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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-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”


PLGA-PEG-Mal from PolySciTech used in development of curcumin nanoparticles for brain-cancer treatment

Wednesday, September 6, 2017, 9:48 PM ET


Curcumin is a powerful anti-inflammatory agent found in turmeric that prevents cancer metastasis and can aid in treatment of cancer. Due to its extremely poor absorption and low water solubility, simply eating turmeric or taking curcumin as a supplement will not provide adequate curcumin levels to cancerous cells to be of any therapeutic effect. Pairing this agent with a delivery system, however, can leverage its potential as an anticancer compound. Recently, researchers at Yantai University, Luye Pharmaceutical Co, Lunan Pharmaceutical Group, and Binzhou Medical University (China) utilized PLGA-PEG-Mal (PolyVivo AI020) from PolySciTech (www.polyscitech.com) to create a targeted delivery nanoparticle for curcumin to glioma cells. This research holds promise to provide for additional treatment options for brain-cancer. Read more: Zhang, Xuemei, Xuejuan Li, Hongchen Hua, Aiping Wang, Wanhui Liu, Youxin Li, Fenghua Fu, Yanan Shi, and Kaoxiang Sun. "Cyclic hexapeptide-conjugated nanoparticles enhance curcumin delivery to glioma tumor cells and tissue." International Journal of Nanomedicine 12 (2017): 5717. http://pubmedcentralcanada.ca/pmcc/articles/PMC5557616/

“Glioma has one of the highest mortality rates among primary brain tumors. The clinical treatment for glioma is very difficult due to its infiltration and specific growth locations. To achieve improved drug delivery to a brain tumor, we report the preparation and in vitro and in vivo evaluation of curcumin nanoparticles (Cur-NPs). The cyclic hexapeptide c(RGDf(N-me) VK)-C (cHP) has increased affinity for cells that overexpress integrins and was designed to target Cur-NPs to tumors. Functional polyethyleneglycol-modified poly(d,l-lactide-co-glycolide) (PEG-PLGA) conjugated to cHP was synthesized, and targeted Cur-NPs were prepared using a self-assembly nanoprecipitation process. The physicochemical properties and the in vitro cytotoxicity, accuracy, and penetration capabilities of Cur-NPs targeting cells with high levels of integrin expression were investigated. The in vivo targeting and penetration capabilities of the NPs were also evaluated against glioma in rats using in vivo imaging equipment. The results showed that the in vitro cytotoxicity of the targeted cHP-modified curcumin nanoparticles (cHP/Cur-NPs) was higher than that of either free curcumin or non-targeted Cur-NPs due to the superior ability of the cHP/Cur-NPs to target tumor cells. The targeted cHP/Cur-NPs, c(RGDf(N-me)VK)-C-modified Cur-NPs, exhibited improved binding, uptake, and penetration abilities than non-targeting NPs for glioma cells, cell spheres, and glioma tissue. In conclusion, c(RGDf(N-me)VK)-C can serve as an effective targeting ligand, and cHP/Cur-NPs can be exploited as a potential drug delivery system for targeting gliomas. Keywords: glioma targeting, integrin targeting, c(RGDf(N-me)VK)-C peptide, curcumin nanoparticles, in vitro and in vivo evaluation”


PASP from PolySciTech used in SiRNA delivery research

Wednesday, September 6, 2017, 9:47 PM ET


Silencing RNA (siRNA) is short segments of RNA which bind to formed RNA and prevent specific genes from being expressed. This is a powerful tool in gene therapy however the siRNA is very delicate and susceptible to degradation. For this reason, it requires advanced delivery systems. Recently, researchers at Hoshi University and Osaka University (Japan) utilized poly-(α,β)-dl-aspartic acid (PolyVivo Cat# AO005) from PolySciTech (www.polyscitech.com) as part of their investigation into the biodistribution of siRNA drug-delivery systems in-vivo. This research holds promise to enable therapeutic effects of this technology. Read more: Hattori, Yoshiyuki, Ayako Nakamura, Shiori Hanaya, Yuta Miyanabe, Yuki Yoshiike, Takuto Kikuchi, Kei-ichi Ozaki, and Hiraku Onishi. "Effect of chondroitin sulfate on siRNA biodistribution and gene silencing effect in mice after injection of siRNA lipoplexes." Journal of Drug Delivery Science and Technology (2017). http://www.sciencedirect.com/science/article/pii/S1773224717305051


“Abstract: Previously, we found that intravenous injection of chondroitin sulfate (CS), followed by intravenous injection of siRNA/cationic liposome complexes (siRNA lipoplexes) could deliver siRNAs to the liver and suppress expression of target genes. Here, we examined the effect of injection order of CS and siRNA lipoplexes on the biodistribution of siRNA and gene silencing in the liver after sequential injection. When siRNA lipoplexes were injected intravenously into mice, the siRNA largely accumulated in the lungs. However, injection of siRNA lipoplexes, followed by injection of CS, reduced siRNA accumulation in the lungs and increased it in the liver. In addition, agglutinates of erythrocytes caused by the addition of siRNA lipoplexes were re-dispersed by the addition of CS, indicating that the agglutinates accumulating in the lungs by injection of siRNA lipoplexes were broken up by CS injection. However, injection of apolipoprotein B (ApoB) siRNA lipoplexes, followed by injection of CS did not suppress ApoB mRNA levels in the liver. From there results on sequential injection, the injection order of CS and siRNA lipoplexes was important for gene silencing effects in the liver, although the sequential injection could deliver siRNA efficiently into the liver regardless of the injection order of CS and siRNA lipoplexes. Keywords: siRNA delivery; Liposome; Chondroitin sulfate; Liver; Gene silencing”


Whitepaper available on speeding up thermogel dissolution in cold water.

Friday, September 1, 2017, 5:11 PM ET


One drawback of using PLGA-PEG-PLGA and other thermogels is the long time necessary to dissolve them in water. Often, this can be upwards of two days. Recent testing at Akina has found that this time can be cut from 2 days down to around 2 hours by mixing these polymers with PEG-400 biocompatible solvent. Read more here (http://akinainc.com/pdf/WhitePaper-Thermogel-additives-dissolution-effects.pdf).


mPEG-PLLA from PolySciTech used in development of phosphovalproic acid based pancreatic cancer treatment

Friday, September 1, 2017, 4:56 PM ET



The word “cancer” actually describes a broad range of diseases that can affect many different parts of the body. Some cancers, such as skin cancer, respond well to treatment by conventional therapies and have a good prognosis. Other cancers, notably pancreatic, are very difficult to treat and often prove fatal. Recently, researchers working at Stony Brook University, University of Louisiana, and University of California utilized PEG-PLLA (Polyvivo AK004) from PolySciTech (www.polyscitech.com) as part of developing a nanoparticle-based phosphovalproic acid delivery system for treating pancreatic cancer. The developed system showed promise in an animal model for preventing the growth of pancreatic cancer. This research holds promise for a treatment to this lethal disease. Read more: Mattheolabakis, George, Ruixue Wang, Basil Rigas, and Gerardo G. Mackenzie. "Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly (ethylene glycol) nanoparticles." International Journal of Oncology. https://www.spandidos-publications.com/10.3892/ijo.2017.4103/download


“Pancreatic cancer (PC) is one of the most difficult cancers to treat. Since the current chemotherapy is inadequate and various biological approaches have failed, the need for agents that have a potential to treat PC is pressing. Phospho-valproic acid (P-V), a novel anticancer agent, is efficacious in xenograft models of human PC and is apparently safe. In the present study, we evaluated whether formulating P-V in nanoparticles could enhance its anticancer efficacy. In a mouse model of Kras/pancreatitis-associated PC, P-V, orally administered, inhibited the incidence of acinar-to-ductal metaplasia by 60%. To improve its efficacy, we formulated P-V in five different polymeric nanoparticles. Poly-(L)-lactic acid- poly(ethylene glycol) (PLLA-PEG) nanoparticles proved the optimal formulation. PLLA-PEG improved P-V's pharmacokinetics in mice enhancing the levels of P-V in blood. Compared to control, P-V formulated in PLLA-PEG suppressed the growth of MIA PaCa-2 xenografts by 81%, whereas P-V alone reduced it by 51% (p<0 .01="" 87="" a="" acinar-to-ductal="" activated="" against="" agent="" and="" at="" both="" by="" conclusion="" disease="" efficacy="" enhances="" font="" formulated="" formulation="" furthermore="" improving="" in="" inhibited="" is="" it="" its="" kras="" metaplasia="" mice="" models="" molecular="" nanoparticles="" of="" p-v.="" p-v="" p="" pc="" pharmacokinetics.="" phosphorylation="" pivotal="" plla-peg="" promising="" reducing="" residues="" ser727="" stat3="" suppressed="" target="" the="" tyr705="" with="">


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

Wednesday, August 23, 2017, 3:52 PM ET



Triple negative breast cancer is a specific type of cancer which does not have estrogen, progesterone, or HER2 receptors. This type of breast cancer is typically resistant to receptor-targeted treatments and tends to be more highly invasive than other kinds of breast cancer. One powerful form of treatment for this cancer requires sequential treatment with chemotherapeutics to maximize the effectiveness of the administered drugs. Recently, researchers at University of Cincinnati and The Cincinnati Veteran’s Hospital utilized PLA (PolyVivo AP128) from PolySciTech (www.polyscitech.com) as part of their work in generating nanoparticles which provide for time-controlled release of Erlotinib and Doxorubicin to treat triple-negative breast cancer. These nanoparticles release the Erlotinib as an initial burst followed by sustained release of the Doxorubicin. This research holds promise to treat this highly invasive form of breast cancer. Read more: Zhou, Zilan, Carly Kennell, Mina Jafari, Joo-Youp Lee, Sasha J. Ruiz-Torres, Susan E. Waltz, and Jing-Huei Lee. "Sequential Delivery of Erlotinib and Doxorubicin for Enhanced Triple Negative Breast Cancer Treatment Using Polymeric Nanoparticle." International Journal of Pharmaceutics (2017). (http://www.sciencedirect.com/science/article/pii/S0378517317306944)

“Abstract: Recent studies of signaling networks point out that an order of drugs to be administrated to the cancerous cells can be critical for optimal therapeutic outcomes of recalcitrant metastatic and drug-resistant cell types. In this study, a development of a polymeric nanoparticle system for sequential delivery is reported. The nanoparticle system can co-encapsulate and co-deliver a combination of therapeutic agents with different physicochemical properties [i.e. epidermal growth factor receptor (EGFR) inhibitor, erlotinib (Ei), and doxorubicin (Dox)]. Dox is hydrophilic and was complexed with anionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA), via ion pairing to form a hydrophobic entity. Then it was co-encapsulated with hydrophobic Ei in a poly(L-lactide)-b-polyethylene glycol (PLA-b-PEG) nanoparticle by nanoprecipitation. The complexation of Dox with DOPA greatly helps the encapsulation of Dox, and substantially reduces the release rate of Dox. This nanoparticle system was found to burst the release of Ei with a slow and sustained profile of Dox, which is an optimal course of administration for these two drugs as previously reported. The efficacy of this sequential delivery nanoparticle system was validated in vitro and its in vivo potential applicability was substantiated by fluorescent imaging of high tumor accumulation. Keywords: Nanoparticle, Combination therapy, Sequential delivery, Triple negative breast cancer, EGFR, inhibitor, Erlotinib, Doxorubicin”


PolySciTech mPEG-PLGA/PLGA-rhodamine used in the development of nanoparticle-based intracellular MRSA treatment

Tuesday, August 15, 2017, 4:07 PM ET


MRSA is a bacterial infection that is highly resistant to conventional antibiotic treatments or other therapies. It is still affected by vancomycin, but the bacterial spores have the capability to ‘hide’ inside of cells making it very difficult to treat. One means around this is to use nanoparticles for delivery of the antibiotic to the cells to ensure suitable vancomycin in a local concentration to kill off the bacteria. Recently, researchers at Purdue University used mPEG-PLGA (Polyvivo AK030) and rhodamine-B labelled PLGA (PolyVivo AV011) from PolySciTech (www.polyscitech.com) to create pH sensitive nanoparticles designed for intracellular delivery of vancomycin. This research holds promise to improve treatments of this deadly bacterial infection. Read more: Pei, Yihua, Mohamed F. Mohamed, Mohamed N. Seleem, and Yoon Yeo. "Particle engineering for intracellular delivery of vancomycin to methicillin-resistant Staphylococcus aureus (MRSA)-infected macrophages." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917307745


“Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a serious threat to the public health. MRSA is particularly difficult to treat when it invades host cells and survive inside the cells. Although vancomycin is active against MRSA, it does not effectively kill intracellular MRSA due to the molecular size and polarity that limit its cellular uptake. To overcome poor intracellular delivery of vancomycin, we developed a particle formulation (PpZEV) based on a blend of polymers with distinct functions: (i) poly(lactic-co-glycolic acid) (PLGA, P) serving as the main delivery platform, (ii) polyethylene glycol-PLGA conjugate (PEG-PLGA, p) to help maintain an appropriate level of polarity for timely release of vancomycin, (iii) Eudragit E100 (a copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate, E) to enhance vancomycin encapsulation, and (iv) a chitosan derivative called ZWC (Z) to trigger pH-sensitive drug release. PpZEV NPs were preferentially taken up by the macrophages due to its size (500–1000 nm) and facilitated vancomycin delivery to the intracellular pathogens. Accordingly, PpZEV NPs showed better antimicrobial activity than free vancomycin against intracellular MRSA and other intracellular pathogens. When administered intravenously, PpZEV NPs rapidly accumulated in the liver and spleen, the target organs of intracellular infection. Therefore, PpZEV NPs is a promising carrier of vancomycin for the treatment of intracellular MRSA infection. Keywords: Nanoparticles, Intracellular drug delivery, pH-sensitive, Macrophages, Intracellular MRSA, Vancomycin”


Improved targeted-delivery system using oriented antibody fragments developed using PLGA-PEG-Azide from PolySciTech.

Monday, August 14, 2017, 2:43 PM ET



A powerful tool for medicinal delivery is the use of a nanoparticle with a surface covered in a specific antibody or targeting ligand. Because these antibodies and ligands bind specifically to certain protein factors these can be tailored to target to specific cells, notably cancer cells. Since antibody bonding is a stereochemical process, shape and orientation of the antibody matters in terms of its capability to bind. If the active site of the ligand is facing inwards, towards the nanoparticle, it may not work well at all. Recently, researchers working at Queen's University Belfast, University College London, (UK) and Universidade de Lisboa (Portugal) used PLGA-PEG-Azide from PolySciTech (www.polyscitech.com, PolyVivo AI085) to generate nanoparticles which had very precisely controlled antibody orientation on their surface allowing for improved functionality and targeting. They tested this system for its ability to bind to HER2 (a factor that is overexpressed in cancer cells) and found it had substantially higher binding than a randomly oriented nanoparticle system. This research holds promise for developing a wide-array of targeted delivery systems for treating a variety of diseases, most notably cancer. Read more: M. Greene, D. A. Richards, J. Nogueira, K. Campbell, P. Smyth, M. Fernandez, C. J. Scott and V. Chudasama “Generating Next-Generation Antibody-Nanoparticle Conjugates through the Oriented Installation of Non-Engineered Antibody Fragments” Chem. Sci., 2017, DOI: 10.1039/C7SC02747H. (http://pubs.rsc.org/en/Content/ArticleLanding/2017/SC/C7SC02747H#!divAbstract)


“Abstract: The successful development of targeted nanotherapeutics is contingent upon the conjugation of therapeutic nanoparticles to target-specific ligands, with particular emphasis being placed on antibody-based ligands. Thus, new methods that enable the covalent and precise installation of targeting antibodies to nanoparticle surfaces are greatly desired, especially those which do not rely on costly and time-consuming antibody engineering techniques. Herein we present a novel method for the highly controlled and oriented covalent conjugation of non-engineered antibody F(ab) fragments to PLGA-PEG nanoparticles using disulfide-selective pyridazinedione linkers and strain-promoted alkyneazide click chemistry. Exemplification of this method with trastuzumab and cetuximab showed significant improvements in both conjugation efficiency and antigen binding capability, when compared to commonly employed strategies for antibody-nanoparticle construction. This new approach paves the way for the development of antibody-targeted nanomedicines with improved paratope availability, reproducibility and uniformity to enhance both biological activity and ease of manufacture.”


PolySciTech PLGA-NH2 used in research thesis on nanoparticle-surface interactions with living cells

Friday, August 11, 2017, 3:35 PM ET



Nanoparticles have been around for many years but we are still, as a species, just scratching at the surface of understanding them. Of course, the surface is the most important part of a nanoparticle since, due to their incredibly small size, they have an incredible surface area to volume ratio. For example, 1g of PLGA nanoparticles (100 nm) would have a surface area of 7.8 square meters (a little larger than a typical parking space for a car). For this reason, the surface and how it interacts with living organisms is the most important aspect of nanoparticle technology. Recently, Angie (Morris) Thorn at University of Iowa published a PhD thesis which details efforts to broaden our understanding of nanoparticle surface interactions with cells. This includes work with PLGA-NH2 (PolyVivo AI063) from PolySciTech (www.polyscitech.com) to generate nanoparticles covered with either chitosan (for mucoadhesion) or TPP (mitochondria-targeting) to create targeted nanoparticles as drug-delivery vectors. Read more: Thorn, Angie Sue Morris. "The impact of nanoparticle surface chemistry on biological systems." (2017). http://ir.uiowa.edu/etd/5659/

“Abstract: The unique properties of nanomaterials, such as their small size and large surface area-to-volume ratios, have attracted tremendous interest in the scientific community over the last few decades. Thus, the synthesis and characterization of many different types of nanoparticles has been well defined and reported on in the literature. Current research efforts have redirected from the basic study of nanomaterial synthesis and their properties to more application-based studies where the development of functionally active materials is necessary. Today such nanoparticle-based systems exist for a range of biomedical applications including imaging, drug delivery and sensors. The inherent properties of the nanomaterial, although important, aren’t always ideal for specific applications. In order to optimize nanoparticles for biomedical applications it is often desirable to tune their surface properties. Researchers have shown that these surface properties (such as charge, hydrophobicity, or reactivity) play a direct role in the interactions between nanoparticles and biological systems can be altered by attaching molecules to the surface of nanoparticles. In this work, the effects of physicochemical properties of a wide variety of nanoparticles was investigated using in vitro and in vivo models. For example, copper oxide (CuO) nanoparticles were of interest due to their instability in biological media. These nanoparticles undergo dissolution when in an aqueous environment and tend to aggregate. Therefore, the cytotoxicity of two sizes of CuO NPs was evaluated in cultured cells to develop a better understanding of how these propertied effect toxicity outcomes in biological systems. From these studies, it was determined that CuO NPs are cytotoxic to lung cells in a size-dependent manner and that dissolved copper ions contribute to the cytotoxicity however it is not solely responsible for cell death. Moreover, silica nanoparticles are one of the most commonly used nanomaterials because they are easy to synthesize and their properties (such as size, porosity and surface chemistry) can be fine-tuned. Silica nanoparticles can be found in thousands of commercially available products such as toothpastes, cosmetics and detergents and are currently being developed for biomedical applications such as drug delivery and biomedical imaging. Our findings herein indicate that the surface chemistry of silica nanoparticles can have an effect on lung inflammation after exposure. Specifically, amine-modified silica NPs are considered to be less toxic compared to bare silica nanoparticles. Together, these studies provide insight into the role that material properties have on toxicity and allow for a better understanding of their impact on human and environmental health. The final aim of this thesis was to develop surface-modified nanoparticles for drug delivery applications. For this, biodegradable, polymeric NPs were used due to their inert nature and biocompatibility. Furthermore, polymeric NPs are excellent for loading drugs and using them as drug delivery vehicles. In this work, poly (lactic-co-glycolic acid) (PLGA) NPs were loaded with a therapeutic peptide. These NPs were then coated with chitosan (a mucoadhesive polymer) for the treatment of allergic asthma or coated with a small cationic mitochondrial targeting agent for the treatment of ischemia/reperfusion injury. Taken as a whole, this thesis sheds light on the impact of NPs on human health. First by providing useful toxological data for CuO and silica NPs as well as highlighting the potential of surface-modified polymeric NPs to be used in drug delivery-based applications. Keywords: Cell Culture, Nanoparticle, Toxicity”


PEG-PLGA/PLGA from PolySciTech used by Precision NanoSystems, Inc. as part of microfluidics NanoAssemblr™ method optimization and testing

Friday, July 28, 2017, 3:09 PM ET



Microfluidics references the use of systems which have extremely small fluid-channels on the order of magnitude of microns in scale. Precision NanoSystems, Inc. is a company which has developed an array of microfluidic instruments and machines designed for a variety of applications including the synthesis of micro and nanoparticles. For generating micro/nano-particles of polymers, the typical process is to dissolve the polymer in an organic solvent and then mix it with water so that the polymer (which is not water soluble) precipitates out into sub-micron sized particles. Unlike simple emulsion, where the solvent and water are randomly mixed together, the mixing of the organic phase with the water phase in a microfluidics system is highly controlled which allows for the generation of very precise micro/nanoparticles. Recently, Precision Nanosystems, Inc. used a series of mPEG-PLGA’s from PolySciTech (www.polyscitech.com, PolyVivo AK010, AK037, AK106) to make a series of test pegylated nanoparticles with highly controlled properties. They reported these results in a scientific poster presented at controlled release society (CRS) 2017 meeting. This research holds promise for a wide array of applications involving the use of nanoparticles/microparticles as drug delivery systems. Read more here: S.M. Garg, M. Parmar, A. Thomas, E. Ouellet, M. Deleonardis, P. Johnson, A. Armstead, S. Ip, T.J. Leaver, A.W. Wild, R.J. Taylor, E.C. Ramsay “Microfluidics-based Manufacture of PEG-b-PLGA Block Copolymer Nanoparticles for the Delivery of Small Molecule Therapeutics” Controlled Release Society 2017 Poster Session. (https://www.precisionnanosystems.com/resources/?_sf_s=PEG-b-PLGA&_sft_resource-type=poster)

“(Poster introduction): Purpose: In recent years, numerous methods have been developed for the production of block copolymer nanoparticles as drug delivery vehicles. However, these methods pose numerous challenges in maintaining consistent nanoparticle quality, tuning size depending on the application, optimization for scale-up, and reproducibility. The NanoAssemblr™ platform is an automated microfluidics-based system that eliminates user variability and is capable of reproducible, and scalable manufacture of nanoparticles. Here, we describe the use of microfluidic mixing to manufacture PEG-b-PLGA nanoparticles using the NanoAssemblr™ Benchtop instrument. We further describe optimization strategies and investigate the physical encapsulation of a hydrophobic model drug coumarin-6.Results: Microfluidic mixing enabled the rapid and consistent manufacturing of PEG-b-PLGA nanoparticles having diameters below 100 nm. Instrument parameters such as aqueous:organic Flow Rate Ratio and Total Flow Rate had a significant impact on the size of the resulting nanoparticles. Increasing the molecular weight of the PLGA block from 10000 - 95000 Da resulted in an increase in the size of the nanoparticles from 40 - 80 nm. However, changes in the total flow rate of the instrument enabled all the nanoparticles to be tuned to a similar size of 60 nm which is difficult to control using conventional techniques. Coumarin-6 was successfully loaded into PEG-b-PLGA nanoparticles with an encapsulation efficiency of 52% w/w which was significantly higher than that obtained by co-solvent evaporation technique (34% w/w). The size of the nanoparticles prepared using the NanoAssemblr platform were tunable over a broad range while co-solvent evaporation does not provide a reliable means to tune size.”

In addition to this poster, Precision Nanosystems, Inc. has utilized PLGA from PolySciTech (PolyVivo AP121) in generating a wide array of technical data relevant to their microfluidic system. You can see these technical whitepapers here (https://www.precisionnanosystems.com/resources/?_sf_s=plga&_sft_resource-type=tech-bulletins-and-white-papers)


PLA-amine from PolySciTech used in development of atherosclerosis-targeted nanoparticles for treatment of heart disease

Tuesday, July 25, 2017, 2:27 PM ET



Heart disease, typically due to atherosclerotic lesions, is one of the leading causes of death in USA. Most treatments for this disease focus on surgical interventions (e.g. stent placement), which is often utilized in acute situations, or on systemic medicines such as statins, which are typically applied as a preventative. There is a need for therapies to be applied in non-emergency situations but where atherosclerotic lesions are known to be present. Conventionally, nanoparticles have been applied for use against cancer, however they can be targeted to lesions by using appropriate targeting moieties. Recently, researchers working jointly at Harvard Medical School, New York University, Technical University of Denmark, Korea Institute of Ceramic Engineering and Technology, Korea Advanced Institute of Science and Technology, and King Abdulaziz University used PLA-NH2 (PolyVivo AI041, www.polyscitech.com) from PolySciTech as a reactive precursor for generating a fluorescently-conjugated tracer as part of a novel nanoparticle-based system for treatment of artherosclerosis. Read more: Yu, Mikyung, Jaume Amengual, Arjun Menon, Nazila Kamaly, Felix Zhou, Xiaoding Xu, Phei Er Saw et al. "Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr−/− Mice." Advanced Healthcare Materials (2017). http://onlinelibrary.wiley.com/doi/10.1002/adhm.201700313/full

“Abstract: The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized. In vitro studies indicate that the GW-encapsulated NPs upregulate the LXR target genes and downregulate proinflammatory mediator in macrophages. The Col IV-targeted NPs encapsulating GW (Col IV–GW–NPs) successfully reaches atherosclerotic lesions when administered for 5 weeks to mice with preexisting lesions, substantially reducing macrophage content (≈30%) compared to the PBS group, which is with greater efficacy versus nontargeting NPs encapsulating GW (GW–NPs) (≈18%). In addition, mice administered the Col IV–GW–NPs do not demonstrate increased hepatic lipid biosynthesis or hyperlipidemia during the treatment period, unlike mice injected with the free GW. These findings suggest a new form of LXR-based therapeutics capable of enhanced delivery of the LXR agonist to atherosclerotic lesions without altering hepatic lipid metabolism.”


Protein phosphorylation assay kits by Tymora Analytical now available through PolySciTech

Thursday, July 20, 2017, 9:20 AM ET



The selective phosphorylation of proteins is a key step in many pathways regulating their functions. Abnormal phosphorylation is involved in a wide variety of diseases including cancer. To perform antibody labeling, an effective antibody has to be made for each phosphorylated protein, which is an expensive and time-consuming process. Recently, Tymora Analytical has developed a titanium-based reagent assay kit to allow for detection of protein phosphorylation in a rapid, efficient, and sensitive assay. Due to a recent distribution agreement, these products are now available through PolySciTech division of Akina, Inc. (https://akinainc.com/polyscitech/products/tymora/). Learn more about this powerful assay method in a recent publication here: Iliuk, Anton, Li Li, Michael Melesse, Mark C. Hall, and W. Andy Tao. "Multiplexed Imaging of Protein Phosphorylation on Membranes Based on TiIV Functionalized Nanopolymers." ChemBioChem 17, no. 10 (2016): 900-903. http://europepmc.org/articles/4870103

“Abstract: Accurate protein phosphorylation analysis reveals dynamic cellular signaling events not evident from protein expression levels. The most dominant biochemical assay, western blotting, suffers from the inadequate availability and poor quality of phospho-specific antibodies for phosphorylated proteins. Furthermore, multiplexed assays based on antibodies are limited by steric interference between the antibodies. Here we introduce a multifunctionalized nanopolymer for the universal detection of phosphoproteins that, in combination with regular antibodies, allows multiplexed imaging and accurate determination of protein phosphorylation on membranes. Keywords: antibodies, dendrimers, membranes, multiplexed analysis, phosphoproteins”


CRS Meeting 2017

Friday, July 14, 2017, 4:32 PM ET


Meet PolySciTech (www.polyscitech.com) at booth 501 at the CRS meeting in Boston next week https://www.controlledreleasesociety.org/meetings/annual/Pages/default.aspx


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

Wednesday, July 12, 2017, 1:01 PM ET


Obesity in humans is a contributing factor to many other health concerns, such as arthritis and cardiovascular problems. Recently, researchers at Purdue University utilized PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AP101) to develop nanoparticles which deliver dibenzazepine to reduce the overgrowth of adipocytes (fat-cells). This research holds promise to provide for improved treatments of obesity. Read more: Jiang, Chunhui, Mario Alberto Cano-Vega, Feng Yue, Liangju Kuang, Naagarajan Narayanan, Gozde Uzunalli, Madeline P. Merkel, Shihuan Kuang, and Meng Deng. "Dibenzazepine-loaded nanoparticles induce local browning of white adipose tissue to counteract obesity." Molecular Therapy (2017). http://www.cell.com/molecular-therapy-family/molecular-therapy/abstract/S1525-0016(17)30256-3


“Inhibition of Notch signaling via systemic drug administration triggers conversion of white adipocytes into beige adipocytes (browning) and reduces adiposity. However, translation of this discovery into clinical practice is challenged by potential off-target side effects and lack of control over the location and temporal extent of beige adipocyte biogenesis. Here, we demonstrate an alternative approach to stimulate browning using nanoparticles (NPs) composed of FDA-approved poly(lactide-co-glycolide) that enable sustained local release of a Notch inhibitor (dibenzazepine, DBZ). These DBZ-loaded NPs support rapid cellular internalization and inhibit Notch signaling in adipocytes. Importantly, focal injection of these NPs into the inguinal white adipose tissue depots of diet-induced obese mice results in localized NP retention and browning of adipocytes, consequently improving the glucose homeostasis and attenuating body-weight gain of the treated mice. These findings offer new avenues to develop a potential therapeutic strategy for clinical treatment of obesity and its associated metabolic syndrome. Keywords: drug delivery; nanoparticle; browning; adipocyte; Notch signaling; obesity; PLGA; dibenzazepine; adipose tissue; Notch inhibitor”


Tissue scaffolds with improved delivery of growth factor developed using PLGA-PEG-Mal from PolySciTech

Wednesday, July 12, 2017, 1:00 PM ET


A powerful tool in medicine would be the ability to produce a tissue-scaffold which allows for tissue which has been lost due to disease or trauma to be replaced with fresh stem-cells. There are many barriers to the developemtn of this tool one of which is ensuring that the stem-cells have the appropriate anchoring sites as well as the correct growth factors to ensure their appropriate growth and development. Recently, researchers working jointly at Fudan University (China), Tianjin Medical University (China), Ewha Women’s University (Korea), and University of Michigan utilized Maleimide-PEG-PLGA (PolyVivo AI136) and fluorescently conjugated PLGA-FPR648 (Polyvivo AV008) from PolySciTech (www.polyscitech.com) to generate a scaffold which allowed for controlled release of differentiation factors. They used the developed scaffold to repair ischemic tissue in a mouse model. This research holds promise to enable tissue repair and regeneration by successfully growing differentiated stem-cells into damaged areas. Read more: Li, Ruixiang, Zhiqing Pang, Huining He, Seungjin Lee, Jing Qin, Jian Wu, Liang Pang, Jianxin Wang, and Victor C. Yang. "Drug depot-anchoring hydrogel: A self-assembling scaffold for localized drug release and enhanced stem cell differentiation." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S016836591730706X


“Abstract: Localized and long-term delivery of growth factors has been a long-standing challenge for stem cell-based tissue engineering. In the current study, a polymeric drug depot-anchoring hydrogel scaffold was developed for the sustained release of macromolecules to enhance the differentiation of stem cells. Self-assembling peptide (RADA16)-modified drug depots (RDDs) were prepared and anchored to a RADA16 hydrogel. The anchoring effect of RADA16 modification on the RDDs was tested both in vitro and in vivo. It was shown that the in vitro leakage of RDDs from the RADA16 hydrogel was significantly less than that of the unmodified drug depots (DDs). In addition, the in vivo retention of injected hydrogel-incorporated RDDs was significantly longer than that of hydrogel-incorporated unmodified DDs. A model drug, vascular endothelial growth factor (VEGF), was encapsulated in RDDs (V-RDDs) as drug depot that was then anchored to the hydrogel. The release of VEGF could be sustained for 4 weeks. Endothelial progenitor cells (EPCs) were cultured on the V-RDDs-anchoring scaffold and enhanced cell proliferation and differentiation were observed, compared with a VEGF-loaded scaffold. Furthermore, this scaffold laden with EPCs promoted neovascularization in an animal model of hind limb ischemia. These results demonstrate that self-assembling hydrogel-anchored drug-loaded RDDs are promising for localized and sustained drug release, and can effectively enhance the proliferation and differentiation of resident stem cells, thus lead to successful tissue regeneration. Graphical abstract: Schematic illustration of a vascular endothelial growth factor (VEGF)-loaded RDDs-anchoring hydrogel. The RADA16 peptide is the basic self-assembling unit forming fiber and constructing hydrogel; poly (lactic-co-glycolic acid) (PLGA) based, VEGF-loaded drug depots (DDs) were modified using the RADA16 peptide (V-RDDs) to anchor them to the skeleton of the hydrogel; PEG was applied as a spacer to ensure the full stretch of the RADA16 peptide. VEGF demonstrated sustained release into the hydrogel to enhance the proliferation and differentiation of resident EPCs. Keywords: PLGA; RADA16 hydrogel; Sustained release; Endothelial progenitor cells; Vascular endothelial growth factor; Tissue regeneration”


mPEG-PLGA from PolySciTech used in development of immune-control treatment for allergic reactions

Wednesday, July 12, 2017, 12:56 PM ET


Allergic contact dermatitis is a common inflammatory skin condition caused by a pathological immune response to a given trigger such as poison ivy oils or nickel metal. This aggravating skin condition can be prevented and treated by reducing the local formation of allergen specific t-cells. Doing so, however, requires careful localized delivery of specific set of molecules including proteins and small-molecule signals to discourage an overly responsive immune attack. This same strategy has great application towards other uses such as autoimmune disease disorders and transplant rejection. Recently, Researchers at University of Pittsburgh used mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK037) to generate microparticles which can locally deliver TGF-β1, Rapamycin, and IL-2 to the skin. They discovered these particles were successful in prevent or reversing allergic responses in sensitized mice. This research holds promise to treat a wide-array of immune-mediated disease state. Read more: Balmert, Stephen C., Cara Donahue, John R. Vu, Geza Erdos, Louis D. Falo, and Steven R. Little. "In vivo induction of regulatory T cells promotes allergen tolerance and suppresses allergic contact dermatitis." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917307046

“Abstract: Allergic contact dermatitis (ACD) is a common T-cell mediated inflammatory skin condition, characterized by an intensely pruritic rash at the site of contact with allergens like poison ivy or nickel. Current clinical treatments use topical corticosteroids, which broadly and transiently suppress inflammation and symptoms of ACD, but fail to address the underlying immune dysfunction. Here, we present an alternative therapeutic approach that teaches the immune system to tolerate contact allergens by expanding populations of naturally suppressive allergen-specific regulatory T cells (Tregs). Specifically, biodegradable poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA) microparticles were engineered to release TGF-β1, Rapamycin, and IL-2, to locally sustain a microenvironment that promotes Treg differentiation. By expanding allergen-specific Tregs and reducing pro-inflammatory effector T cells, these microparticles inhibited destructive hypersensitivity responses to subsequent allergen exposure in an allergen-specific manner, effectively preventing or reversing ACD in previously sensitized mice. Ultimately, this approach to in vivo Treg induction could also enable novel therapies for transplant rejection and autoimmune diseases.”



mPEG-PLGA from PolyScitech used in development of dual-drug nanotherapy treatment for non-small cell lung cancer

Friday, July 7, 2017, 4:04 PM ET



Non-small cell lung cancer is an extremely prevelant type of cancer with over 200K cases in the USA per year. Typically it is treated using chemotherapy and radiotherapy, but the incidence of reoccurrence is quite high after these therapies. Recently, researchers working jointly at University of North Carolina, Tiangin Vocational Institute (China), Westminster College, China Medical University, and Peking Union Medical College (China) used mPEG-PLGA from PolySciTech (www.polyscitech.com) (PolyVivo AK029) to develop a co-encapsulated nanoparticle loaded with paclitaxel and a cisplatin prodrug. They applied this to a mouse model of lung cancer and found the particles reduced tumor growth more effectively than loose drug administration. This research holds promise to improve the treatment of lung cancer. Read more: Jing Tian, Yuanzeng Min, Zachary Rodgers, Kin Man Au, Charles Tilden Hagan, Maofan Zhang, Kyle Roche, Feifei Yang, Kyle Thomas Wagner and Andrew Z Wang “Co-delivery of paclitaxel and cisplatin with biocompatible PLGA-PEG nanoparticles enhances chemoradiotherapy in non-small cell lung cancer models.” J. Mater. Chem. B, 2017, Accepted Manuscript. DOI 10.1039/C7TB01370A http://pubs.rsc.org/en/content/articlelanding/2017/tb/c7tb01370a#!divAbstract

“Abstract: Chemoradiotherapy (CRT) with paclitaxel (PTX) and cisplatin (CP) is part of the standard of care for patients with locally advanced non-small cell lung cancer (NSCLC). Despite the high treatment intensity, many patients still develop local recurrence after treatment. Thus, there is a strong need to further improve CRT for lung cancer. One strategy is to co-deliver cytotoxic chemotherapy agents using biocompatible nanoparticles (NPs) which can limit off-target tissue toxicity and improve therapeutic efficacy. Herein, we report the development of dual-drug loaded nanoformulations that improve the efficacy of CRT for NSCLC by co-encapsulation of cisplatin (CP) and PTX in PLGA-PEG NPs. Mice bearing NSCLC xenografts given the dual-drug loaded NPs during CRT showed greater inhibition of tumor growth than free drug combinations or combinations of single-drug loaded NPs. These results indicate that using a NP co-delivery strategy for this common CRT regimen may improve clinical responses in NSCLC patients. Supplementary details http://www.rsc.org/suppdata/c7/tb/c7tb01370a/c7tb01370a1.pdf
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Akina, Inc. Closed for Independence Day.

Tuesday, July 4, 2017, 10:39 AM ET


Akina, Inc. is closed for USA independence day July 4th. We will reopen from July 5th. Any orders placed will be processed then.


Immunotherapy research using PLGA, PLGA-PEG-maleimide, and PLGA-rhodamine from PolySciTech shows promise for cancer treatment

Monday, July 3, 2017, 2:23 PM ET



Treatment of cancer remains difficult due to a wide variety of reasons. One problem is that, typically, cancer tends to metastasize and spread so that there are smaller tumors, tendrils or clumps of tumor cells instead of a singular, lone cancer tumor. These ‘satellite tumors’ can remain even after the main tumor has been removed by surgery or other process. Radiation and chemotherapy treatments can affect nearby cancer cells, by the absopal effect, but this effect is relatively weak and often these smaller tumor portions regrow to form new cancer tumors. A good strategy for destroying cancer, both main tumor and nearby satellite tumors, is to utilize immunotherapy. This process effectively ‘vaccinates’ the body so that the immune system attacks the cancer as if it is an invasive pathogen. Recently, researchers working jointly at University of North Carolina, Duke University, Xuzhou Medical University (Japan), North Carolina Sate University, and the Memorial Sloan-Kettering Cancer Center developed a novel antigen-capturing-nanoparticle based immunotherapy treatment for cancer treatment. This therapy relies on nanoparticles capturing the antigens from the tumor and then presenting those to immunce cells to elicit an immune response. For this research, they used PLGA (AP059), mPEG-PLGA (AK037), PLGA-PEG-NH2 (AI058), PLGA-PEG-Mal (AI052) and poly(lactide-co-glycolide)-rhodamine B (AV011) from PolySciTech (www.polyscitech.com) to generate these nanoparticles and to track them by fluorescence, respectively. This research holds promise for improved cancer therapy. Read more: Min, Yuanzeng, Kyle C. Roche, Shaomin Tian, Michael J. Eblan, Karen P. McKinnon, Joseph M. Caster, Shengjie Chai et al. "Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy." Nature Nanotechnology (2017). (https://www.nature.com/nnano/journal/vaop/ncurrent/full/nnano.2017.113.html)

“Immunotherapy holds tremendous promise for improving cancer treatment1. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the ‘abscopal effect’. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties. We showed that AC-NPs deliver tumour-specific proteins to antigen-presenting cells (APCs) and significantly improve the efficacy of αPD-1 (anti-programmed cell death 1) treatment using the B16F10 melanoma model, generating up to a 20% cure rate compared with 0% without AC-NPs. Mechanistic studies revealed that AC-NPs induced an expansion of CD8+ cytotoxic T cells and increased both CD4+T/Treg and CD8+T/Treg ratios (Treg, regulatory T cells). Our work presents a novel strategy to improve cancer immunotherapy with nanotechnology. Subject terms: Drug delivery Nanotechnology in cancer”


PolySciTech certificates of analysis now available directly on the website

Monday, June 26, 2017, 1:28 PM ET


All materials generated by the PolySciTech division of Akina, Inc. (www.polyscitech.com) undergo a rigorous set of chemical characterization tests. These typically include Fourier-transform infrared spectrophotometry (FTIR) scan, proton nuclear magnetic resonance (HNMR), and gel-permeation chromatography (GPC). The FTIR test gives information on specific chemical moieties included in the material based on their particular absorption peaks/bands. The HNMR test provides further chemical characterization by providing peaks which correspond to specific shifts based on hydrogen local environment. This also allows for proton-counting to be used for determining polymer features. For example the lactide-to-glycolide ratio in PLGA can be determined by comparing the peak integration at 5.2 ppm (1H, lactide) with the integration at 4.8 (2H, glycolide). Gel-permeation chromatography yields data on the molecular weight of the polymer as well as the distribution of polymer chain lengths. The data from these tests are shown directly on the certificate of analysis (COA) to provide the customer with a thorough set of chemical characterization data. Recently, Akina, Inc. has compiled the COAs for both currently available batches as well as historical batches of material into an online, searchable format. This allows for pulling up data both on historical batches purchased some time ago as well as reviewing COAs for current materials. Note that, as long as enough material is in stock to fill the order, you can request a specific batch on an order at no additional charge by indicating the batch on the order or in the ‘Special notes’ section on the online order form. See the searchable set of COAs here (https://akinainc.com/polyscitech/products/polyvivo/COA.php)



Synthesize like a pro with reactive intermediates generated by award-winning researchers

Friday, June 23, 2017, 4:28 PM ET



Akanocure Pharmaceuticals, a Purdue University spin-off company, has won several awards including the Purdue Ag-celerator award, FOUNDER.org award, as well as has been a finalist in the MassChallenge Boston competition. This company, founded by Sherine Abdelmawla, Mohammad Noshi, and Philip Fuchs, generates novel synthetic methodologies to recreate naturally occurring compounds. These synthetic compounds can be used for a wide-variety of therapeutic applications including cancer treatments. The process begins with specific precursors that have defined stereochemistry so that the exact chiral-structure of the molecule is defined ensuring appropriate bioactivity. These custom-developed precursors are lactone derivatives with precisely controlled protecting units at specific locations, can be utilized to generate a broad range of molecules. These unique chemicals are commercially distributed through Akina, Inc. PolySciTech Division (https://akinainc.com/polyscitech/products/akanocure/index.php) and can be used in your lab for generating a wide array of bioactive molecules. (Photo from www.purduefoundry.com/news)


Cancer nanoparticle-based photodynamic therapy developed using mPEG-PLA from PolySciTech

Tuesday, June 20, 2017, 1:36 PM ET


Treating cancer is complicated by several features of the disease including metastasis, drug-resistance, and biological similarity of cancerous cells to healthy ones. Conventional chemotherapy is typically effective at killing cancer cells, however it lacks the capacity to discriminate between cancerous cells and healthy ones. This is where combination therapies can have an advantage. For phototherapy, instead of delivering a toxic molecule (such as cisplatin or paclitaxel) a photosensitizer is delivered. This molecule is inactive, unless it is activated by a very specific frequency of light which activates it killing the cell. The overall method here is to systematically deliver the photosensitizer to a patient and then selectively illuminate the portion where the cancer is located so only the cancer is affected. Recently, researchers working jointly at Northeastern University, George Washington University, and Wenzhou Medical University utilized mPEG-PLA from PolySciTech (www.polyscitech.com) (PolyVivo AK021) to create protoporphyrin IX (a photosensitizer) loaded nanoparticles. They combined these with photodynamic therapy and tested this system as a treatment for melanoma. This research holds promise to improve the treatment of melanoma, especially malignant or drug-resistant forms. Read more: Wang, Mian, Benjamin M. Geilich, Michael Keidar, and Thomas J. Webster. "Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma." International Journal of Nanomedicine 12 (2017): 4117. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5459981/

“Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT) is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX), an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP) was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed) at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed). With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed) compared to not using a light source (45% were killed) or using a UV light source (65% were killed). In summary, these results indicated for the first time that PpIX-loaded polymersomes together with CAP posttreatment could be a promising tool for skin cancer drug delivery with selective toxicity toward melanoma cells sparing healthy fibroblasts. Keywords: melanoma, polymersomes, protoporphyrin IX, cold atmospheric plasma, photo-dynamic therapy”


PLA from PolySciTech used as precursor for synthesis of environmentally-safe adhesives

Wednesday, June 14, 2017, 2:53 PM ET


Adhesives are used for manufacturing just about everything in our everyday lives. Most of these are petroleum-based materials, which creates an environmental concern due to their chemical off-gassing and lack of degradability. There is an increasing push in polymer science to replace non-degradable synthetics, or petroleum-based materials, with more sustainable alternatives. This becomes increasingly necessary as there is only a limited amount of landfill space available. Poly(lactic acid) (PLA) is a biodegradable polymer which naturally hydrolyzes into non-toxic lactic acid upon contact with water. Lactic acid itself is actually edible (it’s the ingredient that gives Korean kimchi its distinctive tangy-flavor) and can be easily metabolized by a wide variety of organisms back into carbon dioxide and water. For this reason, PLA is a very environmentally safe alternative in comparison to other polymers. However, typical PLA is not considered an adhesive. Recently, researchers at Purdue University utilized several PLAs from PolySciTech (www.polyscitech.com) (PolyVivo Cat# AP035, AP114, and AP138) as precursors to synthesize environmentally-safe poly(lactide)-catechol based adhesives. This research holds promise for the creation of environmentally safe alternatives to petroleum-type adhesives. Read more: Jenkins, Courtney L., Heather M. Siebert, and Jonathan J. Wilker. "Integrating Mussel Chemistry into a Bio-Based Polymer to Create Degradable Adhesives." Macromolecules (2017). http://pubs.acs.org/doi/abs/10.1021/acs.macromol.6b02213

“Adhesives releasing carcinogenic formaldehyde are almost everywhere in our homes and offices. Most of these glues are permanent, preventing disassembly and recycling of the components. New materials are thus needed to bond and debond without releasing reactive pollutants. In order to develop the next generation of advanced adhesives we have turned to biology for inspiration. The bonding chemistry of mussel proteins was combined with preformed poly(lactic acid), a bio-based polymer, by utilizing side reactions of Sn(oct)2, to create catechol-containing copolymers. Structure–function studies revealed that bulk adhesion was comparable to that of several petroleum-based commercial glues. Bonds could then be degraded in a controlled fashion, separating substrates gradually using mild hydrolysis conditions. These results show that biomimetic design principles can bring about the next generation of adhesive materials. Such new copolymers may help replace permanent materials with renewable and degradable adhesives that do not create chronic exposure to toxins.”



PolySciTech PLGA-PEG-PLGA thermogel used in development of equine anti-fungal treatment to prevent blindness both in humans and horses

Thursday, June 8, 2017, 2:16 PM ET



Keratomycosis, is a vision-threatening disease which occurs both in horses and humans. Horses, in particular, tend to be extremely sensitive to fungal diseases such as this and have similar pathology to humans. Voriconazole is commonly applied as an anti-fungal drug, but ocular administration is complicated by poor absorption, tear-excretion, and other factors which make high frequency repeat doses necessary. Unsurprisingly, horses do not typically like to receive eye-drops and administering medicine by this method is not a trivial task. There is a need to generate an extended release formulation for their treatment. Recently, researchers at Auburn University, and University of Queensland (Australia) utilized PLGA-PEG-PLGA thermogels from PolySciTech (www.polyscitech.com) (PolyVivo AK024, and AK019) to generate a Voriconazole loaded thermogel. They tested this gel formulation for delivery kinetics and safety. This research holds promise to provide treatment for this disease which can lead to blindness in both humans and horses. Read more: Cuming, Rosemary S., Eva M. Abarca, Sue Duran, Anne A. Wooldridge, Allison J. Stewart, William Ravis, R. Jayachandra Babu, Yuh-Jing Lin, and Terri Hathcock. "Development of a Sustained-Release Voriconazole-Containing Thermogel for Subconjunctival Injection in Horses Subconjunctival Voriconazole-Thermogel." Investigative Ophthalmology & Visual Science 58, no. 5 (2017): 2746-2754. http://iovs.arvojournals.org/article.aspx?articleid=2629760

“Abstract: Purpose: To determine in vitro release profiles, transcorneal permeation, and ocular injection characteristics of a voriconazole-containing thermogel suitable for injection into the subconjunctival space (SCS). Methods: In vitro release rate of voriconazole (0.3% and 1.5%) from poly (DL-lactide-co-glycolide-b-ethylene glycol-b-DL-lactide-co-glycolide) (PLGA-PEG-PLGA) thermogel was determined for 28 days. A Franz cell diffusion chamber was used to evaluate equine transcorneal and transscleral permeation of voriconazole (1.5% topical solution, 0.3% and 1.5% voriconazole-thermogel) for 24 hours. Antifungal activity of voriconazole released from the 1.5% voriconazole-thermogel was determined via the agar disk diffusion method. Ex vivo equine eyes were injected with liquid voriconazole-thermogel (4°C). Distension of the SCS was assessed ultrasonographically and macroscopically. SCS voriconazole-thermogel injections were performed in a horse 1 week and 2 hours before euthanasia and histopathologic analysis of ocular tissues performed. Results: Voriconazole was released from the PLGA-PEG-PLGA thermogel for more than 21 days in all groups. Release followed first-order kinetics. Voriconazole diffused through the cornea and sclera in all groups. Permeation was greater through the sclerae than corneas. Voriconazole released from the 1.5% voriconazole-thermogel showed antifungal activity in vitro. Voriconazole-thermogel was easily able to be injected into the dorsal SCS where it formed a discrete gel deposit. Voriconazole-thermogel was easily injected in vivo and did not induce any adverse reactions. Conclusions: Voriconazole-containing thermogels have potential application in treatment of keratomycosis. Further research is required to evaluate their performance in vivo.”


PolySciTech PLGA-NH2 used in study on nanoparticle biotransport: Nanoparticle transport explained using a kitten and a football game.

Tuesday, June 6, 2017, 11:16 AM ET



Nanoparticles are small… really small. To put it in perspective, a typical human cell ranges in size from 30-100 um in diameter. Nanoparticles range in size from 1 um down to 0.001 um (0.1 um being common) which means that a typical cell is between 300-1000 times the size of a nanoparticle. To put that in perspective, if a nanoparticle was the size of a kitten (~30 cm) then a human cell would close to the size of a football field (~90-100 M). One important question in science is how to get the kitten onto the football field… er… I mean… how to get the nanoparticle into the cell. This is important because nanoparticles can be loaded with medicines that have a variety of therapeutic effects which can be leveraged only if the nano-kitten can make it onto the cellular football field to make the game-winning kick. There’s two basic ways for either to happen. 1. Active targeting: For our metaphor we’ll assume nano-kitty has a game-day ticket which he politely presents at the front gate for entrance. Similarly, nanoparticles can be specifically conjugated to a specific signal molecule that has the right configuration to allow the nanoparticle access through the cellular membrane by accepted channels. (or) 2. Passive-targeting: This simply relies on the really small nano-kitten simply squeezing through a fence and slipping onto the football field ‘unseen’ due to its small size. Similarly, nanoparticles can sometimes enter cells simply because of their small size. A recent study using PST polymers focused on examining the processes at play in passive-targeting. In addition to final-products used directly for research, PolySciTech (www.polyscitech.com) provides a wide array of intermediates which can be used as precursors for making the final materials. For example, amine-endcap activated PLGA-NH2 has the capability to be chemically conjugated to a wide variety of molecules using common laboratory techniques such as carbodiimide-type conjugation between the PLGA-amine and a NHS-activated carboxylic acid on the other molecule. Recently, researchers at Johns Hopkins University utilized PLGA-NH2 (PolyVivo Cat# AI051) as part of an investigation into nanoparticle transport into living cells. They took the PLGA-NH2 and conjugated on a ‘caged’ rhodamine dye that did not fluoresce until it was prepared to do so by exposure to UV-light. This clever technique allowed the researchers to encapsulate the dye completely within the nanoparticles and precisely track and characterize the nanoparticles during cellular uptake studies. This research holds promise to improve nanotherapeutic formulations for treating a wide-variety of diseases. Read more: Schuster, Benjamin S., Daniel B. Allan, Joshua C. Kays, Justin Hanes, and Robert L. Leheny. "Photoactivatable fluorescent probes reveal heterogeneous nanoparticle permeation through biological gels at multiple scales." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S0168365917306302

“Abstract: Diffusion through biological gels is crucial for effective drug delivery using nanoparticles. Here, we demonstrate a new method to measure diffusivity over a large range of length scales – from tens of nanometers to tens of micrometers – using photoactivatable fluorescent nanoparticle probes. We have applied this method to investigate the length-scale dependent mobility of nanoparticles in fibrin gels and in sputum from patients with cystic fibrosis (CF). Nanoparticles composed of poly(lactic-co-glycolic acid), with polyethylene glycol coatings to resist bioadhesion, were internally labeled with caged rhodamine to make the particles photoactivatable. We activated particles within a region of sample using brief, targeted exposure to UV light, uncaging the rhodamine and causing the particles in that region to become fluorescent. We imaged the subsequent spatiotemporal evolution in fluorescence intensity and observed the collective particle diffusion over tens of minutes and tens of micrometers. We also performed complementary multiple particle tracking experiments on the same particles, extending significantly the range over which particle motion and its heterogeneity can be observed. In fibrin gels, both methods showed an immobile fraction of particles and a mobile fraction that diffused over all measured length scales. In the CF sputum, particle diffusion was spatially heterogeneous and locally anisotropic but nevertheless typically led to unbounded transport extending tens of micrometers within tens of minutes. These findings provide insight into the mesoscale architecture of these gels and its role in setting their permeability on physiologically relevant length scales, pointing toward strategies for improving nanoparticle drug delivery.Keywords: Photoactivation; Fibrin; Cystic fibrosis; Nanoparticle; Drug delivery; Particle tracking; FRAP; Fluorescence microscopy; Diffusion. (Dye Conjugation protocol): Caged rhodamine-NHS ester and PLGA-NH2 were conjugated through formation of an amide bond. (Conjugating the dye to polymer in this way, rather than encapsulating the dye in the particles, reduces the likelihood of free dye being released.) Briefly, 90 mg of PLGA-NH2 was added to 5 mg of caged rhodamine-NHS ester, leading to a slight molar excess of dye compared to PLGA, 1.23:1, and put under vacuum for 1 h. The mixture was then flushed with nitrogen gas, dissolved in 500 μl of anhydrous dichloromethane (DCM), and reacted for 12 h at room temperature under nitrogen gas. Additional DCM was added as needed to facilitate transfer into 10 ml of − 20 °C diethyl ether to precipitate the product. The PLGA, now conjugated with the caged rhodamine, was washed twice in cold ether by centrifugation. Excess ether was decanted off and the final product, the purified PLGA-caged rhodamine, was placed in a lyophilizer (FreeZone 4.5 Plus; Labconco) for 12 h. The dried product was stored at − 20 °C in a shielded container to prevent exposure to incident UV light. It is important to note that the amide bond is formed between the amine end-cap of the PLGA and the succinimidyl (NHS) ester on the rhodamine; that is, the dye itself and not the ortho-nitroveratryloxycarbonyl (NVOC) cage is directly conjugated to PLGA. Thus, when the photolytic reaction occurs upon exposure to UV light, only the caging group is cleaved, and free dye is not released”


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

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