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

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

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

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.

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

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

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

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”