Tuesday, July 27, 2021

Gene delivery potential of PLA-PEG-Mal points to potential to use block polymers for mRNA vaccines

 Current strategies primarily use lipid nanoparticles and liposomes for delivery of mRNA for vaccines such as the Pfizer and Moderna vaccines against Covid. The potential for delivery of genetic material has proven itself to be a powerful tool.  Recent research has indicated the potential for gene delivery by PLA-PEG-Mal type polymeric particles as a potential therapy for irritable bowel disease. This points to the potential to use this class of polymers for delivery of mRNA and other genes as part of vaccination and other applications. Find these and other polymers at www.polyscitech.com


Verma, Priyanka, Aasheesh Srivastava, Chittur V. Srikanth, and Avinash Bajaj. "Nanoparticle-mediated gene therapy strategies for mitigating inflammatory bowel disease." Biomaterials science 9, no. 5 (2021): 1481-1502.https://pubs.rsc.org/en/content/articlehtml/2020/bm/d0bm01359e

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Abstract: Inflammatory bowel disease (IBD) is an autoimmune disorder of the gastrointestinal tract (GIT) where Ulcerative Colitis (UC) displays localized inflammation in the colon, and Crohn's Disease (CD) affects the entire GIT. Failure of current therapies and associated side-effects bring forth serious social, economic, and health challenges. The gut epithelium provides the best target for gene therapy delivery vehicles to combat IBD. Gene therapy involving the use of nucleic acid (NA) therapeutics faces major challenges due to the hydrophilic, negative-charge, and degradable nature of NAs. Recent success in the engineering of biomaterials for gene therapy and their emergence in clinical trials for various diseases is an inspiration for scientists to develop gene therapy vehicles that can be easily targeted to the desired tissues for IBD. Advances in nanotechnology have enabled the formulations of numerous nanoparticles for NA delivery to mitigate IBD that still faces challenges of stability in the GIT, poor therapeutic efficacy, and targetability. This review presents the challenges of gene therapeutics, gastrointestinal barriers, and recent advances in the engineering of nanoparticles for IBD treatment along with future directions for successful translation of nanoparticle-mediated gene therapeutics in clinics.

Nuplon Heat-Curable Resin Free Samples Available For Testing and Applications Research

In an effort to aid in combating plastic contamination of waterways and landfills, Akina, Inc. has recently developed a biodegradable, self-crosslinking resin. Intellectual property protection on the background technology for Nuplon was filed by Akina, Inc. with a priority date of June 25, 2020 and patent protection is currently pending under filing number US 2021070743. Akina, Inc. is actively seeking a partner interested in end-product applications for the Nuplon material. To that end, we’re putting Nuplon in the hands of the smartest people we know.


You.

Starting from July, 2021, samples of “pour-and-cure” heat-curable Nuplon resin are free to request from the website (https://akinainc.com/polyscitech/products/NuPlon/index.php) with only cost being shipping charges for USPS shipping. Additionally, on any order simply type “Nuplon” into the “Special Instructions” section to receive your free sample.

-Nuplon Details-

Description: Prepolymer is a set of low molecular weight oligomeric esters comprised of varying lengths of lactides and other esters combined with multifunctional alcohols and multifunctional acids. Prepolymer is a viscous liquid (Brookfield spindle, 20 ⁰C, 1000 – 3000 cP). To cure: Pour solution into desired shape of mold or onto components. Nuplon has proven to be strongly adhesive so use of either PTFE, silicone rubber, or molds coated with mold-release aid is suggested to prevent adhesion. Heat in an oven at 150 – 170 ⁰C overnight (16-24 hours) to cure. Afterwards, demold product and cut/machine to form the final shape. Adhesion: Nuplon prepolymer has strong adhesive properties and may be used to attach two components together. For this simply clamp the pieces together with the Nuplon between them and cure as described above. Post-Cure Performance: Final product is optically clear, hard plastic. Mechanical: Elastic Modulus (0.1 – 1% strain): 4.8 + 1.6 MPa, Tensile Strength: 31.0 + 19.2 MPa, Extensibility: 5.3 + 1.6 % strain, Temperature stable up to 350 ⁰C when dry. Degradation: Under normal exposure to humidity in an indoor location (20 – 25C, 30 - 80% RH) product softens after about six months and degrades after about 1-2 years forming into a soft, gel. When hydrated, will quickly become flexible after a day or two and fully degrade to non-toxic products after 2-3 months in water. For other applications and technical information visit http://www.nuplon.com/tech

PLGA from PolySciTech used in development of probiotic intestinal delivery

Humans require certain forms of bacteria in their intestine in order to provide for digestion as well as prevention of the growth of pathological bacterial. Despite the plethora of consumer products advertising probiotic contents these, in general, are poorly effective at establishing probiotic colonies in the intestines due to acidic degradation in the stomach. Recently, researchers at Pusan National University, The University of Arizona, Pohang University of Science and Technology, and Korea University used PLGA (AP121) from PolySciTech (www.polyscitech.com) as part of development of a delivery system for probiotics. This holds promise to assist people who have digestive disorders. Read more: Kim, Jihyun, Shwe Phyu Hlaing, Juho Lee, Aruzhan Saparbayeva, Sangsik Kim, Dong Soo Hwang, Eun Hee Lee et al. "Exfoliated bentonite/alginate nanocomposite hydrogel enhances intestinal delivery of probiotics by resistance to gastric pH and on-demand disintegration." Carbohydrate Polymers (2021): 118462. https://www.sciencedirect.com/science/article/pii/S0144861721008493 “Highlights: LGG was encapsulated in exfoliated bentonite/alginate nanocomposite hydrogels. Improved hydrogel pore size dramatically enhanced LGG survival at gastric pH. Complete intestinal release of LGG was observed after hydrogel disintegration. Fecal recovery of bentonite/alginate LGG was 6-fold greater than of alginate LGG. Abstract: In this study, we developed Lactobacillus rhamnosus GG (LGG)-encapsulating exfoliated bentonite/alginate nanocomposite hydrogels for protecting probiotics by delaying gastric fluid penetration into the nanocomposite and their on-demand release in the intestine. The pore size of the bentonite/alginate nanocomposite hydrogels (BA15) was two-fold smaller than that of alginate hydrogel (BA00). Following gastric pH challenge, the survival of LGG in BA15 decreased by only 1.43 log CFU/g as compared to the 6.25 log CFU/g decrease in alginate (BA00). Further, the internal pH of BA15 decreased more gradually than that of BA00. After oral administration in mice, BA15 maintained shape integrity during gastric passage, followed by appropriate disintegration within the target intestinal area. Additionally, a fecal recovery experiment in mice showed that the viable counts of LGG in BA15 were six-fold higher than those in BA00. The findings suggest the exfoliated bentonite/alginate nanocomposite hydrogel as a promising platform for intestinal delivery of probiotics. Keywords: probiotics alginate bentonite nanocomposite gastric pH resistance intestinal delivery”

PLGA-PEG-Maleimide from PolySciTech used in the development of gefitinib loaded/p28 targeted nanoparticles for lung cancer treatment

 

Delivery of medicinal molecules to cancer cells is difficult based on the ability of the medicine to specifically target towards the tumor site as well as to cross into the cancer cell. This can be improved by attaching targeting ligands to the nanoparticles to improve their uptake. Recently, researchers at University of Lisbon, University of Porto, and CESPU-Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde used PLGA-PEG-Mal (AI110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles for delivery of gefitinib to lung cancer. This research holds promise to improve treatment options for this fatal disease. Read more: Garizo, Ana Rita, Flávia Castro, Cláudia Martins, Andreia Almeida, Tiago P. Dias, Fábio Fernardes, Cristina C. Barrias, Nuno Bernardes, Arsénio M. Fialho, and Bruno Sarmento. "p28-functionalized PLGA nanoparticles loaded with gefitinib reduce tumor burden and metastases formation on lung cancer." Journal of Controlled Release (2021). https://www.sciencedirect.com/science/article/pii/S0168365921003783

“Abstract: Lung cancer is still the main cause of cancer-related deaths worldwide. Its treatment generally includes surgical resection, immunotherapy, radiotherapy, and chemo-targeted therapies such as the application of tyrosine kinase inhibitors. Gefitinib (GEF) is one of them, but its poor solubility in gastric fluids weakens its bioavailability and therapeutic activity. In addition, like all other chemotherapy treatments, GEF administration can cause damage to healthy tissues. Therefore, the development of novel GEF delivery systems to increase its bioavailability and distribution in tumor site is highly demanded. Herein, an innovative strategy for GEF delivery, by functionalizing PLGA nanoparticles with p28 (p28-NPs), a cell-penetrating peptide derived from the bacterial protein azurin, was developed. Our data indicated that p28 potentiates the selective interaction of these nanosystems with A549 lung cancer cells (active targeting). Further p28-NPs delivering GEF (p28-NPs-GEF) were able to selectively reduce the metabolic activity of A549 cells, while no impact was observed in non-tumor cells (16HBE14o-). In vivo studies using A549 subcutaneous xenograft showed that p28-NPs-GEF reduced A549 primary tumor burden and lung metastases formation. Overall, the design of a p28-functionalized delivery nanosystem to effectively penetrate the membranes of cancer cells while deliver GEF could provide a new strategy to improve lung cancer therapy. Keywords Azurin Cell penetrating peptide EGFR inhibitor Nanosized drug delivery system Active targeting Cancer therapy”

Tuesday, July 20, 2021

PLCL from PolySciTech used in development of 3D Cell-Laden microstructures for tissue engineering applications

 

Tissue regeneration and tissue engineering applies to processes whereby diseased or damaged tissue is either encouraged to heal or temporarily replaced with a construct which provides for healing. Such a technology can be applied to instances of traumatic damage where normally grafting would be necessary without requiring collection of graft tissue and the limitations associated with this. Recently, researchers at State University of New York at Buffalo used PLCL (AP034, AP074, AP067, and AP142) from PolySciTech (www.polyscitech.com) to create a 3D cell-laden structure by micromachining/manipulation of a cell-seeded 2D surface. This research holds promise to provide for tissue-engineering constructs to aid in healing of damaged tissue. Read More: Chen, Zhaowei, Nanditha Anandakrishnan, Ying Xu, and Ruogang Zhao. "Compressive Buckling Fabrication of 3D Cell‐Laden Microstructures." Advanced Science (2021): 2101027. https://onlinelibrary.wiley.com/doi/abs/10.1002/advs.202101027

“Abstract: Tissue architecture is a prerequisite for its biological functions. Recapitulating the three-dimensional (3D) tissue structure represents one of the biggest challenges in tissue engineering. Two-dimensional (2D) tissue fabrication methods are currently in the main stage for tissue engineering and disease modeling. However, due to their planar nature, the created models only represent very limited out-of-plane tissue structure. Here compressive buckling principle is harnessed to create 3D biomimetic cell-laden microstructures from microfabricated planar patterns. This method allows out-of-plane delivery of cells and extracellular matrix patterns with high spatial precision. As a proof of principle, a variety of polymeric 3D miniature structures including a box, an octopus, a pyramid, and continuous waves are fabricated. A mineralized bone tissue model with spatially distributed cell-laden lacunae structures is fabricated to demonstrate the fabrication power of the method. It is expected that this novel approach will help to significantly expand the utility of the established 2D fabrication techniques for 3D tissue fabrication. Given the widespread of 2D fabrication methods in biomedical research and the high demand for biomimetic 3D structures, this method is expected to bridge the gap between 2D and 3D tissue fabrication and open up new possibilities in tissue engineering and regenerative medicine.”

PLA from PolySciTech used in development of mussel inspired bio-adhesives

 

Adhesives are typically not environmentally friendly or biocompatible as they are manufactured of synthetic chemicals which do not provide for good interactions with cells. Recently, researchers at Purdue University used PLA (AP138) from PolySciTech (www.polyscitech.com) to create catechol modified PLA for adhesives usage and tested these for their interactions with cells. This holds promise to provide for either a bioadhesive or tissue engineering construct. Read more: Hollingshead, Sydney, Heather Siebert, Jonathan J. Wilker, and Julie C. Liu. "Cytocompatibility of a mussel‐inspired poly (lactic acid)‐based adhesive." Journal of Biomedical Materials Research Part A (2021). https://onlinelibrary.wiley.com/doi/abs/10.1002/jbm.a.37264

“Abstract: Incorporating catechols into polymers can provide strong adhesion even in moist environments, and these polymers show promise for use in several biomedical applications. Surgical adhesives must have strong bonds, be biocompatible, and function in a moist environment. Poly(lactic acid) (PLA) has a long history as a biocompatible material for hard tissue device fixation. By combining these concepts, catechol-containing poly(lactic acid) (cPLA) polymers are created that are strongly adhesive and degrade in physiological environments. Here, we evaluated the cytocompatibility of cPLA with iron(III) or periodate (IO4−) cross-linkers. Fibroblasts cultured in cPLA leachate or on cPLA films generally had slower growth and lower metabolism compared with PLA controls but no differences in viability. These results demonstrated that cPLA was not cytotoxic but that including catechols reduced cell health. When cPLA was cross-linked with periodate, cells generally had reduced metabolism, slower cell growth, and poor actin fiber formation compared with PLA. These results are attributed to the cytotoxicity of periodate since cells cultured with periodate leachate had extremely low viability. Cells grown on the films of iron-cross-linked cPLA generally had high viability and metabolism but slower proliferation than PLA controls. These results indicate that the cPLA and iron-cross-linked cPLA systems are promising materials for biomedical adhesive applications.”

Monday, July 19, 2021

PEG-PEI from PolySciTech used in development of Blood-Brain-Barrier crossing nanoparticles for gene therapy

 


Many central-nervous related diseases (Parkinson’s, Alzheimer’s, ALS, etc.) are difficult to treat due in part due to the design of the body which prevents many molecules from crossing over into the brain tissue from the blood-stream. Although the Blood-Brain-Barrier (BBB) is a necessary component to human survival as it protects the brain from potentially damaging chemicals it makes treating CNS diseases difficult. Recently, researchers at Tokyo University and Teikyo University (Japan) used PEG-PEI (AK086) from PolySciTech (www.polyscitech.com) to create gene-loaded nanoparticles for crossing the BBB. This research holds promise to improve therapy options against a range of neural diseases in the future. Read more: Endo-Takahashi, Yoko, Ryo Kurokawa, Kanako Sato, Nao Takizawa, Fumihiko Katagiri, Nobuhito Hamano, Ryo Suzuki et al. "Ternary Complexes of pDNA, Neuron-Binding Peptide, and PEGylated Polyethyleneimine for Brain Delivery with Nano-Bubbles and Ultrasound." Pharmaceutics 13, no. 7 (2021): 1003. https://www.mdpi.com/1999-4923/13/7/1003

“Abstract: In brain-targeted delivery, the transport of drugs or genes across the blood−brain barrier (BBB) is a major obstacle. Recent reports found that focused ultrasound (FUS) with microbubbles enables transient BBB opening and improvement of drug or gene delivery. We previously developed nano-sized bubbles (NBs), which were prepared based on polyethylene glycol (PEG)-modified liposomes containing echo-contrast gas, and showed that our NBs with FUS could also induce BBB opening. The aim of this study was to enhance the efficiency of delivery of pDNA into neuronal cells following transportation across the BBB using neuron-binding peptides. This study used the RVG-R9 peptide, which is a chimeric peptide synthesized by peptides derived from rabies virus glycoprotein and nonamer arginine residues. The RVG peptide is known to interact specifically with the nicotinic acetylcholine receptor in neuronal cells. To enhance the stability of the RVG-R9/pDNA complex in vivo, PEGylated polyethyleneimine (PEG-PEI) was also used. The ternary complexes composed of RVG-R9, PEG-PEI, and pDNA could interact with mouse neuroblastoma cells and deliver pDNA into the cells. Furthermore, for the in vivo experiments using NBs and FUS, gene expression was observed in the FUS-exposed brain hemispheres. These results suggest that this systemic gene delivery system could be useful for gene delivery across the BBB. Keywords: nanobubble; ultrasound; brain; gene delivery”