Monthly Archives: October 2016

PEG-PLGA from PolySciTech used as part of development of combined cancer immunotherapy/phototherapy system

A promising therapy option for cancer treatment is immunotherapy, wherein the human immune system is aided in bypassing the various protective features cancer cells typically employ to prevent themselves from being targeted as ‘non-self’ cells. This system can be combined with conventional treatment techniques to develop a robust treatment system. Recently, researchers utilized mPEG-PLGA (PolyVivo Cat# AK010) from PolySciTech (www.polyscitech.com) to generate a nanoparticle-based, combined phototherapy and immunotherapy system for treatment of cancer. This research holds promise for treatment of aggressive or drug-resistant cancers. Read more: Chen, Qian, Ligeng Xu, Chao Liang, Chao Wang, Rui Peng, and Zhuang Liu. “Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy.” Nature Communications 7 (2016): 13193. http://www.nature.com/articles/ncomms13193

“A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.”

Chiral nature of Poly-lactide demystified

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of polymers including poly(lactide). A common question I receive is about chirality as it applies to poly-lactide (PLA). If you’re like most scientists, your memories of chirality likely include staring at your right and left hands during your Organic-Chem 200 level exam trying desperately to remember which one was D and which one was L so you could put the right answer down for the test. Luckily, here, it’s simple. For poly(lactide) the important aspect of chirality applies in regards to the side-methyl unit orientation relative to the main chain. This affects the ‘tacitity’ of the polymer and in this case, pure chiral form (D or L, respectively) has the methyl units arranged on one side of the polymer chain which allows for close-stacking and crystallinity of the polymer. Conversely, the racemic mixture (D,L) has the methyl units randomly arranged which reduces crystalline formation. This minor detail strongly affects the resultant properties of the polymer as pure-chiral PLA tends to have higher mechanical stiffness but slower degradation while DL racemic PLA has more flexibility with faster degradation. PolySciTech sells both types so you can find the right one for your application.

PLGA-PEG-Mal, and PLGA-Rhodamine from PolySciTech used for development of targeted nanoparticle as part of brain cancer treatment

One critical challenge in medicine is appropriate delivery of drug molecules to the tissue or cells of interest. Recently, researchers at the Canadian Institut National de la Recherche Scientifique (INRS) utilized PLGA-Peg-Mal (PolyVivo Cat# AI052) and PLGA-Rhodamine (PolyVivo Cat# AV011) from PolySciTech to develop a glutathione decorated nanoparticle for improved curcumin delivery to neural cells. This research holds promise for improved chemotherapeutic strategies for brain cancer. Read more: Paka, Ghislain Djiokeng, and Charles Ramassamy. “Optimization of curcumin loaded-PEG-PLGA nanoparticles by GSH functionalization. Investigation of the internalization pathway in neuronal cells.” Molecular Pharmaceutics (2016). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00738

“One major challenge in the field of nanotherapeutics is to increase the selective delivery of cargo to targeted cells. Using Poly Lactic-co-Glycolic Acid (PLGA), we recently highlighted the importance of polymer composition in the biological fate of the nanodrug delivery systems. However the route of internalisation of polymeric nanoparticles (NPs) is another key component to consider in the elaboration of modern and targeted devices. For that purpose, herein, we effectively synthesized and characterised glutathione- functionalized PLGA-nanoparticles (GSH-NPs) loaded with curcumin (GSH-NPs-Cur), using thiol-maleimide click reaction and determined their physicochemical properties. We found that GSH- functionalization did not affect the drug loading efficiency (DLE), the size, the polydispersity index (PDI), the zeta potential, the release profile and the stability of the formulation. While being non-toxic, the presence of GSH on the surface of the formulations exhibits a better neuroprotective property against acrolein. The neuronal internalisation of GSH-NPs-Cur was higher than with free curcumin. In order to track the intracellular localisation of the formulations, we used a covalently attached Rhodamine (PLGA-Rhod), into our GSH-functionalized matrix. We found that GSH-functionalized matrix could easily be taken up by neuronal cells. Furthermore, we found that GSH-conjugation modifies the route of internalisation enabling them to escape the uptake through macropinocytosis and therefore avoiding the lysosomal degradation. Taken together, GSH-functionalization increases the uptake of formulations and modifies the route of internalization towards a safer pathway. This study shows that the choice of ideal ligand to develop NPs-targeting devices is a crucial step when designing innovative strategy for neuronal cells delivery.”

PEG-PLA from PolySciTech used for bacteria-mediated environmental clean-up

 

In addition to biomedical applications, several researchers have applied Polyscitech division of Akina, Inc. (www.polyscitech.com) products to environmental and industrial applications. Recently, PEG-PLA (PolyVivo cat# AK021) was used to encapsulate living Bacillus subtilis inside a double-emulsion particle. The bacteria grew nicely inside the polymer membrane which allowed permeation through the membrane. The encapsulated bacteria worked to actively convert hazardous waste-product sodium selenite into less-toxic elemental selenium. This research holds promise to improve environmental clean-up and waste-water remediation.

Read more: Barlow, Jacob, Kevin Gozzi, Chase P. Kelley, Benjamin M. Geilich, Thomas J. Webster, Yunrong Chai, Srinivas Sridhar, and Anne L. van de Ven. “High throughput microencapsulation of Bacillus subtilis in semi-permeable biodegradable polymersomes for selenium remediation.” Applied Microbiology and Biotechnology (2016): 1-10. http://link.springer.com/article/10.1007/s00253-016-7896-7

“Abstract: Encapsulating bacteria within constrained microenvironments can promote the manifestation of specialized behaviors. Using double-emulsion droplet-generating microfluidic synthesis, live Bacillus subtilis bacteria were encapsulated in a semi-permeable membrane composed of poly(ethylene glycol)-b-poly(d,l-lactic acid) (mPEG-PDLLA). This polymer membrane was sufficiently permeable to permit exponential bacterial growth, metabolite-induced gene expression, and rapid biofilm growth. The biodegradable microparticles retained structural integrity for several days and could be successfully degraded with time or sustained bacterial activity. Microencapsulated B. subtilis successfully captured and contained sodium selenite added outside the polymersomes, converting the selenite into elemental selenium nanoparticles that were selectively retained inside the polymer membrane. This remediation of selenium using polymersomes has high potential for reducing the toxicity of environmental selenium contamination, as well as allowing selenium to be harvested from areas not amenable to conventional waste or water treatment. Keywords: Microparticles Microfluidics Double-emulsion Bacteria Biofilm Selenite Nanoparticles”

PLGA from PolySciTech used as part of development of Mg-Zn-Sr implantable alloy

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Because of the great deal of characterization provided with our materials and the long, clinical history of PLGA, often these polymers are used as controls to evaluate novel surfaces against. Recently, researchers generated a novel implant alloy and evaluated it’s cytocompatibility against PLGA from PolySciTech (Cat# AP049) using HUVEC cell culture. This allowed for comparison of their novel surface against known materials as a control so as to standardize the results. This research holds promise for the development of novel implant metals such as degradable cardiac stents or other implants. Read more: Cipriano, Aaron F., Amy Sallee, Myla Tayoba, Mayra C. Cortez, Alan Lin, Ren-Guo Guan, Zhan-Yong Zhao, and Huinan Liu. “Cytocompatibility and Early Inflammatory Response of Human Endothelial Cells in Direct Culture with Mg-Zn-Sr Alloys.” Acta Biomaterialia (2016). http://www.sciencedirect.com/science/article/pii/S1742706116305475

 

“Abstract: Crystalline Mg-Zinc (Zn)-Strontium (Sr) ternary alloys consist of elements naturally present in the human body and provide attractive mechanical and biodegradable properties for a variety of biomedical applications. The first objective of this study was to investigate the degradation and cytocompatibility of four Mg-4Zn-xSr alloys (x = 0.15, 0.5, 1.0, 1.5 wt.%; designated as ZSr41A, B, C, and D respectively) in the direct culture with human umbilical vein endothelial cells (HUVEC) in vitro. The second objective was to investigate, for the first time, the early-stage inflammatory response in cultured HUVECs as indicated by the induction of vascular cellular adhesion molecule-1 (VCAM-1). The results showed that the 24-hr in vitro degradation of the ZSr41 alloys containing a β-phase with a Zn/Sr at.% ratio ∼1.5 was significantly faster than the ZSr41 alloys with Zn/Sr at.% ∼1. Additionally, the adhesion density of HUVECs in the direct culture but not in direct contact with the ZSr41 alloys for up to 24 hrs was not adversely affected by the degradation of the alloys. Importantly, neither culture media supplemented with up to 27.6 mM Mg2+ ions nor media intentionally adjusted up to alkaline pH 9 induced any detectable adverse effects on HUVEC responses. In contrast, the significantly higher, yet non-cytotoxic, Zn2+ ion concentration from the degradation of ZSr41D alloy was likely the cause for the initially higher VCAM-1 expression on cultured HUVECs. Lastly, analysis of the HUVEC-ZSr41 interface showed near-complete absence of cell adhesion directly on the sample surface, most likely caused by either a high local alkalinity, change in surface topography, and/or surface composition. The direct culture method used in this study was proposed as a valuable tool for studying the design aspects of Zn-containing Mg-based biomaterials in vitro, in order to engineer solutions to address current shortcomings of Mg alloys for vascular device applications. Statement of significance: Magnesium (Mg) alloys specifically designed for biodegradable implant applications have been the focus of biomedical research since the early 2000s. Physicochemical properties of Mg alloys make these metallic biomaterials excellent candidates for temporary biodegradable implants in orthopedic and cardiovascular applications. As Mg alloys continue to be investigated for biomedical applications, it is necessary to understand whether Mg-based materials or the alloying elements have the intrinsic ability to direct an immune response to improve implant integration while avoiding cell-biomaterial interactions leading to chronic inflammation and/or foreign body reactions. The present study utilized the direct culture method to investigate for the first time the in vitro transient inflammatory activation of endothelial cells induced by the degradation products of Zn-containing Mg alloys. Keywords: Biodegradable Magnesium Zinc Strontium alloy; Mg-Zn-Sr alloy; Human umbilical vein endothelial cells (HUVEC); Induction of vascular cell adhesion molecule-1 (VCAM-1); Early inflammatory response; Biomedical implants”

PLGA from PolySciTech used as part of antimicrobial bioadhesive development

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Recently, researchers working on development of novel bioadhesives used PLGA from PolySciTech (Cat# AP154) as a control for standardizing their cytotoxicity assay. This research holds promise for development of novel wound-closure technologies such as bioadhesives which can be used to ‘glue’ wounds shut, in a biocompatible matter, so as to reduce the need for staples and sutures. Read more: Guo, Jinshan, Gloria B. Kim, Dingying Shan, Jimin P. Kim, Jianqing Hu, Wei Wang, Fawzi G. Hamad, Guoying Qian, Elias B. Rizk, and Jian Yang. “Click chemistry improved wet adhesion strength of mussel-inspired citrate-based antimicrobial bioadhesives.” Biomaterials (2016). http://www.sciencedirect.com/science/article/pii/S014296121630552X

“Abstract: For the first time, a convenient copper-catalyzed azide-alkyne cycloaddition (CuAAC, click chemistry) was successfully introduced into injectable citrate-based mussel-inspired bioadhesives (iCMBAs, iCs) to improve both cohesive and wet adhesive strengths and elongate the degradation time, providing numerous advantages in surgical applications. The major challenge to developing such an adhesive was the mutual inhibition effect between the oxidant used for crosslinking catechol groups and the Cu(II) reductant used for CuAAC, which was successfully minimized by adding a biocompatible buffering agent typically used in cell culture, 4-(2-hydroxyethyl) -1-piperazineethanesulfonic acid (HEPES), as a copper chelating agent. Among the investigated formulations, the highest adhesion strength achieved (223.11 ± 15.94 kPa) was around 13 times higher than that of a commercially available fibrin glue (15.4 ± 2.8 kPa). In addition, dual-crosslinked (i.e. click crosslinking and mussel-inspired crosslinking) iCMBAs still preserved considerable antibacterial and antifungal capabilities that are beneficial for the bioadhesives used as hemostatic adhesives or sealants for wound management. Keywords: Click chemistry; Bioadhesives; Mussel; Citric acid; Antimicrobial”

Resorbable vascular graft development using PLCL, PLA, and PGA investigated for heart repair

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PLCL, PLA, and PGA. Recently, researchers have utilized these types of polymers to generate arterial vascular grafts that allow for good cellular growth for use in tissue engineering. This research holds promise for repairing damaged or missing heart tissue. Read more: Sugiura, Tadahisa, Shuhei Tara, Hidetaka Nakayama, Tai Yi, Yong-Ung Lee, Toshihiro Shoji, Christopher K. Breuer, and Toshiharu Shinoka. “Fast-degrading bioresorbable arterial vascular graft with high cellular infiltration inhibits calcification of the graft.” Journal of Vascular Surgery (2016). http://www.sciencedirect.com/science/article/pii/S0741521416308230

“Abstract: Objective: Bioresorbable vascular grafts are biologically active grafts that are entirely reconstituted by host-derived cells through an inflammation-mediated degradation process. Calcification is a detrimental condition that can severely affect graft performance. Therefore, prevention of calcification is of great importance to the success of bioresorbable arterial vascular grafts. The objective of this study was to test whether fast-degrading (FD) bioresorbable arterial grafts with high cellular infiltration will inhibit calcification of grafts. Methods: We created two versions of bioresorbable arterial vascular grafts, slow-degrading (SD) grafts and FD grafts. Both grafts had the same inner layer composed of a 50:50 poly(l-lactic-co-ε-caprolactone) copolymer scaffold. However, the outer layer of SD grafts was composed of poly(l-lactic acid) nanofiber, whereas the outer layer of FD grafts was composed of a combination of poly(l-lactic acid) and polyglycolic acid nanofiber. Both grafts were implanted in 8- to 10-week-old female mice (n = 15 in the SD group, n = 10 in the FD group) as infrarenal aortic interposition conduits. Animals were observed for 8 weeks. Results: von Kossa staining showed calcification in 7 of 12 grafts in the SD group but zero in the FD group (P < .01, χ2 test). The cell number in the outer layer of FD grafts was significantly higher than in the SD grafts (SD, 0.87 ± 0.65 × 103/mm2; FD, 2.65 ± 1.91 × 103/mm2; P = .02). Conclusions: The FD bioresorbable arterial vascular graft with high cellular infiltration into the scaffold inhibited calcification of grafts.”

mPEG-PCL investigated for treatment of fungal diseases

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PEG-PCL. Typically diblock mPEG-PCL is utilized primarily to form drug micelles for drug delivery. However, recently, researchers have found that mPEG-PCL selectively initiates native Staphylococcus lugdunensis to undergo fermentation, which produces acetic and isovaleric acids that act to suppress the growth of fungal Candida parapsilosis. This research holds promise for providing treatment to a wide array of fungal skin diseases. Read more: Kao, M. S., Y. Wang, S. Marito, S. Huang, and W. Z. Lin. “The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.” J Microb Biochem Technol 8 (2016): 259-265. http://www.omicsonline.org/open-access/the-mpegpcl-copolymer-for-selective-fermentation-of-staphylococcus-lugdunensis-against-candida-parapsilosis-in-the-human-microbiom-1948-5948-1000295.pdf

“Abstract: Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ɛ-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health.”