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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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PLGA and PLGA-PEG-Mal from PolySciTech used in development of cancer immunotherapy

Friday, December 15, 2017, 10:09 PM ET



One of the more insidious facets of cancer is that, for a variety of biochemical reasons, most cancers do not elicit an immune response from the body. The human body’s immune system is well adept at thwarting foreign cells and pathogens and is very capable of destroying many cancer cells once activated. For this reason, there has been a great deal of research in ‘immunotherapy’ which is effectively a process of vaccinating the human body against cancer so that it recognizes and destroys cancer cells as though they were pathogens. This provides for a much more selective therapy overall as compared to conventional cytotoxic chemotherapies. Recently, researchers at Dana Faber, Harvard Medical School, MIT, Howard Hughes Medical Institute, and Koch Institute for Integrative Cancer Research utilized Mal-PEG-PLGA (Cat# AI053) and PLGA (Cat # AP041) from PolySciTech (www.polyscitech.com) to generate nanoparticles with reactive exteriors. These nanoparticles were conjugated to targeting ligands via Michael’s reaction between the maleimide units and thiol-bearing antibody fragments. The formed nanoparticles were found to target immune cells and deliver immunotherapy agents to them. This research holds promise for enhanced cancer therapy. Read more: Cartwright, A.N., Hartl, C.A., Park, C.G., Schmid, D., Irvine, D.J., Freeman, G.J., Maiarana, J., Wucherpfennig, K.W., Goldberg, M.S., Subedi, N. and Puerto, R.B., 2017. T cell-targeting nanoparticles focus delivery of immunotherapy to improve antitumor immunity. Nature communications, 8, p.1747. https://www.nature.com/articles/s41467-017-01830-8


“Abstract: Targeted delivery of compounds to particular cell subsets can enhance therapeutic index by concentrating their action on the cells of interest. Because attempts to target tumors directly have yielded limited benefit, we instead target endogenous immune cell subsets in the circulation that can migrate actively into tumors. We describe antibody-targeted nanoparticles that bind to CD8+ T cells in the blood, lymphoid tissues, and tumors of mice. PD-1+ T cells are successfully targeted in the circulation and tumor. The delivery of an inhibitor of TGFβ signaling to PD-1-expressing cells extends the survival of tumor-bearing mice, whereas free drugs have no effect at such doses. This modular platform also enables PD-1-targeted delivery of a TLR7/8 agonist to the tumor microenvironment, increasing the proportion of tumor-infiltrating CD8+ T cells and sensitizing tumors to subsequent anti-PD-1. Targeted delivery of immunotherapy to defined subsets of endogenous leukocytes may be superior to administration of free drugs.”


PLGA-PEG-PLGA from PolySciTech used in development of infantile hemangioma treatment

Monday, December 11, 2017, 10:40 AM ET


Infantile hemangioma is a non-cancerous tumor in which an excess of blood vessels grow in a particular area with excessive cell proliferation. Small, skin hemangioma’s manifest as benign birthmarks and do not typically require treatment. However, large hemangioma’s or hemangioma’s that affect organs (especially the liver) can be fatal and require treatment. Since these affect primarily infants, treatment must be performed carefully as side-effects and other complications can be readily encountered due to size and metabolic features in very small children. Recently, researchers from Henan Provincial People’s Hospital and Second Military Medical University utilized PLGA-PEG-PLGA (Polyvivo#: AK016) from PolySciTech (www.polyscitech.com) to formulate urea-loaded microspheres as a delivery system to treat hemangioma. This research holds promise for treating this potentially life-threatening infantile disease. Read more: Zhu, Xiaoshuang, Xiaonan Guo, Dakan Liu, Yubin Gong, Jin Sun, and Changxian Dong. "Significant inhibition of infantile hemangioma growth by sustained delivery of urea from liposomes-in-microspheres." Oncology Reports 39, no. 1 (2018): 109-118. https://www.spandidos-publications.com/or/39/1/109

“Abstract: Infantile hemangioma (IH) is a benign pediatric tumor, and rapid growth of IH can result in serious morbidity and even mortality. Only one drug Hemangeol™ (propranolol hydrochloride oral solution) has been approved for the treatment of IH, whereas patients suffer from its adverse effects and high frequency of administration. We have used urea, an organic compound and a normal body metabolite, in the treatment of IH for 20 years, and demonstrated that urea is an effective and well-tolerated treatment for IH. To reduce the daily administration of urea, we firstly utilized urea-loaded liposomes-in-microspheres (ULIM) as a novel topical controlled release system to realize the sustained release of urea. ULIM were fabricated from the encapsulation of urea-loaded liposomes in poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) microspheres. The characteristics, activity and mechanism against IH of ULIM were examined in vitro and in vivo. ULIM were of a desired particle size (~62.4 µm), drug encapsulation efficiency (~51.5%) and sustained drug release for 40 days. ULIM inhibited the proliferation of hemangioma endothelia cells (HemECs) and expression of vascular endothelial growth factor-A in HemECs. The therapeutic effect of ULIM in IH was better than propranolol, urea, urea-loaded liposomes and urea-loaded microspheres in vivo, as reflected by markedly decreased hemangioma weight, volume and microvessel density. None of the treated mice showed behavioral changes, severe sideeffects and weight loss. Our results suggest that use of ULIM is a potential and safe approach with which to locally and efficiently deliver urea to hemangioma, and is a promising alternative to propranolol in the treatment of IH.”


PEG-PLGA from PolySciTech used in development of gastric cancer treatment

Friday, December 8, 2017, 10:19 PM ET



Gastric cancer is a very common and deadly form of cancer which kills about 11,000 people per year in America. Eliminating cancer stem cells is a key step to treating this form of cancer. Recently, researchers working at Sichuan University, Guizhuo Provincial People’s Hospital, and Second Military Medical University (China) utilized PEG-PLGA From PolySciTech (www.polyscitech.com) to develop nanoparticles loaded with salinomycin, which kills cancer stem-cells, and docetaxel, a standard chemotherapy agent, for treatment of gastric cancer. They found this combination in nanoparticles suppressed tumor growth more effectively than alone or without the nanoparticles. This research holds promise for treating this common and lethal form of cancer. Read more: Li, Lan, Dejun Cui, Limin Ye, Yu Li, Liyi Zhu, Lanqun Yang, Banjun Bai, Zhao Nie, Jie Gao, and Yu Cao. "Codelivery of salinomycin and docetaxel using poly (D, L-lactic-co-glycolic acid)-poly (ethylene glycol) nanoparticles to target both gastric cancer cells and cancer stem cells." Anti-Cancer Drugs 28, no. 9 (2017): 989-1001. http://journals.lww.com/anti-cancerdrugs/Fulltext/2017/10000/Codelivery_of_salinomycin_and_docetaxel_using.6.aspx

“Cancer stem cells (CSCs) in gastric cancer (GC) have been established recently as key therapeutic targets for the successful treatment of GC. Emerging evidence suggests that both CSCs and cancer cells should be eradicated to achieve optimal therapeutic efficacy. In the present study, salinomycin, which has been reported to kill CSCs, was used in combination with docetaxel, a chemotherapeutic drug that is used as first-line therapy in GC, to eradicate both GC stem cells (SCs) and cancer cells. Salinomycin and docetaxel were loaded separately into poly(D,L-lactic-co-glycolic acid)-poly(ethylene glycol) nanoparticles of 140 nm with a narrow size distribution, high drug loading, and sustained drug release. GC SCs were isolated by magnetic-activated cell sorting on the basis of CD44 expression as the CSC phenotype. CD44+ GC SCs showed the characteristics of CSCs, including increased SC gene expression, tumorsphere formation capacity, and tumorigenicity in nude mice. We found that both salinomycin and salinomycin-loaded nanoparticles (salinomycin-NPs) could selectively eradicate GC SCs, as reflected by reduced tumorsphere formation capacity and the frequency of CD44+ GC cells, whereas docetaxel and docetaxel-loaded nanoparticles (docetaxel-NPs) could significantly eradicate GC cells. In nude mice bearing GC xenografts, salinomycin-NPs and salinomycin significantly decreased the intratumor population of GC SCs. Notably, salinomycin-NPs combined with docetaxel-NPs suppressed tumor growth more effectively than did salinomycin combined with docetaxel, single salinomycin-NPs, or docetaxel-NPs. Therefore, salinomycin-NPs combined with docetaxel-NPs represent a promising strategy for the treatment of GC by eradicating both GC SCs and cancer cells.”


Maleimide-PEG-PLGA from PolySciTech used in development of nanoparticle system for treatment of arthritis

Friday, December 8, 2017, 10:18 PM ET



Arthritis is a debilitating inflammatory disease of the joints which can damage cartilage and create a considerable amount of pain as well as loss of function for the patient. Targeted therapy offers hope for relief to patients from this chronic disease. One means of generating targeted nanoparticles is to utilize thiol-maleimide reaction to connect peptides to the exterior of Maleimide-reacting nanoparticles made using Mal-PEG-PLGA. Recently, Researchers at University of Connecticut and University of Harford utilized mPEG-PLGA (PolyVivo #AK037) and Maleimide-PEG-PLGA (Polyvivo #AI020) from PolySciTech (www.polyscitech.com) to generate a nanoparticle system for treatment of arthritis. This research holds promise for treating this debilitating disease. Read more: Jiang, Tao, Ho-Man Kan, Komal Rajpura, Erica J. Carbone, Yingcui Li, and Kevin W-H. Lo. "Development of Targeted Nanoscale Drug Delivery System for Osteoarthritic Cartilage Tissue." Journal of Nanoscience and Nanotechnology 18, no. 4 (2018): 2310-2317. http://www.ingentaconnect.com/contentone/asp/jnn/2018/00000018/00000004/art00006

Osteoarthritis is a severe and debilitating joint disease, which is characterized as results from damage and degeneration of the articular cartilage of the joint surfaces. The incidence of osteoarthritis is growing increasingly high while current treatment methods remain suboptimal. The major issue for current osteoarthritic medications is that patients frequently experience adverse, nonspecific side effects that are not a direct result of the specific pharmacological action of the drug. The treatment processes could be made more effective, safe, and comfortable if it were possible to deliver the drugs specifically to cartilage tissue. Therefore, developing site-specific and controlled drug release delivery systems is needed for overcoming the aforementioned issues. We have developed a poly(lactic-co-glycolic acid) (PLGA)-based nanoscale drug delivery system based on a short cartilage-targeting peptide sequence: WYRGRL. Nanoparticles (NPs) made of methoxy-poly(ethylene glycol) (PEG)-PLGA and maleimide-PEG-PLGA were prepared using a water-in-oil-in-water double emulsion and solvent evaporation method. Fluorescein isothiocyanate (FITC)-tagged WYRGRL peptide was then linked to the surface of the nanoparticles through the alkylation reaction between the sulfhydryl groups at the N-terminal of the peptide and the C═C double bond of maleimide at one end of the polymer chain to form thioether bonds. The conjugation of FITC-tagged WYRGRL peptide to PLGA NPs was confirmed by NMR technique. We further demonstrated that the novel delivery system binds very specifically to cartilage tissue in vitro and ex vivo. Given that biodegradable PLGA-based NPs have shown promise for drug delivery, they could be used for a positive advancement for treatments of osteoarthritic patients by creating a more effective treatment process that achieves healing results faster and with fewer deleterious side effects. Taken together, these promising results indicated that this nanoscale targeting drug delivery system was able to bind to cartilage tissue and might have a great potential for treating osteoarthritis. Keywords: Musculoskeletal Tissue; Nanomedicine; Osteoarthritis; Targeted Drug Delivery; Targeting Ligands


PEG-PLGA from PolySciTech used in development of nanoparticle-based Leukemia treatment

Friday, December 8, 2017, 10:17 PM ET



Leukemia is a cancer which affects how blood cells are produced in bone marrow and contributes to about 24,500 deaths each year in US. T cell acute lymphoblastic leukemia (T-ALL), in particular is a form of leukemia which has poor survival prognosis in adult (<50 a="" affected="" and="" be="" bone-marrow="" both="" by="" can="" chemotherapeutics.="" effect.="" effectiveness="" for="" from="" have="" href="http://www.polyscitech.com/" huazhong="" improved="" inhibitors="" into="" its="" jiao="" kinase="" maximum="" nanoparticles="" of="" other="" peg-plga="" polyscitech="" preferentially="" purchased="" recently="" regions="" requires="" researchers="" science="" shanghai="" technology="" the="" these="" tissue="" to="" tong="" traditional="" treatment="" treatments="" university="" uptake="" using="">www.polyscitech.com
) to make nanoparticles co-loaded with both IRAK (kinase inhibitor) and ABT-737 (microtubule-targeting chemotherapeutic) for leukemia therapy. This research holds promise to improve therapeutic and survival outcomes for this difficult to treat disease. Read more: Wu, Xiaoyan, Lin Wang, Yining Qiu, Bingyu Zhang, Zhenhua Hu, and Runming Jin. "Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia." International Journal of Nanomedicine 12 (2017): 8025. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5673049/


“Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution. Keywords: T cell acute lymphoblastic leukemia, IRAK1/4 inhibitor, ABT-737, Box-Behnken design and response surface methodology, PEG-PLGA”


PEG-PLA from PolySciTech utilized in development of nanoparticles to protect kidneys during transplant procedures.

Tuesday, December 5, 2017, 8:12 PM ET



Kidney transplantation is a life-saving practice in which a donor kidney is transplanted into a recipient. During kidney transplantation, damage to the organ can occur when the flow of blood through it stops (upon removal from the donor) and suddenly restarts again once placed in the recipient. This incidence of ‘reperfusion injury’ can damage the delicate lining of the organ and potentially lead to a loss of function. Recently, researchers from Yale University and University of Cambridge utilized mPEG-PLA (PolyVivo AK054) from PolySciTech (www.polyscitech.com) to develop nanoparticles that coat and protect the interior of kidneys so that they are less affected by reperfusion injury. This research holds promise both to protect organs for transplant, as well as to treat any problems with the organ during the time between removal and placement. Read more: Tietjen, Gregory T., Sarah A. Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R. Kraehling et al. "Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys." Science Translational Medicine 9, no. 418 (2017): eaam6764. http://stm.sciencemag.org/content/9/418/eaam6764.abstract


“Abstract: Particle perfusion for organ transplant: Ischemia-reperfusion injury, which occurs when a tissue or organ is temporarily cut off from blood flow, is a major issue limiting organ viability for transplantation. Tietjan et al. devised a way to target the injury-sensitive endothelium of organs during ex vivo perfusion. Using nanoparticles conjugated to an antibody targeting a protein expressed on endothelial cells, the authors demonstrated that they could perfuse human kidneys and that nanoparticles accumulated in kidney endothelial cells. In addition to expanding the pool of viable organs for transplant, this approach could potentially be used to deliver targeted therapies to organs during ex vivo perfusion rather than treating the transplant recipient systemically. Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess and resuscitate organs likely to be declined for transplantation, thereby increasing the number of viable organs available. Short periods of NMP provide a window of opportunity to deliver therapeutics directly to the organ and, in particular, to the vascular endothelial cells (ECs) that constitute the first point of contact with the recipient’s immune system. ECs are the primary targets of both ischemia-reperfusion injury and damage from preformed antidonor antibodies, and reduction of perioperative EC injury could have long-term benefits by reducing the intensity of the host’s alloimmune response. Using NMP to administer therapeutics directly to the graft avoids many of the limitations associated with systemic drug delivery. We have previously shown that polymeric nanoparticles (NPs) can serve as depots for long-term drug release, but ensuring robust NP accumulation within a target cell type (graft ECs in this case) remains a fundamental challenge of nanomedicine. We show that surface conjugation of an anti-CD31 antibody enhances targeting of NPs to graft ECs of human kidneys undergoing NMP. Using a two-color quantitative microscopy approach, we demonstrate that targeting can enhance EC accumulation by about 5- to 10-fold or higher in discrete regions of the renal vasculature. In addition, our studies reveal that NPs can also nonspecifically accumulate within obstructed regions of the vasculature that are poorly perfused. These quantitative preclinical human studies demonstrate the therapeutic potential for targeted nanomedicines delivered during ex vivo NMP.”


Cell-scaffold interaction quantitatively investigated using fluorescently labeled PLGA from PolySciTech

Tuesday, December 5, 2017, 8:06 PM ET



A powerful technique commonly applied in tissue engineering is cell-scaffolding in which a highly-porous, biocompatible material is implanted into a patient. This mesh allows for cells to grow inside of its structure to repair damaged or lost tissue. There still remains a great deal to learn about exactly how cells interact with the substrate they are growing on, as the structure and chemistry of the mesh is critical to how the cells grow. One common problem with growing roughly translucent microscopic cells on an opaque microfiber mesh is visualizing what is going on with the cells. This is where fluorescent imaging comes in to play. In this method, each component is bound to a specific dye that emits light when excited by a specific wavelength of light. This allows researchers to image each component of the system, separately. Recently, researchers from National institute of Standards and Technology (NIST) and National Institute of Health (NIH) utilized fluorescently conjugated PLGA-FKR648 (PolyVivo AV015) from PolySciTech (www.polyscitech.com) to make a series of cell-scaffolds and test their interactions with cells. The fluorescent nature of this polymer allowed for direct imaging of the mesh by fluorescence techniques, so they could investigate cell-interactions in fine detail. This research provides a valuable tool for tissue-engineering researchers looking to optimize their mesh designs. Read more: Bajcsy, Peter, Soweon Yoon, Stephen J. Florczyk, Nathan A. Hotaling, Mylene Simon, Piotr M. Szczypinski, Nicholas J. Schaub, Carl G. Simon, Mary Brady, and Ram D. Sriram. "Modeling, validation and verification of three-dimensional cell-scaffold contacts from terabyte-sized images." BMC Bioinformatics 18, no. 1 (2017): 526. https://bmcbioinformatics.biomedcentral.com/articles/10.1186/s12859-017-1928-x


“Background: Cell-scaffold contact measurements are derived from pairs of co-registered volumetric fluorescent confocal laser scanning microscopy (CLSM) images (z-stacks) of stained cells and three types of scaffolds (i.e., spun coat, large microfiber, and medium microfiber). Our analysis of the acquired terabyte-sized collection is motivated by the need to understand the nature of the shape dimensionality (1D vs 2D vs 3D) of cell-scaffold interactions relevant to tissue engineers that grow cells on biomaterial scaffolds. Results: We designed five statistical and three geometrical contact models, and then down-selected them to one from each category using a validation approach based on physically orthogonal measurements to CLSM. The two selected models were applied to 414 z-stacks with three scaffold types and all contact results were visually verified. A planar geometrical model for the spun coat scaffold type was validated from atomic force microscopy images by computing surface roughness of 52.35 nm ±31.76 nm which was 2 to 8 times smaller than the CLSM resolution. A cylindrical model for fiber scaffolds was validated from multi-view 2D scanning electron microscopy (SEM) images. The fiber scaffold segmentation error was assessed by comparing fiber diameters from SEM and CLSM to be between 0.46% to 3.8% of the SEM reference values. For contact verification, we constructed a web-based visual verification system with 414 pairs of images with cells and their segmentation results, and with 4968 movies with animated cell, scaffold, and contact overlays. Based on visual verification by three experts, we report the accuracy of cell segmentation to be 96.4% with 94.3% precision, and the accuracy of cell-scaffold contact for a statistical model to be 62.6% with 76.7% precision and for a geometrical model to be 93.5% with 87.6% precision. Conclusions: The novelty of our approach lies in (1) representing cell-scaffold contact sites with statistical intensity and geometrical shape models, (2) designing a methodology for validating 3D geometrical contact models and (3) devising a mechanism for visual verification of hundreds of 3D measurements. The raw and processed data are publicly available from https://isg.nist.gov/deepzoomweb/data/ together with the web -based verification system. Keywords: Co-localization Cellular measurements Cell-scaffold contact Segmentation models Contact evaluation Web-based verification Large-volume 3D image processing”


PLGA melting temperature

Tuesday, December 5, 2017, 8:26 AM ET


Image shows DSC determined melting temperature of a series of PolyVivo PLGA's as well as LA:GA ratio and MW. For very low MW PLGA's, the melting temperature can even be at room temperature or below.



Thermogelling PLGA-PEG-PLGA from PolySciTech used in development of ocular RNA-nanoparticle delivery system

Tuesday, November 28, 2017, 10:20 PM ET



Delivering drugs to the human eye presents a unique set of challenges. Since the injection volume is extremely low and the surrounding tissue is extremely sensitive, care must be taken to use biocompatible carriers with high payload. One means to do this is to use nanoparticles while another is to use thermogelling polymers (ie polymers which transition from a liquid solution at room temperature to a solid gel at body temperature). A powerful delivery technique is to load nanoparticles inside of thermogelling polymers so as to control the release of the nanoparticles. Recently, Researchers at University of Cincinnati, Silpakorn University, Indiana University, and The Ohio State University used PLGA-PEG-PLGA (PolyVivo AK024, AK097) from PolySciTech (www.polyscitech.com) to entrap RNA-nanoparticles and track their distribution in the eye. This research holds promise for providing for more effective ocular drug-delivery. Read more: Shi, Zhanquan, S. Kevin Li, Ponwanit Charoenputtakun, Chia-Yang Liu, Daniel Jasinski, and Peixuan Guo. "RNA nanoparticle distribution and clearance in the eye after subconjunctival injection with and without thermosensitive hydrogels." Journal of Controlled Release (2017). https://www.sciencedirect.com/science/article/pii/S0168365917310246


“Abstract: Thermodynamically and chemically stable RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA from bacteriophage phi29 were examined previously for ocular delivery. It was reported that RNA nanoparticles with tri-way shape entered the corneal cells but not the retinal cells, whereas particle with four-way shape entered both corneal and retinal cells. The present study evaluated ocular delivery of RNA nanoparticles with various shapes and sizes, and assessed the effect of thermosensitive hydrogels (poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid); PLGA-PEG-PLGA) for increasing the retention of RNA nanoparticles in the eye. Fluorescence imaging of mouse eyes and fluorescence microscopy of dissected eye tissues from the conjunctiva, cornea, retina, and sclera were performed to determine the distribution and clearance of the nanoparticles in the eyes after subconjunctival injection in vivo. RNA nanoparticles entered the cells of the conjunctiva, cornea, retina, and sclera after subconjunctival delivery. The clearance of RNA pentagon was slower than both RNA square and triangle of the same designed edge length (10 nm) in the eye, and the clearance of RNA squares of the longer edge lengths (10 and 20 nm) was slower than RNA square of the shorter edge length (5 nm), this indicating that the size could affect ocular pharmacokinetics of the nanoparticles. At 24 h after the injection, approximately 6–10% of the fluorescence signal from the larger nanoparticles in the study (RNA square of 20 nm edge length and RNA pentagon of 10 nm edge length) remained in the eye, and up to 70% of the retinal cells contained the nanoparticles. The results suggest that the larger nanoparticles were “gulped” in conjunctival, corneal, retinal, and scleral cells, similar to the behavior observed in macrophages. Additionally, the combination of RNA nanoparticles with the thermosensitive polymers increased the retention of the nanoparticles in the eye. Keywords: RNA nanoparticle; Double-stranded RNA; Temperature sensitive polymer; Subconjunctival; Ocular delivery”


Thanksgiving

Wednesday, November 22, 2017, 3:36 PM ET



Akina, Inc. (www.akinainc.com) will be closed Thursday and Friday (11/23-11/24) for the Thanksgiving Holiday. Any orders placed during this time will be filled the following business day. Happy Thanksgiving.


PLA from PolySciTech used in development of nanoparticle-based triple-negative breast cancer therapy

Wednesday, November 15, 2017, 7:44 PM ET


Most forms of breast cancer respond well to conventional therapies, such as doxorubicin. There is, however, a specific type of breast cancer that is referred to as ‘triple-negative’ (named this because it does not have receptors for estrogen, progesterone, or HER2) breast cancer. It is highly resistant to conventional chemotherapy and very invasive. Recently, researchers at University of Cincinnati utilized polylactide (AP128) from PolySciTech (www.polyscitech.com) to develop chemotherapy particles which released gefitinib followed by sequential release of doxorubicin. These particles were found to be significantly more effective at treating triple-negative breast cancer than . This research holds promise for developing more effective chemotherapy strategies to treat breast cancer. Read more: Zhou, Zilan, Mina Jafari, Vishnu Sriram, Jinsoo Kim, Joo-Youp Lee, Sasha J. Ruiz-Torres, and Susan E. Waltz. "Delayed Sequential Co-Delivery of Gefitinib and Doxorubicin for Targeted Combination Chemotherapy." Molecular Pharmaceutics (2017). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.7b00669

“There are an increasing number of studies showing the order of drug presentation plays a critical role in achieving optimal combination therapy. Here, a nanoparticle design is presented using ion pairing and drug-polymer conjugate for the sequential delivery of gefitinib (Gi) and doxorubicin (Dox) targeting epidermal growth factor receptor (EGFR) signaling applicable for the treatment of triple negative breast cancers. To realize this nanoparticle design, Gi complexed with dioleoyl phosphatidic acid (DOPA) via ion paring was loaded onto the nanoparticle made of Dox-conjugated poly(l-lactide)-block-polyethylene glycol (PLA-b-PEG) and with an encapsulation efficiency of ∼90%. The nanoparticle system exhibited a desired sequential release of Gi followed by Dox, as verified through release and cellular uptake studies. The nanoparticle system demonstrated approximate 4-fold and 3-fold increases in anticancer efficacy compared to a control group of Dox–PLA-PEG conjugate against MDA-MB-468 and A549 cell lines in terms of half maximal inhibitory concentration (IC50), respectively. High tumor accumulation of the nanoparticle system was also substantiated for potential in vivo applicability by noninvasive fluorescent imaging. Keywords: combination therapy; controlled delivery; doxorubicin; EGFR inhibitor; nanoparticles; sequential delivery”


PLGA and PLGA-rhodamine from PolySciTech used in study on chemotherapeutic delivery by nanoparticles

Wednesday, November 15, 2017, 7:41 PM ET


For conventional, loose-drug, chemotherapy, less than 1% of the injected medicine actually makes it to the tumor site. The clinical method for solving this problem has been to inject massive doses of chemotherapeutic agents to the patient, in the hopes that at least some of the medicine makes it to the tumor. This is not a good solution to this problem and leads to substantial morbidity from the side-effects of chemotherapy (hair loss, immune-system damage, etc.). Nanoparticle-based technologies have been developed in the hopes of creating a system in which the drug is encapsulated in a small particle that flows through the blood until it is entrapped by the tumor. Although coating the particle with PEG improves its circulation time, it can also hinder uptake by the tumor. Recently, researchers from Purdue University and Eli Lilly and Company used PLGA (PolyVivo AP020) and Rhodamine-labelled PLGA (Polyvivo AV011) from PolySciTech (www.polyscitech.com) to develop chitosan-coated nanoparticles with preferential tumor attraction over PEGylated nanoparticles. They found, however, that although the particles were preferentially absorbed by the polymer, the drug itself (in the study, ICG tracer-dye was used) leached out too quickly to be of any use. This highlights how critical the drug-entrapment strategy is to the overall design of a nanoparticle formulation. This research holds promise to provide for improved chemotherapeutic strategies with reduced side-effects. Read more: Park, Jinho, Yihua Pei, Hyesun Hyun, Mark A. Castanares, David S. Collins, and Yoon Yeo. "Small molecule delivery to solid tumors with chitosan-coated PLGA particles: A lesson learned from comparative imaging." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309367

“Abstract: For polymeric nanoparticles (NPs) to deliver more drugs to tumors than free drug solution, it is critical that the NPs establish interactions with tumor cells and avoid removal from the tumors. Since traditional polyethylene glycol (PEG) surface layer interferes with the cell-NP interaction in tumors, we used a water-soluble and blood-compatible chitosan derivative called zwitterionic chitosan (ZWC) as an alternative surface coating for poly(lactic-co-glycolic acid) (PLGA) NPs. The ZWC-coated PLGA NPs showed pH-dependent surface charge profiles and differential cellular interactions according to the pH of the medium. The in vivo delivery of ZWC-coated NPs was evaluated in mice bearing LS174T-xenografts using magnetic resonance (MR) imaging and fluorescence whole body imaging, which respectively tracked iron oxide particles and indocyanine green (ICG) encapsulated in the NPs as tracers. MR imaging showed that ZWC-coated NPs were more persistent in tumors than PEG-coated NPs, in agreement with the in vitro results. However, the fluorescence imaging indicated that the increased NP retention in tumors by the ZWC coating did not significantly affect the ICG distribution in tumors due to the rapid release of the dye. This study shows that stable drug retention in NPs during circulation is a critical prerequisite to successful translation of the potential benefits of surface-engineered NPs. Keywords: pH-responsive Drug delivery PLGA nanoparticles Small molecules In vivo imaging Encapsulation stability”


PLGA-PEG-NHS from PolySciTech used as part of nanoparticle-protected-islets based treatment of diabetes

Thursday, November 9, 2017, 4:52 PM ET



Type 1 Diabetes is a chronic disease brought on by loss of function of pancreatic islets, groups of cells that produce insulin to regulate the blood sugar content. Recently, transplantation of pancreatic islets has been considered as a long-term treatment for type 1 diabetes that does not require the patient to take daily injections of insulin. Immune-system rejection of the transplant, however, creates difficult for this treatment method as the body attacks the newly transplanted cells. One means of preventing this is to encapsulate the cells in a material which is non-immunogenic so as to protect them from macrophages. Recently, researchers at Yeungnam University, Seoul National University, and Keimyung University (Korea) utilized PolyVivo AI111 (PLGA-PEG-NHS) from PolySciTech (www.polyscitech.com) to create pegylated nanoparticles which attach to the islet cells and prevent them from being attacked by the immune system. This research holds promise to provide for a long-term treatment of diabetes which does not require the patient to continuously inject insulin. Read more: Pham, Tung Thanh, Tiep Tien Nguyen, Shiva Pathak, Shobha Regmi, Hanh Thuy Nguyen, Tuan Hiep Tran, Chul Soon Yong et al. "Tissue adhesive FK506–loaded polymeric nanoparticles for multi–layered nano–shielding of pancreatic islets to enhance xenograft survival in a diabetic mouse model." Biomaterials (2017). http://www.sciencedirect.com/science/article/pii/S014296121730707X

“Abstract: This study aims to develop a novel surface modification technology to prolong the survival time of pancreatic islets in a xenogenic transplantation model, using 3,4–dihydroxyl–l–phenylalanine (DOPA) conjugated poly(lactide–co–glycolide)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (DOPA–NPs) carrying immunosuppressant FK506 (FK506/DOPA–NPs). The functionalized DOPA–NPs formed a versatile coating layer for antigen camouflage without interfering the viability and functionality of islets. The coating layer effectively preserved the morphology and viability of islets in a co–culture condition with xenogenic lymphocytes for 7 days. Interestingly, the mean survival time of islets coated with FK506/DOPA–NPs was significantly higher as compared with that of islets coated with DOPA–NPs (without FK506) and control. This study demonstrated that the combination of surface camouflage and localized low dose of immunosuppressant could be an effective approach in prolonging the survival of transplanted islets. This newly developed platform might be useful for immobilizing various types of small molecules on therapeutic cells and biomaterial surface to improve the therapeutic efficacy in cell therapy and regenerative medicine. Keywords: Surface modification; FK506; Islets transplantation; Local delivery; Diabetes mellitus”


PLGA-PEG-PLGA from PolySciTech used for localized propranolol delivery system

Wednesday, November 1, 2017, 9:12 PM ET



Hemangioma (red or purple colored birthmarks) is a benign childhood tumor generated by excessive growth of blood vessels. Although external hemangioma’s typically only affect aesthetics, the growth of internal hemangiomas, especially near liver, brain, or other critical organs, can cause severe pain and morbidity. Treatment options include corticosteroids and beta-blockers, however applying such treatments to infants and children throughout the whole body in a systemic fashion can create problems with controlling the dose and side-effects. Recently, researchers at Henan Provincial People’s Hospital and the Second Military Medical University (China) used PLGA-PEG-PLGA (PolyVivo AK016) from PolySciTech (www.polyscitech.com) to generate microparticles as part of a local propranolol delivery system. These particles were found to be effective at delivering propranolol (a beta blocker) locally without requiring a large systemic dose. This research holds promise for treating a variety of conditions where excessive angiogenesis is a problem. Read more: Guo, Xiaonan, Xiaoshuang Zhu, Dakan Liu, Yubin Gong, Jing Sun, and Changxian Dong. "Continuous delivery of propranolol from liposomes-in-microspheres significantly inhibits infantile hemangioma growth." International Journal of Nanomedicine 12 (2017): 6923. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609781/


“Purpose: To reduce the adverse effects and high frequency of administration of propranolol to treat infantile hemangioma, we first utilized propranolol-loaded liposomes-in-microsphere (PLIM) as a novel topical release system to realize sustained release of propranolol. Methods: PLIM was developed from encapsulating propranolol-loaded liposomes (PLs) in microspheres made of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) copolymers (PLGA-PEG-PLGA). The release profile of propranolol from PLIM was evaluated, and its biological activity was investigated in vitro using proliferation assays on hemangioma stem cells (HemSCs). Tumor inhibition was studied in nude mice bearing human subcutaneous infantile hemangioma. Results: The microspheres were of desired particle size (~77.8 μm) and drug encapsulation efficiency (~23.9%) and achieved sustained drug release for 40 days. PLIM exerted efficient inhibition of the proliferation of HemSCs and significantly reduced the expression of two angiogenesis factors (vascular endothelial growth factor-A [VEGF-A] and basic fibroblast growth factor [bFGF]) in HemSCs. Notably, the therapeutic effect of PLIM in hemangioma was superior to that of propranolol and PL in vivo, as reflected by significantly reduced hemangioma volume, weight, and microvessel density. The mean hemangioma weight of the PLIM-treated group was significantly lower than that of other groups (saline =0.28 g, propranolol =0.21 g, PL =0.13 g, PLIM =0.03 g; PLIM vs saline: P<0 .001="" a="" and="" approach="" conclusion:="" controlled="" deliver="" density="" efficiently="" findings="" group="" groups="" hemangioma.="" hemangioma="" infantile="" inhibition="" is="" keywords:="" leading="" liposomes="" locally="" lower="" mean="" microsphere="" microvessel="" mm2="" o:p="" of="" other="" our="" p="" pl:="" pl="25" plim-treated="" plim="" promising="" propranolol:="" propranolol="" release="" saline:="" saline="40" show="" significant="" significantly="" site="" than="" that="" the="" to="" very="" vessels="" vs="" was="">


PLGA-Glucose from PolySciTech used in cancer glucose-targeting nanoparticle development for cancer therapy

Tuesday, October 31, 2017, 9:18 PM ET


Cancer cells are typically be considered to act ‘hungry,’ as they consume glucose and oxygen at much faster rates than normal cells. For this, they have over-expressed glucose uptake moieties to absorb more of this energy filled sugar. This provides one method of targeting cancer which is to focus on their over-uptake of glucose as a targeting strategy. Recently, researchers at Seoul National University and Kangwon National University (Korea) utilized PLGA and PLGA-glucose from PolySciTech (www.polyscitech.com) (PolyVivo AP027 (PLGA-glucose) and AP041 (PLGA)) to create nanoparticles which target to the glucose uptake transporters of cancer cells. This research holds promise for improved cancer treatments by targeted delivery. Read more: Park, Ju-Hwan, Hyun-Jong Cho, and Dae-Duk Kim. "Poly ((D, L) lactic-glycolic) acid–star glucose nanoparticles for glucose transporter and hypoglycemia-mediated tumor targeting." International Journal of Nanomedicine 12 (2017): 7453. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5644567/


“Poly((D,L)lactic-glycolic)acid–star glucose (PLGA-Glc) polymer-based nanoparticles (NPs) were fabricated for tumor-targeted delivery of docetaxel (DCT). NPs with an approximate mean diameter of 241 nm, narrow size distribution, negative zeta potential, and spherical shape were prepared. A sustained drug release pattern from the developed NPs was observed for 13 days. Moreover, drug release from PLGA-Glc NPs at acidic pH (endocytic compartments and tumor regions) was significantly improved compared with that observed at physiological pH (normal tissues and organs). DCT-loaded PLGA-Glc NPs (DCT/PLGA-Glc NPs) exhibited an enhanced antiproliferation efficiency rather than DCT-loaded PLGA NPs (DCT/PLGA NPs) in Hep-2 cells, which can be regarded as glucose transporters (GLUTs)-positive cells, at ≥50 ng/mL DCT concentration range. Under glucose-deprived (hypoglycemic) conditions, the cellular uptake efficiency of the PLGA-Glc NPs was higher in Hep-2 cells compared to that observed in PLGA NPs. Cy5.5-loaded NPs were prepared and injected into a Hep-2 tumor-xenografted mouse model for in vivo near-infrared fluorescence imaging. The PLGA-Glc NPs group exhibited higher fluorescence intensity in the tumor region than the PLGA NPs group. These results imply that the PLGA-Glc NPs have active tumor targeting abilities based on interactions with GLUTs and the hypoglycemic conditions in the tumor region. Therefore, the developed PLGA-Glc NPs may represent a promising tumor-targeted delivery system for anticancer drugs. Keywords: PLGA-Glc, nanoparticles, glucose transporter, hypoxia, tumor targeting”


PLGA and PLCL from PolySciTech used in development of biodegradable foam for advanced wound treatment

Tuesday, October 24, 2017, 6:49 PM ET



One means to encourage wound healing, in either chronic or traumatic wounds, is to reduce the pressure across the wound surface to encourage local blood-flow, stimulate healing, and draw out excess fluids. This requires placing a sterile foam over the top of the wound and connecting the foam to a vacuum pump with an air-tight cover to apply vacuum to the wound. Conventionally, this is done with a non-degradable polyurethane-type foam. During this treatment, tissue often grows into the foam, which creates significant problems upon changing the dressing as fresh-grown tissue can be damaged. Recently, researchers at Wake Forest University utilized multiple PLGA, PLCL, and PCL products (PolyVivo AP037, AP081, AP036, AP073, AP013, and AP015) from PolySciTech (www.polyscitech.com) to develop a degradable, compressible foam for wound therapy. This research holds promise for development of improved wound-therapy methods using foams that simply resorb into the body rather than have problems with in-growth. Read more: Warner, Harleigh J., and William D. Wagner. "Fabrication of biodegradable foams for deep tissue negative pressure treatments." Journal of Biomedical Materials Research Part B: Applied Biomaterials. http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.34007/full

“ABSTRACT: Devices for negative pressure wound therapy (NPWT) rely on compressible foams operating at the tissue-device interface. Clinically used foams are nonabsorbable and if used on deep wounds or left in place for an extended period of time, excessive cell ingrowth and formation of granulation tissue into the foam may require a surgical procedure to remove the foam. Foams with fast degradation and with low immunogenicity and fibrotic response are required. Foams composed of combinations of poly(lactide-co-glycolide) (PLGA), poly(lactide-co-caprolactone) (PLCL), and polycaprolactone (PCL) were created by combined salt leaching and solvent displacement protocols. In vitro and in vivo degradation studies and mechanical properties of foams were evaluated and compared to clinically used poly(vinyl alcohol) (PVA) foam and PCL foams. Foams composed of PLGA (50:50 lactide:glycolide) of low molecular weight blended with PCL maintained mechanical properties and degraded significantly after 21 days of subcutaneous implantation in rats. The most ideal formulations for use in NPWT were identified as copolymeric PLGA (Mn 3000 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at either a 75:25 or 50:50 ratio, and copolymeric PLGA (Mn 7500 Da) at a lactide:glycolide ratio of 50:50 combined with PCL at a 50:50 ratio. KeyWords: polyester, polycaprolactone, poly(lactic-co-glycolic acid), foams, negative pressure wound therapy”


PLGA-PEG-PLGA thermogel from PolySciTech used in development of delivery system for ovarian cancer treatment

Monday, October 23, 2017, 9:08 PM ET



Ovarian cancer is particularly difficult to treat in a clinical setting as it has relatively few symptoms before progressing to an advanced stage. Chemotherapeutic agents tend to work well initially, but the cancer can become resistant quickly. One means to counter this is to apply drugs through the intraperitoneal route, a direct injection into the abdominal cavity. This allows for maximum exposure of the cancer to the chemotherapeutics. This, however, requires a thermogel delivery system which can trap the drug and allow for slow, controlled release of the compounds after the injection. Recently, researchers at University of Wisconsin-Madison and Mokpo National University (Korea), purchased PLGA-PEG-PLGA (PolyVivo AK012) from PolySciTech (www.polyscitech.com). They utilized this polymer to generate a thermogel and deliver chemotherapeutic agents epothilone B (EpoB), rapamycin, and tanespimycin. They found good pre-clinical results in reducing the growth of ovarian cancer cells by delivering these agents. This research holds promise for improved ovarian cancer treatment options. Read more: Shin, Dae Hwan, and Glen S. Kwon. "Pre-clinical evaluation of a themosensitive gel containing epothilone B and mTOR/Hsp90 targeted agents in an ovarian tumor model." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917309069


“Abstract: Despite clinical remission of epithelial ovarian cancer (EOC) after surgical resection and first-line chemotherapy, about 60% of patients will re-develop peritoneal metastasis and about 50% will relapse with chemoresistant disease. Clinical studies suggest that intra-peritoneal (i.p.) chemotherapy effectively treats residual EOC after cyto-reduction by gaining direct access into the peritoneal cavity, enabling elevated drug levels versus intravenous (i.v.) injection. However, chemoresistant disease is still problematic. To overcome resistance against microtubule stabilizing agents such as taxanes, epothilone B (EpoB) has merit, especially in combination with molecular targeted agents that inhibit heat shock protein 90 (Hsp90) and/or mammalian target of rapamycin (mTOR). In this paper, we report on the successful loading and solubilization of EpoB in a poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(d,l-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) thermosensitive gel (g-E). Further, we report on successful co-loading of 17-AAG (Hsp90) and rapamycin (mTOR) (g-EAR). After i.p. injection in mice, g-EAR showed gelation in the peritoneum and sustained, local-regional release of EpoB, 17-AAG, and rapamycin. In a luciferase-expressing ES-2 (ES-2-luc) ovarian cancer xenograft model, single i.p. injections of g-E and g-EAR delayed bioluminescence from metastasizing ES-2-luc cells for 2 and 3 weeks, respectively, despite fast drug release for g-EAR in vivo versus in vitro. In summary, a PLGA-b-PEG-b-PLGA sol-gel has loading and release capacities for EpoB and its combinations with 17-AAG and rapamycin, enabling a platform for i.p. delivery, sustained multi-drug exposure, and potent antitumor efficacy in an ES-2-luc, ovarian cancer i.p. xenograft model. Keywords: Drug combination; Epothilone B; Intraperitoneal injection; Ovarian cancer; Peritoneal carcinomatosis; Thermogel”


PLGA-cholesterol from PolySciTech used in development of bone-targeting nanoparticles as treatment for bone-marrow diseases

Friday, October 20, 2017, 9:20 PM ET


Delivery of medicinal molecules to bone tissue is very difficult as bone tissue is dense and poorly vascularized. Diseases of bone-marrow are particularly difficult to treat and can lead to death if they progress into leukemia. Recently, researchers working at Houston Methodist Research Institute, Weill Cornell Medical College, Harbin Medical University, and Huazhong University of Science and Technology (China) used cholesterol-endcapped from PolySciTech (www.polyscitech.com) (PolyVivo AP097) to develop a bone-targeting nanoparticle loaded with decitabine and arsenic trioxide, medicines which are effective at treating bone-marrow disorders. This particle was found to have preferential uptake into bone tissue and restored blood counts in a mouse model. This research holds promise for improved treatments for leukemia and other bone-marrow related diseases. Read more: Wu, Xiaoyan, Zhenhua Hu, Sara Nizzero, Guodong Zhang, R. Maricela Ramirez, Ce Shi, Jin Zhou, Mauro Ferrari, and Haifa Shen. "Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for effective therapy of myelodysplastic syndrome with low systemic toxicity." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S016836591730901X


“Abstract: Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and clonal hematopoietic stem cell disorders characterized by abnormal blood cells, or reduced peripheral blood cell count. Recent clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy on MDS treatment, but the treatment can cause significant side effects to patients. In addition, both drugs have to be administered on a daily basis due to their short half-lives. In addressing key issues of reducing toxic side effects and improving pharmacokinetic profiles of the therapeutic agents, we have developed a new formulation by co-packaging DAC and ATO into alendronate-conjugated bone-targeting nanoparticles (BTNPs). Our pharmacokinetic studies revealed that intravenously administered BTNPs increased circulation time up to 3 days. Biodistribution analysis showed that the BTNP facilitated DAC and ATO accumulation in the bone, which is 6.7 and 7.9 times more than untargeted NP. Finally, MDS mouse model treated with BTNPs showed better restoration of complete blood count to normal level, and significantly longer median survival as compared to free drugs or untargeted NPs treatment. Our results support bone-targeted co-delivery of DAC and ATO for effective treatment of MDS. Keywords: Myelodysplastic syndrome; Bone marrow; Delivery; Nanoparticle; Decitabine; Arsenic trioxide”


PLGA-PEG-NHS from PolySciTech used to generate peptide-functionalized nanoparticles in development of breast-cancer therapy

Wednesday, October 18, 2017, 4:12 PM ET


One of the requirements for cancer growth is increased blood-flow to the region where cancer affects the body. Most cancers induce angiogenesis, an excessive increase in the growth of blood-vessels in the region immediately surrounding the cancer, as a means to support their excessive growth. One strategy to eliminate cancer is to prevent angiogenesis, thus cutting off cancer from its supply of nutrients and oxygen which starves the tumor to death. There are several agents which can do this, but it is critical to control the exact targeting as prevention of growth of blood-vessels throughout the rest of the body can lead to toxic side-effects. Recently, researchers from AsclepiX Therapeutics and Johns Hopkins University utilized PLGA-PEG-NHS from PolySciTech (www.polyscitech.com) (PolyVivo AI111) to create nanoparticles with a biomimetic targeting moiety to improve nanoparticle targeting and tumor uptake for improved delivery of a novel anti-angiogenic peptide. These particles were found to preferentially bind to cancer, even to aggressive triple-negative breast cancer, and reduce available blood-flow to these tumors in an animal model. This research holds promise to provide for improved therapy of breast cancer. Read more: Kim, Jayoung, Eric Bressler, Ron Shmueli, Adam Mirando, Niranjan Pandey, Aleksander S. Popel, and Jordan J. Green. Biomaterials.org "Biodegradable polymeric nanoparticles targeted by a novel biomimetic peptide to human breast cancer." http://2017.biomaterials.org/sites/default/files/abstracts/0797.pdf

“Progression of tumor requires angiogenesis in order to achieve the increased need for oxygen and nutrients. Anti-angiogenesis is a widely investigated approach to prevent tumor growth (Bhise NS.Expert Opin Drug Deliv 2011; 8(4): 485-504). We have discovered a biomimetic peptide that shows potent anti-angiogenic activity in vitro and in vivo (Karagiannis ED.PNAS 2008; 105(37): 13775-13780). Nanoparticle (NP) formulations can be used for efficient systemic delivery and controlled release of such peptides at the target site to significantly enhance bioavailability while minimizing side effects. However, unmodified or poly(ethyleneglycol) (PEG)-coated polymeric NPs can suffer from a high rate of clearance and a low level of tumor accumulation (Wilhelm S. Nat. Rev. Mater. 2016; 1: 1-12). To overcome these limitations, we have designed a targeted poly(lactic-co-glycolic acid) (PLGA) NP with a biomimetic peptide as a novel targeting agent. In this study, we test PLGA NPs coated and loaded with peptide for the dual functionality of actively targeting human breast cancer and inducing anti-angiogenesis.”


Meet Akina, Inc at Purdue Research Park Vendor Fair Oct 18th

Monday, October 16, 2017, 1:35 PM ET


Akina, Inc. (www.akinainc.com) will be hosting a booth at the Purdue Research Park Vendor Fair is at Kurz Purdue Technology Center October 18th from 11AM-1PM. We will be answering questions about the company and our offerings as well as handing out 3DCellMaker T-shirts (while supplies last). Please join us for this event.



PLGA from PolySciTech used in development of novel micro-manufacturing technique for drug-delivery applications

Tuesday, October 10, 2017, 9:23 PM ET



Conventional emulsion-based methods can be used to create microparticles for drug delivery applications, however these have some drawbacks. There is little control over the distribution, structure, and spatial orientation of the particles and generally the formed particles are always spherical or nearly so. Most manufacturing techniques, such as 3D printing, lack the resolution capabilities to make micro-structured components. Recently, researchers at the Massachusetts Institute of Technology (MIT) utilized PLGA (PolyVivo AP045) from PolySciTech (www.polyscitech.com) to create a series of uniquely manufactured microstructures using a novel manufacturing technique. In this technique, the PLGA is heated and carefully pressed against a micropatterned mold to form the structure. Subsequent pressings can be applied to create more complex structures in micron dimensions. This research holds promise to generate new avenues for drug delivery by creating microparticles and structures which have precisely controlled time-release properties or functions based on shape and orientation. Read more: McHugh, Kevin J., Thanh D. Nguyen, Allison R. Linehan, David Yang, Adam M. Behrens, Sviatlana Rose, Zachary L. Tochka et al. "Fabrication of fillable microparticles and other complex 3D microstructures." Science 357, no. 6356 (2017): 1138-1142. http://science.sciencemag.org/content/357/6356/1138.abstract

“Abstract: Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing. SEAL allows us to generate microstructures with complex geometry at high resolution, produce fully enclosed internal cavities containing a solid or liquid, and use potentially any thermoplastic material without processing additives. Putting the pieces together: One route to improving the delivery of existing drugs is by encapsulation inside a protective but slowly degrading shell. Such slow-release capsules improve drug availability in vivo, reduce side effects, and allow for more constant dose delivery. McHugh et al. leverage a number of existing fabrication techniques to make tiny (400-µm), hollow injectable microparticles that can be filled with fluid containing the therapeutic agent. By adjusting the degradation rate of the microparticle material (in this case, a lactic/glycolic copolymer), the cargo in the internal reservoir can be released at a desired time, ranging from a few days to 2 months.”


PLGA-PEG-COOH from PolySciTech used in development of nanoparticle targeted delivery system

Monday, October 9, 2017, 10:53 AM ET



Most medicine applied today has no specific targeting system. Both most oral formulations and free-drug injections simply flood the entire blood-stream with a medicinal molecule such that the area of action receives enough dose to be therapeutic. This can be problematic in the situation of side-effects. Use of a delivery system, however, can ensure localization of the drug to a specific area. Recently, researchers utilized PLGA-PEG-COOH (PolyVivo AI034) from PolySciTech (www.polyscitech.com) to generate nanoparticles for targeted delivery of propranolol. Typically, propranolol is used to treat high blood pressure in a systemic application. However, with targeted application, it can be applied for treating hemangioma. This research holds promise to find new applications for existing medicines through targeted delivery. Read more: Guo, Xiaonan, Xiaoshuang Zhu, Jie Gao, Dakan Liu, Changxian Dong, and Xing Jin. "PLGA nanoparticles with CD133 aptamers for targeted delivery and sustained release of propranolol to hemangioma." Future Medicine (2017). https://www.futuremedicine.com/doi/abs/10.2217/nnm-2017-0130

“Aim: To develop propranolol-loaded poly(lactic-co-glycolic acid) nanoparticle with CD133 aptamers (PPN-CD133) to treat infantile hemangioma. Materials & methods: The antihemangioma activity and mechanism of PPN-CD133 were evaluated. Results & conclusion: PPN-CD133 are of desired size (143.7 nm), drug encapsulation efficiency (51.8%) and sustained drug release for 8 days. PPN-CD133 could effectively bind to CD133+ hemangioma stem cells, resulting in enhanced cytotoxic effect and reduced expression of angiogenesis factors in hemangioma stem cells. The therapeutic effect of PPN-CD133 in hemangioma was superior to that of untargeted PPN and propranolol in vivo, as reflected by reduced hemangioma volume, weight and microvessel density. PPN-CD133 represents a very promising approach to locally and efficiently deliver propranolol leading to significant inhibition of infantile hemangioma. Keywords: aptamer, biomaterials, cell biology, controlled release, nanoparticles, remove.”


Akina Happenings: Office of Generic Drugs Public Workshop presentation, shipping improvements.

Thursday, October 5, 2017, 2:51 PM ET


hese are busy times at PolySciTech division of Akina, Inc (www.polyscitech.com). Tomorrow, several employees will be at the FDA public workshop “Demonstrating Equivalence of Generic Complex Drug Substances and Formulations” October 6, 2017 (8:00 a.m. – 4:00 p.m.), FDA White Oak Campus (https://www.fda.gov/Drugs/NewsEvents/ucm552461.htm) with both a presentation by Dr. Kinam Park as well as three scientific poster presentations detailing research from collaborative work between the FDA and Akina, Inc. for development of a variety of assay techniques and methodologies. Also, Akina, Inc. is upgrading the packaging process for biodegradable polymers. In order to improve shipping condition, our products are now argon-flushed as part of the packaging process. Flushing the bottle with this chemically inert gas provides for an added layer protection during transport, by removing components that the polymer could potentially react with such as water and oxygen. This is in addition to the other precautions already taken (ice packs, desiccant) as part of shipping to ensure high product quality upon arrival.


PLA from PolySciTech used as part of polylysine based pancreatic cancer therapy development

Monday, September 25, 2017, 9:37 PM ET



Pancreatic cancer is a form of cancer which is very difficult to treat and can often be fatal. Peptides, such as polylysine, have been found to slow the growth of cancer however delivering them to the cancer site is difficult. Recently, researchers working at Universidad Nacional de Mar del Plata, Universidad Nacional de Cordoba (Argentina) University of Nebraska-Lincoln, and University of Sao Paulo (Brazil), utilized PLA (Polyvivo # AP078) from PolySciTech (www.polyscitech.com) as part of a microparticle system for delivery of polylysine as a treatment of pancreatic cancer. This research holds promise for providing treatment options for this fatal disease. Read more: Merari T. Chevalier, Mónica C. García, Daniela Gonzalez, Sandro M. Gomes-Filho, Daniela S. Bassères, Hernan Farina & Vera A. Alvarez (2017): Preparation, characterization and in vitro evaluation of ε-polylysine-loaded polymer blend microparticles for potential pancreatic cancer therapy, Journal of Microencapsulation, DOI: 10.1080/02652048.2017.1370028 (http://dx.doi.org/10.1080/02652048.2017.1370028)


“Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits the proliferation of several tumour lines in vitro and in vivo. However, proteins and peptide drugs possess certain disadvantages such as in vivo instability and short biological half-life. On the grounds that drug delivery systems can overcome a wide spectrum of bioactive compounds issues, a biopolymeric blend-based microparticulated system capable of delivering ε-polylysine (PLL) was developed. PLL-loaded poly((L)Lactic acid)/poly(D,L-Lactide)-co-poly(ethylene glycol)-based microparticles (PLL-PB-MPs) were prepared and fully characterised exhibiting a narrow size distribution (1.2 ± 0.12 µm), high loading efficiency (81%) and improved thermal stability (Td from 250 °C to 291 °C). The cytotoxicity and antiproliferative effect of PLL-PB-MPs in pancreatic adenocarcinoma cell lines BxPC3 and MIA PaCa-2 were confirmed. Due to their physicochemical and biopharmaceutical properties, PB-MPs constitute a promising carrier to deliver bioactive peptides. Keywords: Biopolymers, ε-polylysine, microparticles, polylactic acid”


PLGA-PEG-Mal from PolySciTech used in the development of Fn14-targeting nanoparticle system for brain cancer treatment

Monday, September 11, 2017, 1:21 PM ET



Glioblastoma accounts for 12-15% of all intracranial (brain) tumors. This particular form of brain-cancer is resistant to conventional therapies and tends to be rapidly growing, which makes this form of cancer particularly difficult to treat. Recently, researchers at the University of Maryland used mPEG-PLGA (PolyVivo# AK010) PLGA-PEG-Maleimide (PolyVivo# AI053), and PLGA-Rhodamine B (PolyVivo# AV011) from PolySciTech (www.polyscitech.com) to develop nanoparticles which bind strongly to the Fn14 receptor that is found in brain-cancer. This research holds promise to provide for additional treatment options to this deadly disease. Read more: Wadajkar, Aniket S., Jimena G. Dancy, Nathan B. Roberts, Nina P. Connolly, Dudley K. Strickland, Jeffrey A. Winkles, Graeme F. Woodworth, and Anthony J. Kim. "Decreased non-specific adhesivity, receptor targeted (DART) nanoparticles exhibit improved dispersion, cellular uptake, and tumor retention in invasive gliomas." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917308295

“Abstract: The most common and deadly form of primary brain cancer, glioblastoma (GBM), is characterized by significant intratumoral heterogeneity, microvascular proliferation, immune system suppression, and brain tissue invasion. Delivering effective and sustained treatments to the invasive GBM cells intermixed with functioning neural elements is a major goal of advanced therapeutic systems for brain cancer. Previously, we investigated the nanoparticle characteristics that enable targeting of invasive GBM cells. This revealed the importance of minimizing non-specific binding within the relatively adhesive, ‘sticky’ microenvironment of the brain and brain tumors in particular. We refer to such nanoformulations with decreased non-specific adhesivity and receptor targeting as ‘DART’ therapeutics. In this work, we applied this information toward the design and characterization of biodegradable nanocarriers, and in vivo testing in orthotopic experimental gliomas. We formulated particulate nanocarriers using poly(lactic-co-glycolic acid) (PLGA) and PLGA-polyethylene glycol (PLGA-PEG) polymers to generate sub-100 nm nanoparticles with minimal binding to extracellular brain components and strong binding to the Fn14 receptor – an upregulated, conserved component in invasive GBM. Multiple particle tracking in brain tissue slices and in vivo testing in orthotopic murine malignant glioma revealed preserved nanoparticle diffusivity and increased uptake in brain tumor cells. These combined characteristics also resulted in longer retention of the DART nanoparticles within the orthotopic tumors compared to non-targeted versions. Taken together, these results and nanoparticle design considerations offer promising new methods to optimize therapeutic nanocarriers for improving drug delivery and treatment for invasive brain tumors. Graphical abstract: Fn14-targeted nanoparticles bind specifically to Fn14 receptor but not to brain ECM and are retained in invasive intracranial tumors over significantly longer periods than non-targeted nanoparticles. Keywords: Glioblastoma; Invasive malignant glioma; Biodegradable nanoparticles; Targeted therapeutics; Fibroblast growth factor-inducible 14; Multiple particle tracking; Surface plasmon resonance”


These posts are syndicated from John Garner's blog at http://jgakinainc.blogspot.com/.

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