles. However, in addition to these a great deal of research comes out in the form of patents on various developments created using PolySciTech products for an array of biomedical applications. Recently, two patents have been published using PolySciTech products. A recent patent by Phosphorex uses mPEG-PLA (AK031) from PolySciTech (www.polyscitech.com) to create encapsulated particles for drug delivery applications. Wu, Bin, and Paul Boucher. "NOVEL PHARMACEUTICAL FORMULATIONS CONTAINING INDIRUBIN AND DERIVATIVES THEREOF AND METHODS OF MAKING AND USING THE SAME." U.S. Patent Application 16/986,526, filed December 10, 2020. https://www.freepatentsonline.com/y2020/0383931.html “The invention described herein provides various indirubin compositions for treating diseases.” A recent patent by Northwestern University uses PLGA from PolySciTech (www.polyscitech.com) as part of nanoparticle formulation. Read more: Scott, Evan A., Guillermo A. Ameer, Jacqueline A. Burke, Sean D. Allen, and Sijia Yi. "POLY (ETHYLENE GLYCOL)-BLOCK-POLY (PROPYLENE SULFIDE) NANOCARRIER PLATFORM FOR ENHANCED EFFICACY OF IMMUNOSUPPRESSIVE AGENTS." U.S. Patent Application 16/891,391, filed December 10, 2020. https://www.freepatentsonline.com/y2020/0383917.html. “Provided herein are nanocarriers for delivery of immunosuppressive agents. In some embodiments, provided herein are nanocarriers comprising a core comprising a poly(ethylene glycol)-block-poly(propylene sulfide) copolymer and least one therapeutic agent. In some embodiments, the nanocarriers may further comprise a targeting ligand displayed on a surface of the nanocarrier. The at least one therapeutic agent may be an anti-inflammatory agent. The disclosed nanocarriers may be incorporated into pharmaceutical compositions for use in methods of treating an inflammatory condition or preventing transplantation rejection in a subject.”

Fluorescent-Chitosan from PolySciTech used in development of surgical glue for wound healing

Monday, December 21, 2020, 11:01 AM ET

During surgery or after trauma it is necessary to hold the cut pieces of tissue together as well as to control the bleeding. Conventional sutures and staples can be applied to generally close most tissues however there are several situations with either constrained spaces or certain biological features where these do not work well. In this case a biocompatible and biodegradable glue which can bind the tissues together until they can complete healing is preferred. Recently, Researchers at Massachusetts Institute of Technology (MIT) used Fluorescently-bound chitosan (KITO-8) from PolySciTech (www.polyscitech.com) to visualize paste localization and clotting effect. This research holds promise to provide for a useful surgical tool in the future. Read more: Yuk, Hyunwoo, Jingjing Wu, Xinyu Mao, Claudia E. Varela, Ellen T. Roche, Christoph S. Nabzdyk, and Xuanhe Zhao. "Barnacle-Inspired Paste for Instant Hemostatic Tissue Sealing." bioRxiv (2020). https://www.biorxiv.org/content/10.1101/2020.12.12.422505v1.abstract

“Whilst sealing damaged tissues by adhesives has potential advantages over suturing or stapling, existing tissue adhesives cannot form rapid or robust adhesion on tissues covered with body fluids such as blood. In contrast, the glues of barnacles, consisting of a lipid-rich matrix and adhesive proteins, and can strongly adhere to wet and contaminated surfaces. Here we report a barnacle-inspired paste capable of forming instant robust hemostatic sealing of diverse tissues. The paste is composed of a hydrophobic oil matrix and bioadhesive microparticles to implement the barnacle-inspired mechanism to repel blood through the hydrophobic matrix. Subsequently, the bioadhesive microparticles crosslink with underlying tissues under gentle pressure. The barnacle-inspired paste can provide tough (interfacial toughness over 300 J m-2) and strong (shear and tensile strength over 70 kPa, burst pressure over 350 mmHg) hemostatic sealing of a broad range of tissues within five seconds. We validate in vitro and in vivo biocompatibility and biodegradability of the barnacle-inspired paste in rodent models. We further demonstrate potential applications of the barnacle-inspired paste for instant hemostatic sealing in ex vivo porcine aorta, in vivo rat liver and heart models.”

mPEG-PCL from PolySciTech used in development of Chrysin-delivery nanoparticles for treatment of triple-negative breast cancer

Monday, December 21, 2020, 11:00 AM ET

Triple-negative breast cancer is a type of breast cancer which lacks the three most common surface markers which are typically found on most other types of breast cancer. This form of breast cancer is highly invasive and very difficult to treat. Recently, researchers at Duksung Women’s University (Korea) used mPEG-PCL (AK001) from PolySciTech (www.polyscitech.com) to create chrysin-loaded nanoparticles for cancer therapy. This research holds promise to improve therapies against this potentially fatal disease. Read More: Kim, K., and Joohee Jung. "Upregulation of G protein-coupled estrogen receptor by chrysin-nanoparticles inhibits tumor proliferation and metastasis in triple negative breast cancer xenograft model." Frontiers in endocrinology 11 (2020). https://europepmc.org/article/pmc/pmc7522162

“Triple-negative breast cancer (TNBC) is associated with a high mortality rate among women globally. TNBC shows a high rate of recurrence and distant metastasis. Particularly, the chemotherapy is limited because hormone therapy of breast cancer is ineffective. Thus, an effective chemotherapeutic agent is needed for tumor suppression. Chrysin-nanoparticles (chrysin-NPs) were investigated for their inhibitory effect on a MDA-MB-231-derived xenograft model. To gain insight into the underlying mechanisms, we conducted human matrix metalloproteinase (MMP) array, western blot, and immunohistochemistry analysis. Furthermore, in vivo imaging was used to monitor the chemotherapeutic efficacy of chrysin-NPs in a metastasis mouse model. Chrysin-NPs significantly inhibited the proliferation of MDA-MB-231 cells via the PI3K/JNK pathway and induced cell death through the p53-apoptosis pathway, leading to delayed MDA-MB-231-derived tumor growth. Interestingly, chrysin-NPs significantly induced G protein-coupled estrogen receptor (GPER) expression, which suppresses MMPs and NF-κB expression. Chrysin-NPs acted as effective metastasis inhibitors. Our results suggest that chrysin-NPs may be used as an effective adjuvant formulation to inhibit TNBC progression.”

PLGA-Rhodamine from PolySciTech used in development of inhalable treatment for cystic fibrosis

Thursday, December 10, 2020, 4:41 PM ET

Cystic fibrosis is a progressive disease in which the airway is obstructued by thick mucus. Delivery of medicinal molecules to the lungs is difficult which makes this disease hard to treat. Recently, researchers at University of Naples and University of Campania (Italy), Used PLGA-Rhodamine (AV011) from PolySciTech (www.polyscitech.com) to create traceable, inhalable nanoparticles for fluorescent imaging and tracking of the particles as they enter the airways. This research holds promise to improve treatments against cystic fibrosis. Read more: Comegna, Marika, Gemma Conte, Andrea Falanga, Maria Marzano, Gustavo Cernera, Antonella Di Lullo, Felice Amato et al. "Assisting PNA Transport Through Cystic Fibrosis Human Airway Epithelia With Biodegradable Hybrid Lipid-Polymer Nanoparticles." (2020). https://www.researchsquare.com/article/rs-111943/latest.pdf

“Cystic Fibrosis (CF) is characterized by an airway obstruction caused by a thick mucus due to a malfunctioning Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. The sticky mucus restricts drugs in reaching target cells limiting the efficiency of treatments. The development of new approaches to enhance drug delivery to the lungs represents CF treatment's main challenge. In this work, we report the synthesis and characterization of hybrid core-shell nanoparticles (hNPs) comprising a PLGA core and a dipalmitoylphosphatidylcholine (DPPC) shell engineered for inhalation. We loaded hNPs with a 7-mer peptide nucleic acid (PNA) previously considered for its ability to modulate the posttranscriptional regulation of the CFTR gene. We also investigated the in vitro release kinetics of hNPs and their ecacy in PNA delivery across the human epithelial airway barrier using an ex vivo model based on human primary nasal epithelial cells (HNEC) from CF patients. Confocal analyses and hNPs transport assay demonstrated the ability of hNPs to overcome the mucus barrier and release their PNA cargo within the cytoplasm, where it can perform its biological function.”

PLGA from PolySciTech used in the development of nanoparticle-based cancer immunotherapy treatment

Thursday, December 10, 2020, 4:40 PM ET

An attractive target to treat cancer is to biochemically instruct the human body to mount an immune response against the cancer. This has significant advantages over conventional chemotherapy, which can indiscriminantly harm normal cells, as well as surgical and radiological procedures in which some portion of the cancer may remain and continue to grow. Recently, researchers at Korea University, and Korea Institute of Science and Technology used PLGA (AP081) from PolySciTech (www.polyscitech.com) to generate nanoparticles to control immunogenic cell death of cancer. This research holds promise to improve therapies against this disease. Read more: Choi, Yongwhan, Hong Yeol Yoon, Jeongrae Kim, Suah Yang, Jaewan Lee, Ji Woong Choi, Yujeong Moon et al. "Doxorubicin-Loaded PLGA Nanoparticles for Cancer Therapy: Molecular Weight Effect of PLGA in Doxorubicin Release for Controlling Immunogenic Cell Death." Pharmaceutics 12, no. 12 (2020): 1165. https://www.mdpi.com/1999-4923/12/12/1165

“Direct local delivery of immunogenic cell death (ICD) inducers to a tumor site is an attractive approach for leading ICD effectively, due to enabling the concentrated delivery of ICD inducers to the tumor site. Herein, we prepared doxorubicin (DOX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using different molecular weight PLGA (7000 g/mol and 12,000 g/mol), showing different drug release kinetics. The different release kinetics of DOX might differently stimulate a tumor cell-specific immune response by releasing damage-associated molecular patterns (DAMPs), resulting in showing a different antitumor response in the living body. DOX-PLGA7K NPs showed faster DOX release kinetics than DOX-PLGA12K NPs in the physiological condition. DOX-PLGA7K NPs and DOX-PLGA12K NPs were successfully taken up by the CT-26 tumor cells, subsequently showing different DOX localization times at the nucleus. Released DOX successfully lead to cytotoxicity and HMGB1 release in vitro. Although the DOX-PLGA7K NPs and DOX-PLGA12K NPs showed different sustained DOX release kinetics in vitro, tumor growth of the CT-26 tumor was similarly inhibited for 28 days post-direct tumor injection. Furthermore, the immunological memory effect was successfully established by the ICD-based tumor-specific immune responses, including DC maturation and tumor infiltration of cytotoxic T lymphocytes (CTLs). We expect that the controlled release of ICD-inducible chemotherapeutic agents, using different types of nanomedicines, can provide potential in precision cancer immunotherapy by controlling the tumor-specific immune responses, thus improving the therapeutic efficacy. Keywords: cancer immunotherapy; immunogenic cell death; nanomedicine; drug release”

PLGA-PEG-Mal from PolySciTech used in development of targeted nanoparticles for treatment of liver cancer

Wednesday, December 2, 2020, 9:17 AM ET

The liver performs multiple, critical metabolic functions which are important for sustaining life. As such, cancer forming in the liver can be a very serious situation. Recently, researchers at Anhui University of Science and Technology (China) used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create targeted nanoparticles which interact with cellular signalling molecules to inhibit the progress of liver cancer. This research holds promise to improve treatments against this potentially life-threatening disease. Read more: Shen, Jing, Wenpeng Cai, Yongfang Ma, Ruyue Xu, Zhen Huo, Li Song, Xinyin Qiu et al. "hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway." Nanoscale Research Letters 15, no. 1 (2020): 1-15. https://link.springer.com/article/10.1186/s11671-020-03451-5

“Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3+ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial–mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.”

mPEG-PLGA from PolySciTech used in development of nanotechnology for treatment of fetal diseases

Wednesday, December 2, 2020, 9:15 AM ET

Despite advances in medical technology, the ability to treat diseases within a developing fetus are very limited. Researchers at University of Antwerp (Belgium) and Cairo University (Egypt) used mPEG-PLGA (AK102) to create nanoparticles for cellular uptake testing. This research holds promise to improve medical care for early stages of development. Read more: Gonçalves, Débora R., Jo LMR Leroy, Sofie Van Hees, Inne Xhonneux, Peter EJ Bols, Filip Kiekens, and Waleed FA Marei. "Cellular uptake of polymeric nanoparticles by bovine cumulus-oocyte complexes and their effect on in vitro developmental competence." European Journal of Pharmaceutics and Biopharmaceutics (2020). https://www.sciencedirect.com/science/article/pii/S0939641120303453

“Abstract: Polymeric nanoparticles (NPs) are produced using bio-compatible and bio-degradable materials such as PLGA (Poly(lactic-co-glycolic acid)). This technology provides a valuable tool to deliver molecules to the subcellular level with a relatively low risk of cytotoxicity. However their use in the field of reproductive biotechnology is not yet scientifically substantiated. The aim of the present study was to test if PLGA NPs can be taken-up by cumulus-enclosed oocytes as a first step towards potential oocyte-targeted applications to enhance oocyte quality and fertility. We conducted a series of experiments using bovine in vitro oocyte maturation as a model to study FITC-conjugated PLGA internalization (using laser-scanning confocal microscopy) and the effect of some important physical (particle size) and chemical (conjugation with PEG) modifications. We show evidence that PLGA NPs can be taken-up by cumulus cells and to a less extent by the enclosed oocytes regardless of the NP size. The NP transfer to the oocyte appear to be transcellular (via cumulus cells and transzonal projections) and paracellular (via zona pellucida). The PLGA NPs were detected in the vicinity of the oocyte as quick as 2 h post-exposure in a protein-free medium and did not compromise cumulus cell viability nor subsequent early embryo development or embryo quality. These results suggest that PLGA NPs may have promising applications as carriers for drug or molecule delivery targeting cumulus cells and oocytes.”

Block copolymers from PolySciTech used in development of therapeutic system to reduce ocular pressure for glaucoma treatment

Wednesday, December 2, 2020, 9:14 AM ET

Increased pressure of the fluid within the eyeball can be a contributing factor to the development of glaucoma which can lead to blindness. Recently, researchers at Imperial College London used multiblock polymer (AK099) from PolySciTech (www.polyscitech.com) to deliver a novel molecule for reducing intraocular pressure. This research holds promise to improve treatments that may save eyesight. Read more: Bertrand, Jacques A., David F. Woodward, Joseph M. Sherwood, Jenny W. Wang, and Darryl R. Overby. "The role of EP2 receptors in mediating the ultra-long-lasting intraocular pressure reduction by JV-GL1." British Journal of Ophthalmology (2020). https://bjo.bmj.com/content/early/2020/11/24/bjophthalmol-2020-317762.abstract

“Abstract: Background A single application of JV-GL1 substantially lowers non-human primate intraocular pressure (IOP) for about a week, independent of dose. This highly protracted effect does not correlate with its ocular biodisposition or correlate with the once-daily dosing regimen for other prostanoid EP2 receptor agonists such as trapenepag or omidenepag. The underlying pharmacological mechanism for the multiday extended activity of JV-GL1 is highly intriguing. The present studies were intended to determine EP2 receptor involvement in mediating the long-term ocular hypotensive activity of JV-GL1 by using mice genetically deficient in EP2 receptors. Methods The protracted IOP reduction produced by JV-GL1 was investigated in C57BL/6J and EP2 receptor knock-out mice (B6.129-Ptger2tm1Brey/J; EP2KO). Both ocular normotensive and steroid-induced ocular hypertensive (SI-OHT) mice were studied. IOP was measured tonometrically under general anaesthesia. Aqueous humour outflow facility was measured ex vivo using iPerfusion in normotensive C57BL/6J mouse eyes perfused with 100 nM de-esterified JV-GL1 and in SI-OHT C57BL/6J mouse eyes that had received topical JV-GL1 (0.01%) 3 days prior. Results Both the initial 1-day and the protracted multiday effects of JV-GL1 in the SI-OHT model for glaucoma were abolished by deletion of the gene encoding the EP2 receptor. Thus, JV-GL1 did not lower IOP in SI-OHT EP2KO mice, but in littermate SI-OHT EP2WT control mice, JV-GL1 statistically significantly lowered IOP for 4–6 days. Conclusions Both the 1-day and the long-term effects of JV-GL1 on IOP are entirely EP2 receptor dependent.”

Mal-PEG-PLGA and PLGA from PolySciTech to develop Dp44mT loaded nanoparticles for treatment of brain cancer

Monday, November 23, 2020, 11:46 AM ET

Glioblastoma, a common and deadly form of brain cancer, remains very difficult to treat partially because delivery of medication to the brain tissue is very difficult. Recently, researchers at University of Houston (USA) used Mal-PEG-PLGA (AI020) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create tumor-targeting nanoparticles for treatment of brain cancer. This research holds promise to improve therapies against this deadly disease. Read more: Kang, You Jung, Claire K. Holley, Mohammad Reza Abidian, Achuthamangalam B. Madhankumar, James Connor, and Sheereen Majd. "Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation." Advanced Healthcare Materials (2020): 2001261. https://onlinelibrary.wiley.com/doi/abs/10.1002/adhm.202001261

“Abstract: The limited effectiveness of current therapeutics against malignant brain gliomas has led to an urgent need for development of new formulations against these tumors. Chelator Dp44mT (di‐2‐pyridylketone‐4,4‐dimethyl‐3‐thiosemicarbazone) presents a promising candidate to defeat gliomas due to its exceptional anti‐tumor activity and its unique ability to overcome multidrug resistance. The goal of this study is to develop a targeted nano‐carrier for Dp44mT delivery to glioma tumors and to assess its therapeutic efficacy in vitro and in vivo. Dp44mT is loaded into poly(ethylene glycol) (PEG)ylated poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) decorated with glioma‐targeting ligand Interlukin 13 (IL13). IL13‐conjugation enhanced the NP uptake by glioma cells and also improved their transport across an in vitro blood‐brain‐barrier (BBB) model. This targeted formulation showed an outstanding toxicity towards glioma cell lines and patient‐derived stem cells in vitro, with IC50 values less than 125 nM, and caused no significant death in healthy brain microvascular endothelial cells. In vivo, when tested on a xenograft mouse model, IL13‐conjugated Dp44mT‐NPs reduced the glioma tumor growth by ≈62% while their untargeted counterparts reduced the tumor growth by only ≈16%. Notably, this formulation does not cause any significant weight loss or kidney/liver toxicity in mice, demonstrating its great therapeutic potential.”

PLGA-PEG reactive intermediates from PolySciTech used in development of targeted nanoparticles for treatment of heart-disease

Tuesday, November 17, 2020, 10:44 AM ET

Although nanoparticles are often applied for cancer targeting there is nothing preventing this platform technique from being applied to other diseases. For example, nanoparticles can be applied to treating heart-disease. Recently, researchers at University of Texas at Arlington used PLGA (AP154) and PLGA-NHS (AI097) and PLGA-PEG-NHS (AI064), and PLGA-PEG-COOH (AI166) from PolySciTech (www.polyscitech.com) to create a series of nanoparticles designed to repair damage to arterial walls and prevent further heart disease. This research holds promise to improve cardiovascular care. Read more: Khang, Min Kyung, Aneetta Elizabeth Kuriakose, Tam Nguyen, Cynthia My-Dung Co, Jun Zhou, Thuy Thi Dang Truong, Kytai Truong Nguyen, and Liping Tang. "Enhanced Endothelial Cell Delivery for Repairing Injured Endothelium via Pretargeting Approach and Bioorthogonal Chemistry." ACS Biomaterials Science & Engineering (2020). https://pubs.acs.org/doi/abs/10.1021/acsbiomaterials.0c00957

“Arterial wall injury often leads to endothelium cell activation, endothelial detachment, and atherosclerosis plaque formation. While abundant research efforts have been placed on treating the end stages of the disease, no cure has been developed to repair injured and denude endothelium often occurred at an early stage of atherosclerosis. Here, a pretargeting cell delivery strategy using combined injured endothelial targeting nanoparticles and bioorthogonal click chemistry approach was developed to deliver endothelial cells to replenish the injured endothelium via a two-step process. First, nanoparticles bearing glycoprotein 1b α (Gp1bα) proteins and tetrazine (Tz) were fabricated to provide a homogeneous nanoparticle coating on an injured arterial wall via the interactions between Gp1bα and von Willebrand factor (vWF), a ligand that is present on denuded endothelium. Second, transplanted endothelium cells bearing transcyclooctene (TCO) would be quickly immobilized on the surfaces of nanoparticles via TCO:Tz reactions. In vitro binding studies under both static and flow conditions confirmed that our novel Tz-labeled Gp1bα-conjugated poly(lactic-co-glycolic acid) (PLGA) nanoparticles can successfully pretargeted toward the injured site and support rapid adhesion of endothelial cells from the circulation. Ex vivo results also confirm that such an approach is highly efficient in mediating the local delivery of endothelial cells at the sites of arterial injury. The results support that this pretargeting cell delivery approach may be used for repairing injured endothelium in situ at its early stage.”

PLGA from PolySciTech used in development of sialic acid-targeting nanoparticles for delivery of doxorubicin to cancer

Tuesday, November 17, 2020, 10:44 AM ET

Cancer therapy remains difficult as the cancer cells themselves are actually the same as normal human cells but behaving in a pathological manner. For this reason obtaining a medicine which specifically affects the cancer cells without damaging normal tissues remains difficult. Targetted therapies, designed to deliver the majority of the drug into the cancer or tumor site is one means to achieve at least some degree of this specificity. Recently, researchers at Kangwon National University (Korea) used PLGA (AP059) from PolySciTech (www.polyscitech.com) to create doxorubicin-loaded nanoparticles for cancer therapy. This research holds promise to improve the efficacy of chemotherapy in the future. Read more: Lee, Song Yi, Suyeong Nam, Ja Seong Koo, Sungyun Kim, Mingyu Yang, Da In Jeong, ChaeRim Hwang, JiHye Park, and Hyun-Jong Cho. "Possible contribution of sialic acid to the enhanced tumor targeting efficiency of nanoparticles engineered with doxorubicin." Scientific Reports 10, no. 1 (2020): 1-15. https://www.nature.com/articles/s41598-020-76778-9

“Doxorubicin (DOX)-engineered poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) including phloretin (PHL) were designed and the feasible contribution of sialic acid (SA) to the improved tumor targeting and penetration capabilities was elucidated in lung adenocarcinoma models. DOX has been clinically used as liposomal formulations after its introduction to the inner side of vehicles, however DOX is anchored in the outer surface of PLGA NPs for improved tumor penetration by interactions with SA in this study. DOX (positively charged at physiological pH) was adsorbed onto the negatively charged PLGA NPs via electrostatic interactions and consequent binding of SA (negatively charged at physiological pH) to DOX located in NPs was also elucidated. DOX layer in DOX@PLGA NPs rendered improved endocytosis and partial contribution of SA (expressed in cancer cells) to that endocytosis was demonstrated. DOX@PLGA/PHL NPs provided enhanced antiproliferation potentials in A549 cells rather than single agent (DOX or PHL)-installed NPs. In addition, DOX-SA interactions seemed to play critical roles in tumor infiltration and accumulation of DOX@PLGA NPs in A549 tumor-xenografted mouse model. All these findings support the novel use of DOX which is used for the surface engineering of NPs for improved tumor targeting and penetration.”

mPEG-PLGA from PolySciTech used in development of Piperlongumine-loaded nanoparticles for treatment of triple-negative breast cancer

Monday, November 16, 2020, 11:48 AM ET

Triple-negative breast cancer is a form of breast cancer which is difficult to treat. It is both resistant to most conventional marker-based therapies (such as HER targeted therapies) and also highly metastatic and invasive. Recently, researchers at Dalhousie University (Canada), used mPEG-PLGA (AK010) from PolySciTech (www.polyscitech.com) to deliver anti-metastatic compound Piperlongumine. This holds promise to provide for improved treatments against breast cancer. Read more: Ghassemi‑Rad, Javad, Wasundara Fernando, and David W. Hoskin. "Piperlongumine‑loaded nanoparticles inhibit the growth, migration and invasion and epithelial‑to‑mesenchymal transition of triple‑negative breast cancer cells." International Journal of Functional Nutrition 2, no. 1: 1-1. https://www.spandidos-publications.com/10.3892/ijfn.2020.11

“Metastasis and disease relapse are the major causes of morbidity and mortality among patients with triple‑negative breast cancer (TNBC). Novel therapeutics that interfere with the process of metastasis, including epithelial‑to‑mesenchymal transition (EMT), are thus urgently required. Piperlongumine (PL) is a component of the fruits of the long pepper plant (Piper longum), which are used as a spice and in traditional medicine. The present study compared the anti‑metastatic potential of free PL and PL‑loaded nanoparticles (PL‑NPs) in TNBC cells. PL was loaded into biodegradable methoxy poly(ethylene glycol)‑poly‑(lactide‑­co‑glycolic) acid copolymer NPs by thin‑film hydration. The effects of free PL and PL‑NPs on TNBC cells were compared using colorimetric MTT assays for cell growth/viability, Transwell assays for migration/invasiveness, and western blot analysis and reverse transcription‑quantitative polymerase chain reaction for expression of EMT‑associated proteins and DNA methyltransferase‑1. PL‑NPs reduced MDA‑MB‑231, MDA‑MB‑468, and BT‑549 TNBC cell growth/viability to the same extent as free PL. Treatment of the MDA‑MB‑231 cells with both PL‑NPs and free PL inhibited migration/invasiveness, reduced the expression of matrix metalloproteinase 2 and EMT‑promoting Slug, ZEB1, N‑cadherin, β‑catenin and Smad3, promoted E‑cadherin and anti‑metastatic n‑Myc downstream regulated gene 1 expression, and inhibited the expression of oncogenic DNA methyltransferase‑1. On the whole, the present study demonstrated that PL‑NPs inhibited the metastasis‑promoting activities of TNBC cells to the same extent as free PL, highlighting the feasibility of employing NPs for the delivery of PL to prevent or reduce TNBC metastasis.”

PLLA from PolySciTech used in development of cell-impregnated scaffold tissue-engineering techniques

Monday, November 16, 2020, 11:47 AM ET

A powerful tool for healing is the ability to use degradable scaffolds and cells to replace missing or damaged tissue. For this to work, a biodegradable scaffold must be prepared and then loaded with cells so that the construct can be implanted into a patient at the site of injury. Recently, researchers at Hokkaido University Hospital (Japan) used PLLA from PolySciTech (www.polyscitech.com) to create porous structures to test cell impregnation techniques. This research holds promise to improve tissue engineering. Read more: Yanagisawa, Kotaro, Seiichi Funamoto, Yoshihide Hashimoto, and Jun Negishi. "Introduction of cells into porous poly (L-lactic) acid scaffolds using impregnation techniques." Tissue Engineering (2020). https://www.liebertpub.com/doi/abs/10.1089/ten.TEC.2020.0262

“Porous materials containing cells—prepared via cell seeding on scaffolds or gelation of cell-containing solutions—have been widely studied to investigate tissue regeneration and three-dimensional cultures. However, these methods cannot introduce cells into porous materials that have low water absorption or scaffolds that require cytotoxic solvents or processes for their production. In this study, first, three different impregnation treatments conditions (vacuum, pressure, and vacuum pressure impregnation: VPI) were applied to cell suspensions to evaluate the effect of each treatment on cells. Following all three treatments, fibroblasts adhered to the cell culture dish and proliferated in the same manner as untreated cells, which confirmed that the three impregnation treatments did not affect cell function. Second, cells were introduced into a poly-L-lactic acid (PLA) scaffold, which has low water absorption, using the same impregnation treatments. The PLA scaffolds subjected to the three impregnation treatments exhibited a significantly greater amount of DNA than those subjected to immersion treatments and showed increasing amounts of DNA in the order vacuum treatment > VPI treatment > pressure treatment. Furthermore, the amount of DNA in the vacuum-treated and VPI-treated PLA scaffolds increased on the 1st, 3rd, and 5th days of culture, and it was confirmed that the cells introduced into the PLA scaffolds proliferated. These results suggest that vacuum and VPI treatments may be useful methods for introducing cells into porous materials.”

PLGA-PEG-Maleimide and mPEG-PLGA from PolySciTech used in development of nanoparticle chemotherapy for kidney cancer.

Monday, November 9, 2020, 10:37 AM ET

Delivery of medicine to renal cell carcinoma (RCC) (Kidney cancer) remains difficult as uptake to these cells is very poor. Recently, researchers at Harvard Medical School and University of California - Los Angeles used mPEG-PLGA (AK102) and PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to create a nanoparticles decorated with light-chain antibody fragments to target Kidney cancer cells. This research holds promise for improved therapies against kidney cancers in the future. Read more: Ordikhani, Farideh, Vivek Kasinath, Mayuko Uehara, Aram Akbarzadeh, Osman A. Yilmam, Li Dai, Hamza Aksu et al. "Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma." Nano Today 35 (2020): 100990. https://www.sciencedirect.com/science/article/pii/S1748013220301596

“Highlights: Light chain-conjugated nanoparticles (LC-NPs) traffic selectively to proximal tubule epithelial cells (PTECs) in the kidney. Systemic administration of LC-NPs to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Megalin expression by human renal cell carcinoma and its lymph node metastases reinforces the clinical potential of LC-NPs. Abstract: Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders. Keywords: Nanoparticles Light chain proteins Megalin Kidney Renal cell carcinoma.”

PLGA-Glucose from PolySciTech used in development of lung-cancer targeting nanoparticles

Tuesday, November 3, 2020, 2:05 PM ET

The potential to improve particle uptake to cancer cells in a selective manner provides for a unique opportunity. Recently, researchers at Qatar University used PLGA-Glucose (AP029) from PolySciTech (www.polyscitech.com) to create nanoparticles for targeting lung cancer cells. This research holds promise to improve chemotherapeutic outcomes. Read more: Benammar, Sarra, Fatima Mraiche, Jensa Mariam Joseph, and Katerina Gorachinova. "Glucose and transferrin liganded PLGA nanoparticles internalization in non-small cell lung cancer cells." Qatar University Annual Research Forum & Exhibition Poster Presentation (2020). http://qspace.qu.edu.qa/handle/10576/16810

“Introduction: Recently, after a decade of confusing results, several studies pointed out that overexpression of GLUT1 (glucose transporter 1) is a biomarker of worse prognosis in NSCLC. Nonetheless, the presence of Transferrin (Tf receptor), which is overexpressed in most cancer tissues and most lung cancers as well, in NSCLC is also an indicator of very poor prognosis. Therefore, these ligands can be used for active targeting of lung cancer cells and improved efficacy of internalization of cancer therapy using nanomedicines. Objectives: Having the background, the main goal of the project was the assessment of the influence of the glucose and transferrin ligands on the efficacy of internalization of the designed (i) glucose decorated PLGA (poly lactic-co-glycolic acid) nanoparticles (Glu-PLGA NPs) and (ii) transferrin decorated PLGA nanoparticles (Tf-PLGA NPs) in comparison to (iii) non-liganded PLGA NPs using a A549 lung cancer cells. Methods: Glu-PLGA NPs, Tf-PLGA NPs and PLGA NP - fluorescently labelled), were designed using a sonication assisted nanoprecipitation method. Further, physicochemical properties characterization (particle size analysis, zeta potential, FTIR analysis, DSC analysis), cytotoxicity evaluation using MTT test, and cell internalization studies of DTAF labelled NPs using fluorimetry in A549 NSCLC cell line were performed. Results: The results pointed to a significantly improved internalization rate of the liganded compared to PLGA NPs. Glu-PLGA NPs showed higher internalization rate compared to Tf-PLGA and PLGA NPs, in the serum-supplemented and serum-free medium even at normal levels of glucose in the cell growth medium. Conclusion: The developed nanocarriers offer unique advantages of enhanced targetability, improved cell internalization and decreased toxicity which makes them promising solution for current therapeutic limitations”

PLGA from PolySciTech used in microfluidic nanoparticle generation method development

Tuesday, November 3, 2020, 2:04 PM ET

Nanoparticles are generally created by mixing polymer dissolved in a solvent with a non-solvent for the polymer such that the polymer precipitates out into nanosized spheres. This can be achieved by a variety of methods though microfluidics enables reliable control of the mixing conditions for good reproducibility. Recently researchers at Assiut University, Badr University in Cairo (Egypt), and American University of Sharjah (UAE) used PLGA (AP154) from PolySciTech (www.polyscitech.com) to optimize nanoparticle generation using a microfluidic system. This research holds promise to improve the rapid and robust generation of nanoparticles for drug-delivery. Read more: Abdelkarim, Mahmoud, Noura H. Abd Ellah, Mahmoud Elsabahy, Mohamed Abdelgawad, and Sara A. Abouelmagd. "Microchannel geometry vs flow parameters for controlling nanoprecipitation of polymeric nanoparticles." Colloids and Surfaces A: Physicochemical and Engineering Aspects (2020): 125774. https://www.sciencedirect.com/science/article/pii/S0927775720313674

“Abstract: Channel-based microfluidics was proven to be a helpful platform for reproducible preparation of nanoparticles (NPs), where controlled mixing of fluids allows homogeneous and tuned process of NPs formation. Nanoprecipitation is a popular method for polymeric NPs formation based on controlled precipitation of a polymer upon mixing of two miscible solvents. Conventionally, flow rate, flow rate ratio and polymer concentration have been utilized to control NPs size and polydispersity. However, minimum attention has been given to the effect of channel geometry on nanoprecipitation process. In our study, we investigated the effect of channel geometry and design on the size and polydispersity index (PDI) of poly (lactic-co-glycolic) acid (PLGA) NPs. Ten different designs with varied channel length, aspect ratio, number of interfaces and channel curvature were fabricated and tested. These variations were introduced to modify the diffusion rate, the interface area or to introduce Dean flow, all of which will change the mixing time (Tmix). The effects of these variations were compared to that of different flow parameters. Change in channel length did not have a significant effect on particle size. However, increasing the diffusion area and reducing (Tmix) significantly reduced NPs’ size. Moreover, when curvature was introduced into the channel, mixing was enhanced, and particle size was decreased in a manner dependent on the velocity of the generated Dean flow. While different flow parameters continue to be the main approach for adjusting NPs properties, we demonstrate that channel geometry modification enables tuning of NPs’ size using simple designs that can be easily adapted. Keywords: Microfluidics Nanoprecipitation PLGA Polymeric nanoparticles Hydrodynamic focusing”

These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.33124804496765 seconds)


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