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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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Block-copolymers from PolySciTech used in the development of nano-emulsion based ultra-sound mediated noninvasive targeted drug delivery

Wednesday, November 14, 2018, 4:53 PM ET


Due to the circulatory nature of the human bloodstream, any agent introduced into the bloodstream at any location is quickly spread throughout the human body. This is good for drugs which need to be spread throughout the human body (i.e. systemic dosage) however is not very efficient for drugs whose location of action is only in one particular region. Researchers at Stanford University and Massachusetts General Hospital used several PEG-PCL, PEG-PLA, PEG-PLGA copolymers (Polyvivo AK073, AK001, AK052, AK090, AK004, and AK003) from PolySciTech (www.polyscitech.com) to generate nanoparticles with perfluorocarbons that could be activated using ultrasound. In this way the drug can be administered systemically but then released (uncaged) in the desired location of action. This research holds promise to enable targeted drug delivery with minimal side-effects. Read more: Zhong, Qian, Byung C. Yoon, Muna R. Aryal, Jeffrey B. Wang, Ananya Karthik, and Raag D. Airan. "Polymeric perfluorocarbon nanoemulsions are ultrasound-activated wireless drug infusion catheters." bioRxiv (2018): 315044. https://www.biorxiv.org/content/early/2018/09/10/315044.short

“Abstract: Catheter-based intra-arterial drug therapies have proven effective for a range of oncologic, neurologic, and cardiovascular applications. However, these procedures are limited by their invasiveness, as well as the relatively broad drug spatial distribution that is achievable with selective arterial catheterization. The ideal technique for local pharmacotherapy would be noninvasive and would flexibly deliver a given drug to any region of the body. Combining polymeric perfluorocarbon nanoemulsions with existent clinical focused ultrasound systems could in principle enable noninvasive targeted drug delivery, but it has not been clear whether these nanoparticles could provide the necessary drug loading, stability, and generalizability across a range of drugs to meet these needs, beyond a few niche applications. Here, we directly address all of those challenges and fully develop polymeric perfluorocarbon nanoemulsions into a generalized platform for ultrasound-targeted drug delivery with high potential for clinical translation. We demonstrate that a wide variety of drugs may be effectively uncaged with ultrasound using these nanoparticles, with drug loading increasing with hydrophobicity. We also set the stage for clinical translation by delineating production protocols that hew to clinical standards and yield stable and optimized ultrasound-activated drug-loaded nanoemulsions. Finally, as a new potential clinical application for these nanoemulsions, we exhibit their in vivo efficacy and performance for cardiovascular applications, by achieving local vasodilation in the highest flow vessel of the body, the aorta. This work establishes the power of polymeric perfluorocarbon nanoemulsions as a clinically-translatable platform for effective noninvasive ultrasonic drug uncaging for myriad targets in the brain and body.”

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PLGA from PolySciTech used in development of mixing system for rapid generation of nanoparticles

Wednesday, November 14, 2018, 4:53 PM ET


Nanoparticles are generally created by a controlled nanoprecipitation of polymer into a non-solvent. There are many different ways to generate nanoparticles which fundamentally differ mostly on how the mixing of polymer solution and non-solvent is accomplished. Recently, researchers at San Jose State University used PLGA (multiple types) from PolySciTech (www.polyscitech.com) to generate nanoparticles by a rapid and inexpensive technique using a 3D printed mixer. This research holds promise to enable rapid and simple creation of PLGA nanoparticles in a cost-effective manner. Read more: Le, Lan, Anuja Bokare, and Folarin Erogbogbo. "Hand Powered, cost effective, 3D printed nanoparticle synthesizer: Effects of polymer end caps, drugs, and solvents on lipid polymer hybrid nanoparticles." Materials Research Express (2018). http://iopscience.iop.org/article/10.1088/2053-1591/aaed72/meta

“Abstract: Lipid polymer hybrid nanoparticles (LPHNPs) consisting PLGA polymer as a core and DSPE-PEG as a lipid shell have been synthesized by nanoprecipitation method using hand powered, 3D printed Multi Inlet Vortex Mixer (MIVM). This method is relatively fast, simple and cost-effective as compared to other methods used for the synthesis of LPHNPs. Considering the importance of particle size in the nanoparticle mediated drug delivery, synthesis of LPHNPs with desired size has been attempted by examining various formulation variables. The synthesis conditions such as PLGA end caps, amount of drug and the type of organic solvent have been optimized to obtain LPHNPs of desired size. The formation of core-shell like structure of LPHNPs is confirmed by TEM analysis. The resulting LPHNPs were proven to have long term stability and controlled drug release properties.”

Bezwada-brand sale: use BEZWADA40 code to get 40% off Bezwada branded products purchased through PolySciTech. https://akinainc.com/polyscitech/products/polyvivo/bezdisco.php


PLGA from PolySciTech used in developing DP44mt loaded nanoparticles for cancer therapy against resistant cancers

Wednesday, November 14, 2018, 3:25 PM ET



DP44mt is a chelator molecule that binds iron and removes it from the intracellular environment. In cancer cells, this agent acts to induce cancer-cell death through upregulation of AMPK pathway and through corrupting autophagic mechanisms. One of the benefits of this therapeutic molecule is that it works against strains of cancers which are resistant to conventional chemotherapy. Recently, researchers at University of Houston purchase PLGA (AP041) from PolySciTech (www.polyscitech.com) for use in developing nanoparticles loaded with DP44mt. This research holds promise to provide for improved therapies against chemoresistant tumors. Read more: Holley, C. K., S. Alkhalifah, and S. Majd. "Fabrication and Optimization of Dp44mT-Loaded Nanoparticles." In 2018 40th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC), pp. 5733-5736. IEEE, 2018. https://ieeexplore.ieee.org/abstract/document/8513598/

“This paper describes the modulation of polymeric nanoparticle (NP) preparation to produce an optimal nanocarrier for delivery of the potent anti-tumor iron chelator, Di2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) towards application in cancer therapy. We have previously shown the potential of poly (lactic-co-glycolic acid) (PLGA) NPs as a nano-carrier for delivery of Dp44mT to malignant cells. The focus of this study is to alter the fabrication parameters to improve the characteristics of these NPs as a delivery vehicle for Dp44mT. To this end, PLGA NPs encapsulating Dp44mT are fabricated using the nanoprecipitation method with systematic variations in (i) the amount of surfactant poly (vinyl alcohol) (PVA) in aqueous phase, and (ii) the drug to polymer ratio in organic phase. The resultant NPs are characterized for size, surface potential, encapsulation efficiency, and drug release profile. Results of this study showed that increasing the PVA % (within the examined range of 0.5-4% w/v) and decreasing the Dp44mT to PLGA ratio (within the tested range of 0.0375-0.3: 1 mg/mL) both led to an increase in drug encapsulation efficiency. Focusing on the optimal PVA percentage, we found that the changes in drug to polymer ratio did not have a significant impact on the size distribution and surface potential of Dp44mT-NPs and these NPs remained in the desirable range of 80-120 nm. Lastly, the release of Dp44mT from NPs differed for different Dp44mT: PLGA ratios, providing a means to further optimize the NP formulation for future cancer treatment applications. Keywords: Drugs, Encapsulation, Polymers, Cancer, Fabrication, Nanoparticles, Iron”

Bezwada-brand sale: use BEZWADA40 code to get 40% off Bezwada branded products purchased through PolySciTech. https://akinainc.com/polyscitech/products/polyvivo/bezdisco.php


Get ‘Bezwa-more’ for your Bezwada-branded product purchase placed through PolySciTech with discount code BEZWADA40

Thursday, November 8, 2018, 2:07 PM ET




In addition to in-house manufactured materials, PolySciTech also carries products by high-quality suppliers with a focus on biomedical and polymer products. Starting from November 8 through December 31, receive an additional 40% discount off the price of Bezwada-Brand products purchased through PolySciTech using the coupon code BEZWADA40. This includes the APB*** series of high molecular weight specialty polyesters for mechanically-demanding applications. Includes polymers of glycolide, caprolactone, dioxanone, lactide, trimethylene carbonate and other monomers with focus on mechanically robust products for implants, sutures, and other applications where strength and elasticity are paramount. Also included are the AEB*** series of Poly(ethylene glycol)-diacrylates are the ideal, cross-linkable hydrogel precursor for use in micropatterning, cell-scaffolds, and biological functions. Simply mixing these polymers with an appropriate solution of commercially available and biocompatible photo-initiator generates a liquid solution which readily forms into a solid gel upon exposure to UV light. Find these products with a competitive discount at www.polyscitech.com.


mPEG-PLA and PLA-PEG-COOH from PolySciTech used in the development of nanoparticles to treat colon cancer

Tuesday, November 6, 2018, 3:42 PM ET



Galbanic acid is a naturally occurring compound extracted from Ferula (wild carrots) which has potent activity against cancer, as well as anticoagulative, antiviral, and antibacterial properties. Despite its promising biological activity, it has very poor water solubility, which limits its clinical usefulness. Recently, researchers at Mashhad University of Medical Sciences (Iran) used mPEG-PLA (Cat# AK054) and PLA-PEG-COOH (Cat# AI030) from PolySciTech (www.polyscitech.com) to create galbanic-acid loaded nanoparticles. They assayed these particles against colorectal cancer and found promising results for efficacy against this form of cancer. This research holds promise for improved therapy against cancer with lower side-effects. Read more: Afsharzadeh, Maryam, Khalil Abnous, Rezvan Yazdian–Robati, Armin Ataranzadeh, Mohammad Ramezani, and Maryam Hashemi. "Formulation and evaluation of anticancer and antiangiogenesis efficiency of PLA–PEG nanoparticles loaded with galbanic acid in C26 colon carcinoma, in vitro and in vivo." Journal of cellular physiology (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.27346

“Abstract: Galbanic acid (GBA) is an active sesquiterpene coumarin derivative, with various medicinal benefits, including anticancer properties. However, the low solubility of GBA is the main limitation of its clinical applications. In this study, we used a nanosystem based on poly (D, l‐lactide)–polyethylene glycol (PLA–PEG), for the delivery of GBA to C26 colon carcinoma cells. The physicochemical characteristics of nanoparticles (NPs) prepared by the emulsification–evaporation method were evaluated. MTT assay was used to compare the anticell proliferation of GBA and PLA–PEG–GBA against C26 cell lines. PLA–PEG‐NPs with an average size of about 140 nm had an enhanced release of GBA at a pH of 5.5 compared with a pH of 7.4. Cytotoxicity studies showed that the IC 50 of the PLA–PEG–GBA NPs (8 µM) was significantly lower than free GBA (15 µM). In the in vivo study, PLA–PEG–GBA NPs exhibited remarkable efficacy and reduced in vivo toxicity in C26 colon carcinoma tumor‐bearing female BALB/c mice. To study the antiangiogenesis effect of the NPs, tumor sections were stained with an anti CD34 antibody. The results show the CD34 (+) vessels were decreased in the GBA and PLA–PEG–GBA treated mice by more than 75% and 90%, respectively. These results suggest that the encapsulation of GBA into the PLA–PEG could potentially be used for the treatment of colorectal cancer.”


PLGA from PolySciTech used in development of nanoparticle therapy against non-small cell lung cancer

Tuesday, October 30, 2018, 4:45 PM ET


Non-small cell lung cancer is an extremely common form of cancer, leading to more than 200,000 cases in USA per year. This type of cancer typically responds poorly to chemotherapy and often becomes resistant against many chemotherapeutics. Recently, researchers at Keck Graduate Institute, St. John's University, University of La Verne, and Harvard University used PLGA (PolyVivo AP082) from PolySciTech (www.polyscitech.com) to develop erlotinib loaded nanoparticles and tested these as a means to bypass NSCLC chemotherapy resistance. This research holds promise to provide for more effective treatments against this form of cancer. Read more: Vaidya, Bhuvaneshwar, Vineela Parvathaneni, Nishant S. Kulkarni, Snehal K. Shukla, Jenna K. Damon, Apoorva Sarode, Dipti Kanabar et al. "Cyclodextrin modified erlotinib loaded PLGA nanoparticles for improved therapeutic efficacy against non-small cell lung cancer." International Journal of Biological Macromolecules (2018). https://www.sciencedirect.com/science/article/pii/S0141813018338972

“Abstract: This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells. Effect of formulation on cell cycle, apoptosis, and other markers was evaluated using flow cytometry and western blotting studies. The efficacy of optimized nanoformulation was evaluated using a clinically relevant in-vitro 3D-spheroid model. Results showed that Erlo-CD loaded nanoparticles (210 ± 8 nm in size) demonstrated 3-fold higher entrapment (61.5 ± 3.2% vs 21.9 ± 3.7% of plain erlotinib loaded nanoparticles) with ~5% loading efficiency and sustained release characteristics. Developed nanoparticles demonstrated significantly improved therapeutic efficacy against NSCLC cells in terms of low IC50 values and suppressed colony forming ability of cancer cells, increased apoptosis, and autophagy inhibition. Interestingly, 3D spheroid study demonstrated better anticancer activity of Erlo-CD nanoparticles compared to plain erlotinib. Present study has shown a premise to improve therapeutic efficacy against erlotinib-resistant lung cancer using modified nanoErlo formulations. Keywords: Erlotinib Sulfobutylether β-cyclodextrin complex Resistance lung cancer Autophagy 3D spheroids”


Fluorescent PLGA-rhodamine from PolySciTech used in development of siRNA nanoparticle therapy against glaucoma

Thursday, October 25, 2018, 3:39 PM ET



Glaucoma is a progressive disease which damages the eye’s optic nerves eventually leading to blindness if left untreated. The overgrowth of connective tissue (e.g. non-nerve based tissue for mechanical strength) is affiliated with the progression of this disease and silencing the genes associated with this may delay glaucoma’s progression. Recently, researchers at University Regensburg (Germany) used PLGA-rhodamine (PolyVivo AV011) from PolySciTech (www.polyscitech.com) as part of developing silencing RNA delivery nanoparticles as a potential therapy for glaucoma. This research holds promise to reduce blindness associated with this disease. Read more: Andrea E. Dillinger, Michaela Guter, Franziska Froemel, Gregor R. Weber, Kristin Perkumas, W. Daniel Stamer, Andreas Ohlmann, Rudolf Fuchshofer, Miriam Breunig “Intracameral Delivery of Layer‐by‐Layer Coated siRNA Nanoparticles for Glaucoma Therapy” Small 2018, 1803239. https://doi.org/10.1002/smll.201803239

“Abstract: Glaucoma is the second leading cause of blindness worldwide, often associated with elevated intraocular pressure. Connective tissue growth factor (CTGF) is a mediator of pathological effects in the trabecular meshwork (TM) and Schlemm's canal (SC). A novel, causative therapeutic concept which involves the intracameral delivery of small interfering RNA against CTGF is proposed. Layer‐by‐layer coated nanoparticles of 200–260 nm with a final layer of hyaluronan (HA) are developed. The HA‐coating should provide the nanoparticles sufficient mobility in the extracellular matrix and allow for binding to TM and SC cells via CD44. By screening primary TM and SC cells in vitro, in vivo, and ex vivo, the validity of the concept is confirmed. CD44 expression is elevated in glaucomatous versus healthy cells by about two‐ to sixfold. CD44 is significantly involved in the cellular uptake of HA‐coated nanoparticles. Ex vivo organ culture of porcine, murine, and human eyes demonstrates up to threefold higher accumulation of HA compared to control nanoparticles and much better penetration into the target tissue. Gene silencing in primary human TM cells results in a significant reduction of CTGF expression. Thus, HA‐coated nanoparticles combined with RNA interference may provide a potential strategy for glaucoma therapy.”


PLGA from PolySciTech used in creation of near-IR light responsive nanoparticles for cancer therapy

Thursday, October 25, 2018, 3:38 PM ET



Near-infrared light (wavelength between 700-1000 nm, for example T.V. remote control wavelength) has the ability to penetrate through human skin. Although this wavelength, by itself, has no therapeutic effect, it has the ability to trigger specifically designed responsive nanoparticles to cause certain events in a very tightly controlled location on the human body. Recently, researchers at Gwangju Institute of Science and Technology and Chonnam National University Medical School (Korea) utilized PLGA (PolyVivo AP036 and AP018) from PolySciTech (www.polyscitech.com) to create custom-fabricated nanoparticles which interact with NIR light to create heat and free-radicals. This technology holds promise for alternate cancer therapies based on sequential injection of nanoparticles and illumination of the tumor site. Read more: Thirunavukkarasu, Guru Karthikeyan, G. R. Nirmal, Hwangjae Lee, Mingyu Lee, Inkyu Park, and Jae Young Lee. "On-demand generation of heat and free radicals for dual cancer therapy using thermal initiator-and gold nanorod-embedded PLGA nanocomplexes." Journal of Industrial and Engineering Chemistry (2018). https://www.sciencedirect.com/science/article/pii/S1226086X18305227

“Abstract: Dual cancer therapy is an attractive strategy that can generate synergistic effects and also reduce drug-related side effects. Here, we developed multifunctional nanocomplexes capable of remote on-demand production of hyperthermia and free radicals in response to near infrared (NIR) light irradiation To this end, thermal initiator and gold nanorods were embedded in nano-sized temperature-responsive poly(lactic acid-co-glycolic acid). In vitro studies demonstrated controllable heat and radical production from the nanocomplexes with NIR and effective eradication of CT26 colon cancer cells with our nanocomplexes. Hence, our smart nanomaterial will potentially contribute precise and effective dual cancer treatment. Keywords Cancer therapy Nanomedicine Free radicals Photothermal Stimuli responsive material”


Website temporarily down

Saturday, October 20, 2018, 8:45 PM ET


October 20, 2018: akinainc.com and affiliated sites are down temporarily due to heavy winds in Indiana creating communications and power issues. We hope to have the issue resolved shortly.


mPEG-PLGA from PolySciTech used in research on immune checkpoint inhibitors for cancer therapy

Friday, October 19, 2018, 4:50 PM ET



One of the insidious features of cancer is that it has the ability to prevent the immune system from recognizing the diseased cells as ‘non-self.’ Immune checkpoint inhibitors, as chemotherapeutics, act to eliminate this feature of cancer and enable the immune system to attack it. Recently, researchers from Harvard Medical School, Hamad Bin Khalifa University (Qatar), and University of California, Los Angeles, used mPEG-PLGA (PolyVivo AK102) from PolySciTech (www.polyscitech.com) to develop anti-PD-1 loaded nanoparticles and investigated the effect of these nanoparticles on cancer therapy. This research holds promise for better understanding of immunotherapy cancer treatment options. read more: Farideh Ordikhani, Mayuko Uehara, Vivek Kasinath, Li Dai, Siawosh K. Eskandari, Baharak Bahmani, Merve Yonar, Jamil R. Azzi, Yousef Haik, Peter T. Sage, George F. Murphy, Nasim Annabi, Tobias Schatton, Indira Guleria, and Reza Abdi “Targeting antigen-presenting cells by anti–PD-1 nanoparticles augments antitumor immunity” JCI Insight. 2018;3(20):e122700 https://insight.jci.org/articles/view/122700

“Recent studies in cancer research have focused intensely on the antineoplastic effects of immune checkpoint inhibitors. While the development of these inhibitors has progressed successfully, strategies to further improve their efficacy and reduce their toxicity are still needed. We hypothesized that the delivery of anti–PD-1 antibody encapsulated in PLGA nanoparticles (anti–PD-1 NPs) to the spleen would improve the antitumor effect of this agent. Unexpectedly, we found that mice treated with a high dose of anti–PD-1 NPs exhibited significantly higher mortality compared with those treated with free anti–PD-1 antibody, due to the overactivation of T cells. Administration of anti–PD-1 NPs to splenectomized LT-α–/– mice, which lack both lymph nodes and spleen, resulted in a complete reversal of this increased mortality and revealed the importance of secondary lymphoid tissues in mediating anti–PD-1–associated toxicity. Attenuation of the anti–PD-1 NPs dosage prevented toxicity and significantly improved its antitumor effect in the B16-F10 murine melanoma model. Furthermore, we found that anti–PD-1 NPs undergo internalization by DCs in the spleen, leading to their maturation and the subsequent activation of T cells. Our findings provide important clues that can lead to the development of strategies to enhance the efficacy of immune checkpoint inhibitors.”


PLGA-PEG-COOH from PolySciTech used in development of nucleolin-targeting nanoparticles

Wednesday, October 17, 2018, 4:50 PM ET



Often, in cancer, nucleolin is overexpressed on the surface which allows it to be used as a target for drug-delivery. Recently, researchers at Tabriz University of Medical Sciences (Iran) utilized PLGA-PEG-COOH (PolyVivo AI076) from PolySciTech (www.polyscitech.com) to generate anti-nucleolin decorated nanoparticles for cancer targeting. This research holds promise for improved chemotherapeutics. Read more: Mosafer, Jafar, and Ahad Mokhtarzadeh. "Cell Surface Nucleolin as a Promising Receptor for Effective AS1411 Aptamer-Mediated Targeted Drug Delivery into Cancer Cells." Current drug delivery 15, no. 9 (2018): 1323-1329. https://www.ingentaconnect.com/contentone/ben/cdd/2018/00000015/00000009/art00013

“Background: One of the major abundant proteins in the nucleous is nucleolin that overexpressed on the cytoplasmic membrane of malignant and endothelial cells and makes it as a promising condidate for targeted drug delivery. Objectives: In this study, doxorubicin (Dox) as a chemotherapy drug was entrapped into the Poly lacticco- glycolic acid (PLGA)-based nanoparticles (NPs). Then, the targeting ability of anti nucleolin AS1411 aptamer-targeted Dox-encapsulated PLGA-based NPs (AS1411-NPs) was investigated in high nucleolin-expressing C26 colon carcinoma and rat C6 glioma cell lines compared with low nucleolin expressing mouse L929 cell line. Methods: We recently first assessed the existence of cell surface nucleolin of these three different cell lines by immunocytochemistry method. We found that a large amount of nucleolin was localized in the cytoplasmic membrane of C26 and C6 cell lines, with a very smaller amount on the surface of L929 cell line. Results: As a result, more rapidly internalization of AS1411-NPs into the C26 and C6 cells compared with L929 cells was verified. Conclusion: We think that AS1411-NPs, as a ligand, first bind to nucleolin, as a receptor, and then the receptor-ligand complex is more efficiently incorporated into the high nucleolin-expressing cell lines through receptor-mediated endocytosis pathway. Keywords: AS1411 aptamer; Nucleolin; PLGA; doxorubicin; internalization; targeted delivery”


mPEG-PLGA and PLGA from PolySciTech used in development of nanoparticle therapy for brain cancer

Tuesday, October 16, 2018, 4:03 PM ET



Glioblastoma is a common form of brain cancer which is typically fatal. The treatment of cancer requires the use of medicines that typically have very severe side-effects and a very narrow therapeutic window. Recently, a kinase inhibitor has shown promise for cancer therapy, however, it failed due to toxicity issues during phase 1 clinical trials. The ability to deliver this molecule in a more controlled manner may reduce the toxicity issues and allow for it to be used as a therapy. Recently, researchers from the University of Massachusetts and the Dana-Farber Cancer Institute used mPEG-PLGA (AK027) and PLGA (AP041) from PolySciTech (www.polyscitech.com) to create nanoparticles loaded with a novel kinase inhibitor as a prototype therapy for brain-cancer. These nanoparticles allow for dosing smaller concentrations in a more time-controlled manner. This research holds promise to provide for improved therapies against this fatal disease. Read more: Velpurisiva, Praveena, Brandon Piel, Jack Lepine, and Prakash Rai. "GSK461364A, a Polo-Like Kinase-1 Inhibitor Encapsulated in Polymeric Nanoparticles for the Treatment of Glioblastoma Multiforme (GBM)." Bioengineering 5, no. 4 (2018): 83. http://www.mdpi.com/2306-5354/5/4/83

“Abstract: Glioblastoma Multiforme (GBM) is a common primary brain cancer with a poor prognosis and a median survival of less than 14 months. Current modes of treatment are associated with deleterious side effects that reduce the life span of the patients. Nanomedicine enables site-specific delivery of active pharmaceutical ingredients and facilitates entrapment inside the tumor. Polo-like kinase 1 (PLK-1) inhibitors have shown promising results in tumor cells. GSK461364A (GSK) is one such targeted inhibitor with reported toxicity issues in phase 1 clinical trials. We have demonstrated in our study that the action of GSK is time dependent across all concentrations. There is a distinct 15-20% decrease in cell viability via apoptosis in U87-MG cells dosed with GSK at low concentrations (within the nanomolar and lower micromolar range) compared to higher concentrations of the drug. Additionally, we have confirmed that PLGA-PEG nanoparticles (NPs) containing GSK have shown significant reduction in cell viability of tumor cells compared to their free equivalents. Thus, this polymeric nanoconstruct encapsulating GSK can be effective even at low concentrations and could improve the effectiveness of the drug while reducing side effects at the lower effective dose. This is the first study to report a PLK-1 inhibitor (GSK) encapsulated in a nanocarrier for cancer applications. Keywords: GSK461364A; Glioblastoma Multiforme; polymeric nanoparticles; cytotoxicity; enhanced permeability and retention; polo-like kinase inhibitor; oncology; oncomedicine; U-87 MG”


PLA-PEG-PLA thermogel from PolySciTech used in recent patent on ocular controlled-release system

Wednesday, October 10, 2018, 12:25 PM ET



Delivery of medications into the ocular region is necessary for a wide range of diseases, but also challenging. Recently, researchers for Biohealthways, Inc. used PLA-PEG-PLA thermogel (PolyVivo AK100) from PolySciTech (www.polyscitech.com) in development of patent technology for delivery of ocular medicines. This research holds promise to treat a wide range of ocular diseases. Read more: Pan, David. "Biodegrading implantable ocular sustained release drug delivery system." U.S. Patent Application 15/924,318, filed September 20, 2018 .https://patents.google.com/patent/US20180264179A1/en

“Abstract: An ocular implant is provided for an intraocular delivery of a therapeutic biologic agent. The implant may be used intracamerally or intravitreally. The implant may include a sustained-release biodegradable core and a biodegradable shell, wherein the shell has a longer biodegradable half-life than the core. The core may include a biodegradable gel medium, an active therapeutic biologic agent, and a biologic stabilizer. Upon insertion into the anterior chamber or vitreous body of an eye, the therapeutic biologic agent is released over an extended period, that may range from one day to one year. The therapeutic biologic agent may be, for example, tissue-plasminogen activator, an anti-VEGF agent, or another biopharmaceutical. The biodegradable implant may completely dissolve after implantation and need not be removed.”


300th article! Mal-PEG-PLGA and mPEG-PLGA from PolySciTech used in development of immune-targeting nanoparticles to reduce organ rejection

Wednesday, October 10, 2018, 12:18 PM ET



Organ transplantation is a life-saving surgical technique in which the organs or tissues from a donor can be placed into a recipient to replace damaged or missing organs. Organ rejection occurs when the recipient’s immune system recognizes the transplanted organs or tissue as ‘non-self’ and launches an immune response against them. Recently researchers at Johns Hopkins University School of Medicine, Harvard Medical School, Tufts University, Universite de Lille (France), Hamad bin Khalifa University (Qatar), and University of Maryland used mPEG-PLGA (AK102) and Mal-PEG-PLGA (A110) from PolySciTech (www.polyscitech.com) to develop targeted nanoparticles to prevent immune-rejection of the transplanted tissue. This technology holds promise to prevent the potentially fatal incidence of tissue rejection. Furthermore, this article officially marks the 300th publication citing PolySciTech as the source of their research products since the first article published in 2011. Read more: Bahmani, Baharak, Mayuko Uehara, Liwei Jiang, Farideh Ordikhani, Naima Banouni, Takaharu Ichimura, Zhabiz Solhjou et al. "Targeted delivery of immune therapeutics to lymph nodes prolongs cardiac allograft survival." The Journal of clinical investigation 128, no. 11 (2018). https://www.jci.org/articles/view/120923

“The targeted delivery of therapeutic drugs to lymph nodes (LNs) provides an unprecedented opportunity to improve the outcomes of transplantation and immune-mediated diseases. The high endothelial venule is a specialized segment of LN vasculature that uniquely expresses peripheral node addressin (PNAd) molecules. PNAd is recognized by MECA79 mAb. We previously generated a MECA79 mAb–coated microparticle (MP) that carries tacrolimus. Although this MP trafficked to LNs, it demonstrated limited therapeutic efficacy in our transplant model. Here, we have synthesized a nanoparticle (NP) as a carrier of anti-CD3, and optimized the conjugation strategy to coat the NP surface with MECA79 mAb (MECA79-anti-CD3-NP) to enhance LN accumulation. As compared with nonconjugated NPs, a significantly higher quantity of MECA79-NPs accumulated in the draining lymph node (DLN). Many MECA79-NPs underwent internalization by T cells and dendritic cells within the LNs. Short-term treatment of murine cardiac allograft recipients with MECA79-anti-CD3-NP resulted in significantly prolonged allograft survival in comparison with the control groups. Prolonged graft survival following treatment with MECA79-anti-CD3-NP was characterized by a significant increase in intragraft and DLN Treg populations. Treg depletion abrogated the prolongation of heart allograft survival. We believe this targeted approach of drug delivery could redefine the methods of administering immune therapeutics in transplantation.”


PLA from PolySciTech used in investigation of enzymatic degradation of plastics

Wednesday, October 10, 2018, 12:13 PM ET



An environmental hazard which has been growing over the years is the accumulation of plastic waste. Since conventional plastics, such as polyethylene and polypropylene, do not degrade easily, they remain in the ocean and other places for a long time. Recently, researchers from University of Toronto utilized a series of PLA’s (AP005, AP004, AP047) from PolySciTech (www.polyscitech.com) to investigate the role of environmental enzymes in breaking down PLA, a potential replacement for other plastics which can biodegrade under environmental conditions. This research holds promise for improved degradability of polyesters to reduce environmental burdens. Read more: Hajighasemi, Mahbod, Anatoli Tchigvintsev, Boguslaw P. Nocek, Robert Flick, Ana Popovic, Tran Hai, Anna N. Khusnutdinova et al. "Screening and characterization of novel polyesterases from environmental metagenomes with high hydrolytic activity against synthetic polyesters." Environmental Science & Technology (2018). https://pubs.acs.org/doi/abs/10.1021/acs.est.8b04252

“Abstract: The continuous growth of global plastics production, including polyesters, has resulted in increasing plastic pollution and subsequent negative environmental impacts. Therefore, enzyme-catalyzed depolymerization of synthetic polyesters as a plastics recycling approach has become a focus of research. In this study, we screened over 200 purified uncharacterized hydrolases from environmental metagenomes and sequenced microbial genomes and identified at least 10 proteins with high hydrolytic activity against synthetic polyesters. These include the metagenomic esterases MGS0156 and GEN0105, which hydrolyzed polylactic acid (PLA), polycaprolactone, as well as bis(benzoyloxyethyl)-terephthalate. With solid PLA as a substrate, both enzymes produced a mixture of lactic acid monomers, dimers, and higher oligomers as products. The crystal structure of MGS0156 was determined at 1.95 Å resolution and revealed a modified α/β hydrolase fold, with a lid domain and highly hydrophobic active site. Mutational studies of MGS0156 identified the residues critical for hydrolytic activity against both polyester and monoester substrates, with two-times higher polyesterase activity in the MGS0156 L169A mutant protein. Thus, our work identified novel, highly active polyesterases in environmental metagenomes and provided molecular insights into their activity, thereby augmenting our understanding of enzymatic polyester hydrolysis.”


Fluorescent-PLGA and PLGA-PEG-Mal from PolySciTech used in development of gastric/colorectal-cancer targeting nanoparticles.

Monday, October 1, 2018, 7:21 PM ET



Cancer cells present a variety of surface proteins and markers which can be used to both differentiate them from normal, healthy cells as well as useful as targets for treating the cancer cell. In this way, the antibody counter-part to the surface marker can be conjugated to a nanoparticle making it selectively ‘sticky’ to the cancer cell. This is a powerful technique to improve the efficacy of drugs against cancer cells with less toxicity against healthy cells. Recently, researchers at Universidade do Porto, Universitário de Ciências da Saúde (Portugal), and Queen’s University Belfast (UK) used PLGA-FKR648 (PolyVivo AV015) and PLGA-PEG-Mal (PolyVivo AI110) from PolySciTech (www.polyscitech.com) to generate fluorescent, targeted nanoparticles for treatment of gastric and colorectal cancer. This research holds promise for improved therapies against this difficult to treat and often fatal disease. Read more: Kennedy, Patrick J., Flavia Sousa, Daniel Ferreira, Carla Pereira, Marika Nestor, Carla Oliveira, Pedro L. Granja, and Bruno Sarmento. "Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6." Acta Biomaterialia (2018). https://www.sciencedirect.com/science/article/pii/S1742706118305725

“Abstract: Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized for the first time poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs display spherical morphology around 300 nm and are negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 µg/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and long-term stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6+ carcinomas. Statement of Significance: The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. NPs strongly bind to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences, for the first time, on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration. Keywords: Human CD44v6 Targeted drug delivery Antibody-conjugated nanoparticles PLGA nanoparticles Theranostics”


PLGA from PolySciTech used in development of blood-brain-barrier penetrating nanoparticle-based treatment of brain cancer

Thursday, September 27, 2018, 1:53 PM ET



Brain cancer is often deadly and very difficult to treat partially due to the presence of the blood-brain-barrier, which prevents medicine from crossing over into the brain cavity. One means of delivering drug into this region is to generate small particles bearing specific signaling moieties such as transferrin or cell-penetrating peptide which triggers the endothelial lining of the brain to allow the particles to pass. Recently, researchers at North Dakota State University used PLGA (Polyvivo AP022) from PolySciTech (www.polyscitech.com) as part of their development of custom liposomal nanoparticles to deliver chemotherapeutic agents across the blood-brain-barrier. This research holds promise for improved therapies for brain-cancer in the future. Read More: Lakkadwala, Sushant, and Jagdish Singh. "Co-delivery of Doxorubicin and Erlotinib through Liposomal Nanoparticles for Glioblastoma Tumor Regression Using an In Vitro Brain Tumor Model." Colloids and Surfaces B: Biointerfaces (2018). https://www.sciencedirect.com/science/article/pii/S0927776518306581

“Abstract: Glioma is a highly malignant tumor that starts in the glial cells of brain. Tumor cells reproduce quickly and infiltrate rapidly in high grade glioma. Permeability of chemotherapeutic agents into brain is restricted owing to the presence of blood brain barrier (BBB). In this study, we developed a dual functionalized liposomal delivery system for efficient transport of chemotherapeutics across BBB for the treatment of glioma. Liposomes were surface modified with transferrin (Tf) for receptor targeting, and cell penetrating peptide PFVYLI (PFV) to increase translocation of doxorubicin (Dox) and Erlotinib (Erlo) across the BBB into glioblastoma (U87) tumor cells. In vitro cytotoxicity and hemolysis studies were performed to assess biocompatibility of liposomal nanoparticles. Cellular uptake studies demonstrated efficient internalization of Dox and Erlo in U87, brain endothelial (bEnd.3), and glial cells. In addition, dual functionalized liposomes showed significantly (p < 0.05) higher apoptosis in U87 cells. Significantly (p < 0.05) higher translocation of dual functionalized liposomes across the BBB and delivering chemotherapeutic drugs to the glioblastoma tumor cells inside PLGA-Chitosan scaffold resulted in approximately 52% tumor cell death, using in vitro brain tumor model. Highlights: Transferrin-PFVYLI (Tf-PFV) liposomes were prepared by post-insertion method. Tf-PFV liposomes showed Tf receptor targeting and enhanced cell penetration. Cytotoxicity and hemolysis studies exhibited biocompatibility of the liposomes. Increased transport of Tf-PFV liposomes across the barrier into tumor-scaffold. Tf-PFV liposomes demonstrated excellent anti-tumor efficacy. Keywords: Dual-functionalized liposomes Glioblastoma In vitro brain tumor model Co-delivery Blood brain barrier”


PLGA-PEG-Mal from PolySciTech used in development of non-small cell lung cancer therapeutic nanoparticles

Monday, September 24, 2018, 8:45 PM ET



Microfluidic emulsification is a manufacturing technique which holds promise to enable rapid and robust generation of nanoparticles or micelles. Higher uniformity, size control, and drug loading can be achieved by this technique relative to conventional methods, such as emulsion or dialysis techniques. Recently, researchers from Tongji University (China) used Mal-PEG-PLGA (PolyVivo AI110) to create nanoparticles both by dialysis and microfluidic techniques. These particles were targeted by conjugating on RGD ligands and the resultant particles were tested for loading, size, and targeting capabilities. This research holds promise to provide for improved cancer therapeutics in the future. Read more: Bao, Yuchen, Qinfang Deng, Yongyong Li, and Songwen Zhou. "Engineering docetaxel-loaded micelles for non-small cell lung cancer: a comparative study of microfluidic and bulk nanoparticle preparation." RSC Advances 8, no. 56 (2018): 31950-31966. https://pubs.rsc.org/en/content/articlehtml/2018/ra/c8ra04512g

“Abstract: Bulk preparation of micelles has the drawbacks of facile formation of large aggregates and heterogeneous particle size distribution. Microfluidic technology has shown clear potential to address these challenges for robust nanomedicine applications. In this study, docetaxel-loaded PLGA-PEG-Mal-based micelles were prepared by microfluidics and dialysis methods and their physicochemical properties were analyzed. The biological behaviors of these micelles were also investigated in the non-small cell lung cancer (NSCLC) cell line A549 in vitro as well as in vivo. Encouragingly, the mean particle size of the micelles prepared by microfluidics (DMM) was smaller, with an average size of 72 ± 1 nm and a narrow size distribution with a polydispersity index (PDI) of 0.072; meanwhile, micelles prepared by the dialysis method (DMD) had larger particle sizes (range, 102 to 144 nm) and PDIs (up to 0.390). More importantly, significantly high drug loading was achieved using the microfluidic process. The IC50 value of DMM was lower than that of DMD. Whole-body fluorescence imaging of live mice showed that DMM achieved higher accumulation in tumors compared with DMD. DMM showed superior antitumor efficacy, with a tumor inhibition rate of 91.5%. Moreover, pathological histology analysis revealed that no evident biological toxicity was caused by the micelles. In addition, Arg-Gly-Asp (RGD) was employed as a targeting agent on the basis of DMM to prepare targeting micelles, and the targeting micelles exhibited stronger cytotoxicity and obvious antitumor efficacy. In conclusion, DMM may have obvious clinical advantages for the treatment of NSCLC due to its optimized physiochemical properties. Therefore, microfluidic technology-based micelles are a promising platform as an effective drug delivery system for incorporating anticancer agents.”


mPEG-PLGA from PolySciTech used to create peptide-loaded nanoparticles to prevent bacterial biofilm

Tuesday, September 18, 2018, 9:16 PM ET



One of the problematic features of bacteria in the oral cavity is their tendency to adhere strongly to one another forming surfaces known as ‘biofilm.’ Biofilm is comprised of layers of bacteria all attached to one another that is very difficult to treat or remove. Recently, researchers at The University of Louisville used mPEG-PLGA (Polyvivo AK026) from PolySciTech (www.polyscitech.com) to create BAR peptide loaded nanoparticles that prevent bacteria from sticking to one another. These particles were found to be effective at preventing biofilm formation. This research holds promise to improve periodontal treatments. Read more: Mahmoud, Mohamed Y., Donald R. Demuth, and Jill M. Steinbach-Rankins. "BAR-encapsulated nanoparticles for the inhibition and disruption of Porphyromonas gingivalis–Streptococcus gordonii biofilms." Journal of Nanobiotechnology 16, no. 1 (2018): 69. https://link.springer.com/article/10.1186/s12951-018-0396-4

“Abstract: Background: Porphyromonas gingivalis adherence to oral streptococci is a key point in the pathogenesis of periodontal diseases (Honda in Cell Host Microbe 10:423–425, 2011). Previous work in our groups has shown that a region of the streptococcal antigen denoted BAR (SspB Adherence Region) inhibits P. gingivalis/S. gordonii interaction and biofilm formation both in vitro and in a mouse model of periodontitis (Daep et al. in Infect Immun 74:5756–5762, 2006; Daep et al. in Infect immun 76:3273–3280, 2008; Daep et al. in Infect Immun 79:67–74, 2011). However, high localized concentration and prolonged exposure are needed for BAR to be an effective therapeutic in the oral cavity. Methods: To address these challenges, we fabricated poly(lactic-co-glycolic acid) (PLGA) and methoxy-polyethylene glycol PLGA (mPEG-PLGA) nanoparticles (NPs) that encapsulate BAR peptide, and assessed the potency of BAR-encapsulated NPs to inhibit and disrupt in vitro two-species biofilms. In addition, the kinetics of BAR-encapsulated NPs were compared after different durations of exposure in a two-species biofilm model, against previously evaluated BAR-modified NPs and free BAR. Results: BAR-encapsulated PLGA and mPEG-PLGA NPs potently inhibited biofilm formation (IC50 = 0.7 μM) and also disrupted established biofilms (IC50 = 1.3 μM) in a dose-dependent manner. In addition, BAR released during the first 2 h of administration potently inhibits biofilm formation, while a longer duration of 3 h is required to disrupt pre-existing biofilms. Conclusions These results suggest that BAR-encapsulated NPs provide a potent platform to inhibit (prevent) and disrupt (treat) P. gingivalis/S. gordonii biofilms, relative to free BAR. Keywords Polymer nanoparticle Poly(lactic-co-glycolic acid) Peptide delivery Drug delivery Porphyromonas gingivalis Streptococcus gordonii Periodontal disease Oral biofilm”


PLCL and PLGA-NH2 from PolySciTech used in development of cartilage repair tissue scaffold

Tuesday, September 18, 2018, 9:14 PM ET


Cartilage heals poorly as it is poorly vascularized, grows slowly, and has critical mechanical properties. Cartilage is commonly damaged by arthritic disease and trauma. Recently, researchers from the University of Maryland and National Institute of Standards and Technology used PLCL (AP179) and PLGA-NH2 (AI125) from PolySciTech (www.polyscitech.com) to design a 3D printed scaffold for repairing cartilage. This technology holds promise for improved repair and healing of joint tissues. Read more: Guo, Ting, Maeesha Noshin, Hannah B. Baker, Evin Taskoy, Sean J. Meredith, Qinggong Tang, Julia P. Ringel et al. "3D Printed Biofunctionalized Scaffolds for Microfracture Repair of Cartilage Defects." Biomaterials (2018). https://www.sciencedirect.com/science/article/pii/S0142961218306598

“Abstract: While articular cartilage defects affect millions of people worldwide from adolescents to adults, the repair articular cartilage defects still remains challenging due to the limited endogenous regeneration of the tissue and poor integration with implantations. In this study, we developed a 3D-printed scaffold functionalized with aggrecan that supports the cellular fraction of bone marrow released from microfracture, a widely used clinical procedure, and demonstrated tremendous improvement of regenerated cartilage tissue quality and joint function in a lapine model. Optical coherence tomography (OCT) revealed doubled thickness of the regenerated cartilage tissue in the group treated with our aggrecan functionalized scaffold compared to standard microfracture treatment. H&E staining showed 366 ± 95 chondrocytes present in the unit area of cartilage layer with the support of bioactive scaffold, while conventional microfracture group showed only 112 ± 26 chondrocytes. The expression of type II collagen appeared almost 10 times higher with our approach compared to normal microfracture, indicating the potential to overcome the fibro-cartilage formation associated with current microfracture approach. The therapeutic effect was also evaluated at joint function level. The mobility was evaluated using a modified Basso, Beattie and Bresnahan (BBB) scale. While the defect control group showed no movement improvement over the course of study, all experimental groups showed a trend of increasing scores over time. The present work developed an effective method to regenerate critical articular defects by combining a 3D-printed therapeutic scaffold with the microfracture surgical procedure. This biofunctionalized acellular scaffold has great potential to be applied as a supplement for traditional microfracture to improve the quality of cartilage regeneration in a cost and labor effective way. Key Words: aggrecan scaffold extrusion 3D printing microfracture articular cartilage Poly(L-Lactide-co-ε-Caprolactone) custom fabrication”


Website

Friday, September 14, 2018, 8:41 AM ET


Akina's website was down last night due to necessary repairs on our server. The website is back up and running now and we are business as usual. Thanks for your patience.


PEG-Folate from PolySciTech used in development of theranostic particle for breast cancer treatment

Monday, September 10, 2018, 8:33 PM ET



Theranostics refers to a method of treatment for cancer in which the applied therapy both treats and diagnosis the cancer. Typically, this relies on targeted nanoparticles which have specialized fluorescent properties in order to render cancer visible as well as deliver a therapeutic agent to the cancer cells to prevent their growth and proliferation. Recently, researchers at Wrocław University used Folate-PEG-NH2 (PolyVivo AE005) from PolySciTech (www.polyscitech.com) to develop theranostic nanoparticles against breast cancer. This research holds promise to provide for improved therapies against this difficult to treat and potentially fatal disease. Read more: Wawrzyńczyk, Dominika, Urszula Bazylińska, Łukasz Lamch, Julita Kulbacka, Anna Szewczyk, Artur Bednarkiewicz, Kazimiera Wilk, and Marek Samoć. "FRET Activated Processes in Smart Nanotheranostics Fabricated in a Sustainable Manner." ChemSusChem (2018). https://onlinelibrary.wiley.com/doi/abs/10.1002/cssc.201801441

“Abstract: The multilayer nanocarriers loaded with optically activated payloads are gaining increasing attention, due to their anticipated crucial role for providing new mechanisms of energy transfers in the health-oriented applications, as well as for energy storage and environment protection. The combination of careful selection of optical components for efficient Förster Resonance Energy Transfer, and surface engineering of the nanocarriers, allowed us to synthesize and characterize novel theranostic nanosystems for diagnosis and therapy of deep-seated tumors. The cargo, constrained within the oil core of the nanocapsules, composed of NaYF4:Tm+3,Yb+3 up-converting nanoparticles together with a second-generation porphyrin-based photosensitizing agent – Verteporfin, assured requisite diagnostic and therapeutic functions under near-infrared laser excitation. The outer polyaminoacid shell of the nanocapsules was functionalized with a ligand − poly(L-glutamic acid) functionalized by PEG-ylated folic acid − to ensure both “stealth” effect and active targeting towards human breast cancer cells. The preparation criteria of all nanocarriers building blocks meet the requirements for sustainable and green chemistry practices. The multifunctionality of the proposed nanocarriers is a consequence of both the surface functionalized organic exterior part, that was accessible for selective accumulation in cancer cells, and the hydrophobic optically active interior, which shows phototoxicity upon irradiation within the first biological window.”


PLGA from PolySciTech used in development of magnetic nanoparticles for brain cancer therapy

Wednesday, September 5, 2018, 12:02 PM ET



Have you ever pushed a magnet on one side of a table around using another magnet from beneath the table? If you have, it is unlikely you considered this as an option for treatment of brain cancer, however this is a technique which is being applied for crossing the notoriously difficult blood-brain-barrier. One of the insidious features of brain cancer is that the disease primarily occupies the ‘brain’ side of the blood-brain-barrier. Due to the limited uptake of medicines in the blood-stream into the brain, it is very difficult to administer therapeutics to brain cancer in patients. Recently, researchers at Iran University of Medical Sciences and University of Tehran (Iran) utilized PLGA (AP040) from PolySciTech (www.polyscitech.com) to create nano-graphene-oxide loaded nanoparticles with magnetic functionality. By carefully controlling magnetic fields, they were able to improve the particle capacity to deliver medicine across the blood-brain-barrier. This research holds promise for improved therapy for glioblastoma and other brain-cancer forms. Read more: Shirvalilou, Sakine, Samideh Khoei, Sepideh Khoee, Nida Jamali Raoufi, Mohammad Reza Karimi, and Ali Shakeri-Zadeh. "Development of a magnetic nano-graphene oxide Carrier for improved glioma-targeted drug delivery and imaging: In vitro and in vivo evaluations." Chemico-Biological Interactions (2018). https://www.sciencedirect.com/science/article/pii/S0009279718301601

“Abstract: To overcome the obstacles inflicted by the BBB in Glioblastoma multiforme (GBM) we investigated the use of Multifunctional nanoparticles that designed with a Nano-graphene oxide (NGO) sheet functionalized with magnetic poly (lactic-co-glycolic acid) (PLGA) and was used for glioma targeting delivery of radiosensitizing 5-iodo-2-deoxyuridine (IUdR). In vitro biocompatibility of nanocomposite has been studied by the MTT assay. In vivo efficacy of magnetic targeting on the amount and selectivity of magnetic nanoparticles accumulation in glioma-bearing rats under an external magnetic field (EMF) density of 0.5 T was easily monitored with MRI. IUdR-loaded magnetic NGO/PLGA with a diameter of 71.8 nm, a zeta potential of −33.07 ± 0.07 mV, and a drug loading content of 3.04 ± 0.46% presented superior superparamagnetic properties with a saturation magnetization (Ms) of 15.98 emu/g. Furthermore, Prussian blue staining showed effective magnetic targeting, leading to remarkably improved tumor inhibitory efficiency of IUdR. The tumor volume of rats after treatment with IUdR/NGO/SPION/PLGA + MF was decreased significantly compared to the rats treated with buffer saline, IUdR and SPION/IUdR/NGO/PLGA. Most importantly, our data demonstrate that IUdR/NGO/SPION/PLGA at the present magnetic field prolongs the median survival time of animals bearing gliomas (38 days, p < 0.01). Nanoparticles also had high thermal sensitivities under the alternating magnetic field. In conclusion, we developed magnetic IUdR/NGO/PLGA, which not only achieved to high accumulation at the targeted tumor site by magnetic targeting but also indicated significantly enhanced therapeutic efficiency and toxicity for glioma both in vitro and in vivo. This innovation increases the possibility of improving clinical efficiency of IUdR as a radiosensitizer, or lowering the total drug dose to decrease systemic toxicity. Graphical abstract: Schematic illustration of magnetic drug delivery, verified by staining and use as an MRI contrast agent with IUdR/GO/SPION/PLGA and MF. Highlights: IUdR-loaded magnetic NGO + MF indicated the strongest anticancer effects in rat gliomas. Magnetic NGO induces thermosensitising effects in alternative magnetic field. Magnetic NGO under external magnetic field could overcome the BBB. Magnetic NGO could enhance the MRI sensitivity. Magnetic NGO modified with PLGA showed sustained release of IUdR. Keywords: Superparamagnetic iron oxide Glioma Magnetic targeting 5-Iodo-2′-deoxyuridine Nano-graphene oxide”


You’re invited to the Biotech, Pharma, Cancer, Research (BPCR) Scientific Networking Meeting this Wednesday (8/29) at KPTC.

Monday, August 27, 2018, 11:04 AM ET




The first annual BPCR even will be held in the Kurz Purdue Technology Center from 9 AM to 4 PM as an opportunity to get out there, network, learn about companies in the area as well as meet with potential collaborators, customers, and investors. Event speakers include Anton Iliuk (Tymora), Rob Hill (Hatch 51), Kelvin Okamoto (Gen3Bio), Cedric D’Hue (D’Hue Law), Kyle Lutes (Delmar), Laura Downey (Concordance), Pete Kissinger (BASI), Ardian Wibowo (Helix) Joanne Zhane (Phytoption), Bill Ooms (BSS), and John Garner (Akina). The exhibit hall features 16 different companies including LyoHUB, Akanocure, PGC, Triclinic labs, BI, Purdue OTC, Zeblock, Miftek, and LSAI laboratories as well as several others. The event is free of charge and open to the public. See more at www.BPCRconference.com. We look forward to seeing you there.


PEG-PLGA from PolySciTech used in research on PEGylated long-circulating nanoparticles

Monday, August 20, 2018, 3:43 PM ET



One of the mechanisms for loss of nanoparticles from the blood-stream is removal by macrophages. This process is particularly pronounced in the liver, where particles are up-taken as part of hepatic clearance of ‘non-self’ components from the blood-stream. One means of preventing macrophage uptake is the addition of a pegylated shell to the outside of the nanoparticle as PEG reduces non-specific protein adsorption. Recently, researchers at Drexel University utilized mPEG-PLGA (PolyVivo AK037) from PolySciTech (www.polyscitech.com) to generate PEGylated nanoparticles and tested the particles under a variety of conditions to obtain a better understanding of how these particles can be modified to prevent clearance from the blood-stream. This research holds promise for the development of improved long-circulating nanoparticle drug-delivery systems. Read more: Zhou, Hao, Zhiyuan Fan, Peter Y. Li, Junjie Deng, Dimitrios C. Arhontoulis, Christopher Y. Li, Wilbur B. Bowne, and Hao Cheng. "Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial Cells for Long Blood Circulation." ACS nano (2018). https://pubs.acs.org/doi/abs/10.1021/acsnano.8b04947

“Research into long-circulating nanoparticles has in the past focused on reducing their clearance by macrophages. By engineering a hierarchical polyethylene glycol (PEG) structure on nanoparticle surfaces, we revealed an alternative mechanism to enhance nanoparticle blood circulation. The conjugation of a second PEG layer at a density close to, but lower than the mushroom-to-brush transition regime on conventional PEGylated nanoparticles dramatically prolongs their blood circulation via reduced nanoparticle uptake by non-Kupffer cells in the liver, especially liver sinusoidal endothelial cells (LSECs). Our study also disclosed that the dynamic outer PEG layer reduces protein binding affinity to nanoparticles, although not the total number of adsorbed proteins. These effects of the outer PEG layer diminishes in the higher density regime. Therefore, our results suggest that the dynamic topographical structure of nanoparticles is an important factor in governing their fate in vivo. Taken together, this study advances our understanding of nanoparticle blood circulation and provides a facile approach for generating long circulating nanoparticles.”

BPCR conference (August 29, 2018 9AM - 4PM: Kurz Purdue Technology Center, West Lafayette, IN) is a free, 1-day scientific-networking conference hosted by Akina, Inc. See more BPCRconference.com.


These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/ where you can post a question or comment. (Load took 0.5019109249115 seconds)

 

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