Monthly Archives: June 2016

PLGA-Rhodamine from PolySciTech used for development of drug-delivery system as potential treatment of Peritoneal Mesothelioma

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including fluorescently conjugated PLGA’s used for nanoparticle tracking. Recently, researchers used Poly(lactide-co-glycolide)-Rhodamine B (PolyVivo# AV011) from PolySciTech as part of a nanoparticle tracking system in the development of paclitaxel loaded nanoparticles for targeted drug delivery to mesothelioma. This research has the potential to treat a deadly disease. Read more here: Liu, Rong, Aaron H. Colby, Denis Gilmore, Morgan Schulz, Jialiu Zeng, Robert F. Padera, Orian Shirihai, Mark W. Grinstaff, and Yolonda L. Colson. “Nanoparticle tumor localization, disruption of autophagosomal trafficking, and prolonged drug delivery improve survival in peritoneal mesothelioma.” Biomaterials 102 (2016): 175-186. http://www.sciencedirect.com/science/article/pii/S014296121630285X

“Abstract: The treatment outcomes for malignant peritoneal mesothelioma are poor and associated with high co-morbidities due to suboptimal drug delivery. Thus, there is an unmet need for new approaches that concentrate drug at the tumor for a prolonged period of time yielding enhanced antitumor efficacy and improved metrics of treatment success. A paclitaxel-loaded pH-responsive expansile nanoparticle (PTX-eNP) system is described that addresses two unique challenges to improve the outcomes for peritoneal mesothelioma. First, following intraperitoneal administration, eNPs rapidly and specifically localize to tumors. The rate of eNP uptake by tumors is an order of magnitude faster than the rate of uptake in non-malignant cells; and, subsequent accumulation in autophagosomes and disruption of autophagosomal trafficking leads to prolonged intracellular retention of eNPs. The net effect of these combined mechanisms manifests as rapid localization to intraperitoneal tumors within 4 h of injection and persistent intratumoral retention for >14 days. Second, the high tumor-specificity of PTX-eNPs leads to delivery of greater than 100 times higher concentrations of drug in tumors compared to PTX alone and this is maintained for at least seven days following administration. As a result, overall survival of animals with established mesothelioma more than doubled when animals were treated with multiple doses of PTX-eNPs compared to equivalent dosing with PTX or non-responsive PTX-loaded nanoparticles. Keywords: Mesothelioma; Nanoparticle; Drug delivery; Paclitaxel; Autophagosome; Tumor localization”

PLCL from PolySciTech used as part of nanoparticle carrier for SN-38 and investigated for chemotherapy

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including poly(lactide-co-caprolactone) PLCL. Recently, PLCL from Akina, Inc. (PolyVivo AP103) was used to generate a poloxamer-PLCL nanoparticle which was loaded with the novel antineoplastic drug SN-38 which acts to prevent cancer from growing new cells. These nanoparticles were then investigated to determine their applicability to biological systems. This research holds promise for development of novel chemotherapeutic strategies to treat cancer. Read more: Koliqi, Rozafa, Simona Dimchevska, Nikola Geskovski, Gjorgji Petruševski, Marina Chacorovska, Biljana Pejova, Delyan R Hristov, Sonja Ugarkovic, and Katerina Goracinova. “PEO-PPO-PEO/Poly (DL-lactide-co-caprolactone) Nanoparticles as Carriers for SN-38: Design, Optimization and Nano-Bio Interface Interactions.” Current drug delivery 13, no. 3 (2016): 339-352. http://www.ingentaconnect.com/contentone/ben/cdd/2016/00000013/00000003/art00008

“Abstract: Encapsulation of extremely hydrophobic substances such as SN-38 into nanoparticles, is a promising approach to solve the solubility issue and enable drug administration. Moreover, nanocarriers’ tumor homing behavior, targeted and controlled release at the site of action will optimize therapeutic potency and decrease toxicity of the incorporated drug substance. However, the enormous drug hydrophobicity might limit the capacity for encapsulation as the premature drug precipitation will contribute to fast free drug crystal growth, low drug incorporation and huge waste of the active material. In this article we defined the optimal region for manufacturing of SN-38 loaded PEO-PPO-PEO/P(DL)LCL nanoparticles (NPs) with high efficacy of encapsulation, suitable particle size and different surface properties, using D-optimal design and nanoprecipitation as production method. Further we made an approach to investigate the interactions with macromolecules at the nano-bio interface which are predetermined by the physico-chemical and surface properties of the NPs, and are important determinants for the biological identity of the nanoparticles, the potential for evasion of the physiological barriers and the efficacy of localization at the site of action. Here we present in depth analysis of the behavior of two types of nanoparticles with different surface properties through structured protein interaction and bioreactivity experiments in order to presuppose NP performance and toxicological profile in biological environment. Keywords: D-optimal design; P(DL)LCL; PEO-PPO-PEO; Polymeric nanoparticles; SN-38; nano-bio interface; protein corona”

PEG-PLA from PolySciTech used as part of development of hypoxia targeted pancreatic cancer drug delivery system

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers. Recently, researchers at North Dakota State University purchased mPEG-PLLA (2000-5000Da) (PolyVivo AK004). They used this well characterized polymer as a control to generate ‘typical’ polymersomes loaded with gemcitabine (a nucleoside analog) and erlotinib (a tyrosine kinase) for pancreatic cancer treatment. They compared this against ‘responsive’ polymersomes made with their developed hypoxia-targeted system. Read more: Kulkarni, Prajakta, Manas K. Haldar, Seungyong You, Yongki Choi, and Sanku Mallik. “Hypoxia-responsive polymersomes for drug delivery to hypoxic pancreatic cancer cells.” Biomacromolecules (2016). http://pubs.acs.org/doi/abs/10.1021/acs.biomac.6b00350

“Abstract: Hypoxia in the tumors contributes to overall tumor progression by assisting in epithelial-to-mesenchymal transition, angiogenesis, and metastasis of cancer. In this study, we have synthesized a hypoxia-responsive, di-block copolymer polylactic acid-azobenzene-polyethylene glycol, which self-assembles to form polymersomes in an aqueous medium. The polymersomes were stable under normoxic conditions. However, under hypoxia, 90% of the encapsulated dye was released in 50 minutes. The polymersomes encapsulated the combination of anticancer drugs gemcitabine and erlotinib with entrapment efficiency of 40% and 28% respectively. We used the three-dimensional spheroid cultures of the pancreatic cancer cells BxPC-3 to demonstrate hypoxia-mediated release of the drugs from the polymersomes. The vesicles were non-toxic. However, a significant decrease in cell viability was observed in hypoxic spheroidal cultures of BxPC-3 cells in the presence of drug encapsulated polymersomes. These polymersomes have the potential for further applications in imaging and treatment of hypoxic tumors.”

PolySciTech Poly(aspartic acid) used in development of SiRNA delivery

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including poly(aspartic acid). Recently, this material was used in part of development of SiRNA delivery system. Read more: Hattori, Yoshiyuki, Yuki Yoshiike, Takuto Kikuchi, Natsumi Yamamoto, Kei-ichi Ozaki, and Hiraku Onishi. “Evaluation of the injection route of an anionic polymer for small interfering RNA delivery into the liver by sequential injection of anionic polymer and cationic lipoplex of small interfering RNA.” Journal of Drug Delivery Science and Technology (2016). http://www.sciencedirect.com/science/article/pii/S1773224716301812

“Abstract: Previously, we developed a novel small interfering RNA (siRNA) transfer method for the liver by sequential intravenous injection of an anionic polymer and cationic liposome/siRNA complex (cationic lipoplex). In this study, we examined the effects of the type of anionic polymer and injection route of the anionic polymer on the biodistribution of siRNA after sequential injection of anionic polymer and cationic lipoplexes. When cationic lipoplexes were injected intravenously into mice, siRNA largely accumulated in the lungs. In contrast, sequential injection of cationic lipoplex after intravenous injection of 1 mg chondroitin sulfate C and A (CS-C and CS-A) or polyaspartic acid decreased the accumulation of siRNA in the lungs and increased it in the liver, compared with injection of cationic lipoplex. Regarding the injection route of the anionic polymer, intramuscular, intraperitoneal, or subcutaneous injection of 10 mg CS-C before intravenous injection of cationic lipoplex resulted in siRNA accumulation mainly in the liver. Furthermore, the injection of cationic lipoplex of apolipoprotein B (ApoB) siRNA after intravenous or intramuscular injection of CS-C could suppress ApoB mRNA levels in the liver. Sequential injection of CS-C plus cationic lipoplex could deliver siRNA efficiently into the liver regardless of the injection route of CS-C. Keywords: siRNA delivery; liposome; chondroitin sulfate; liver; gene silencing”

Updated Technical and Safety Information on PolySciTech website

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers and related research products. As we continue to grow, PolySciTech is working towards prioritizing providing helpful product technical data for customers. Outside of typical certificate of analysis data (HNMR, FTIR, GPC) we also have supplemental data for many of our products available on our product information page (https://akinainc.com/polyscitech/products/polyvivo/info.php). Recently, Akina has procured a state-of-the-art modulated DSC (Q2000 TA instruments). We are updating the available DSC data on our website collected previously with a TA-2010 with modulated DSC data. Additionally, we are in the process of establishing intrinsic viscosity (25C dichloromethane) for our products with a micro-visc meter and this will soon be available on the site. In addition to technical data, the MSDS files available have been updated to the globally harmonized SDS version which is available online for products as well (https://akinainc.com/polyscitech/products/polyvivo/SDS.php). As always, links to research papers and published data for our products is available here (https://akinainc.com/polyscitech/products/polyvivo/referenced_by.php). Recently, we broke over 100 published manuscripts listing the use of our products in their research and counting.

PLGA purchased from PolySciTech used for development of composite polymer-iron nanoparticles for EPR-independent delivery system as a cancer treatment

PolySciTech Division of Akina, inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Recently, PLGA (85:15) 150kDa (PolyVivo AP020) purchased from PolySciTech was utilized by researchers to generate a composite nanoparticle containing iron oxide. They found that the flow of these particles could be controlled in-vivo by using magnetic fields to focus their concentration at the tumor site. Under certain conditions, leaky tumor vasculature and greater vascularization can lead to an effect referred to as Enhanced Permeation and Retention (EPR). However, this does not work for all tumors. This method of nanoparticle delivery relies on magnetism rather than EPR and holds promise for cancers where the tumor is poorly vascularized and EPR effect is little. Read more about this exciting research here: Park, Jinho, Naveen R. Kadasala, Sara A. Abouelmagd, Mark A. Castanares, David S. Collins, Alexander Wei, and Yoon Yeo. “Polymer–iron oxide composite nanoparticles for EPR-independent drug delivery.” Biomaterials (2016). http://www.sciencedirect.com/science/article/pii/S0142961216302617

“Abstract: Nanoparticle (NP)-based approaches to cancer drug delivery are challenged by the heterogeneity of the enhanced permeability and retention (EPR) effect in tumors and the premature attrition of payload from drug carriers during circulation. Here we show that such challenges can be overcome by a magnetophoretic approach to accelerate NP delivery to tumors. Payload-bearing poly(lactic-co-glycolic acid) NPs were converted into polymer–iron-oxide nanocomposites (PINCs) by attaching colloidal Fe3O4 onto the surface, via a simple surface modification method using dopamine polymerization. PINCs formed stable dispersions in serum-supplemented medium and responded quickly to magnetic field gradients above 1 kG/cm. Under the field gradients, PINCs were rapidly transported across physical barriers and into cells and captured under flow conditions similar to those encountered in postcapillary venules, increasing the local concentration by nearly three orders of magnitude. In vivo magnetophoretic delivery enabled PINCs to accumulate in poorly vascularized subcutaneous SKOV3 xenografts that did not support the EPR effect. In vivo magnetic resonance imaging, ex vivo fluorescence imaging, and tissue histology all confirmed that the uptake of PINCs was higher in tumors exposed to magnetic field gradients, relative to negative controls. Keywords: Polymer–iron oxide nanocomposite; Magnetic drug delivery; Polymeric nanoparticles; Polydopamine; In vivo delivery”

PEG precursor from PolySciTech used as part of folate-mediated delivery system development for brain cancer treatment

PolySciTech Division of Akina, Inc. (www.polyscitech.com) provides a wide array of polymers including heterobifunctional PEG precursors. Recently PolyVivo AE003 (Folate-PEG-COOH (3000Da)) was used by researchers at University of Puerto Rico to develop a folate-mediated delivery system for targeted application of cytochrome c, a protein that initiates apoptosis (cell-death). This research holds promise for enhanced chemotherapy techniques to kill off tumor cells while minimalizing toxic side-effects against normal cells. Read more: Morales-Cruz, Moraima, Alejandra Cruz-Montañez, Cindy M. Figueroa, Tania Gonzalez-Robles, Josue Davila, Mikhail Inyushin, Sergio A. Loza-Rosas et al. “Combining stimulus-triggered release and active targeting strategies improves cytotoxicity of cytochrome c nanoparticles in tumor cells.” Molecular Pharmaceutics (2016). http://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.6b00461

“Proteins often possess highly specific biological activities that make them potential therapeutics, but their physical and chemical instabilities during formulation, storage, and delivery have limited their medical use. Therefore, engineering of nano-sized vehicles to stabilize protein therapeutics and to allow for targeted treatment of complex diseases, such as cancer, is of considerable interest. A micelle-like nanoparticle (NP) was designed for both, tumor targeting and stimulus-triggered release of the apoptotic protein cytochrome c (Cyt c). This system is composed of a Cyt c NP stabilized by a folate-receptor targeting amphiphilic copolymer (FA-PEG-PLGA) attached to Cyt c through a redox-sensitive bond. FA-PEG-PLGA-S-S-Cyt c NPs exhibited excellent stability under extracellular physiological conditions, whereas once in the intracellular reducing environment, Cyt c was released from the conjugate. Under the same conditions, the folate-decorated NP reduced folate receptor positive HeLa cell viability to 20% while the same complex without FA only reduced it to 80%.  Confocal microscopy showed that the FA-PEG-PLGA-S-S-Cyt c NPs were internalized by HeLa cells and were capable of endosomal escape.  The specificity of the folate receptor-mediated internalization was confirmed by the lack of uptake by two folate receptor deficient cell lines: A549 and NIH-3T3. Finally, the potential as anti-tumor therapy of our folate-decorated Cyt c-based NPs was confirmed with an in vivo brain tumor model. In conclusion, we were able to create a stable, selective, and smart nanosized Cyt c delivery system.”

Thermogelling PLGA-PEG-PLGA from PolySciTech used for delivery of paclitaxel, rapamycin, and LS301 as part of ovarian cancer theranostic research.

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including thermogels such as PLGA-PEG-PLGA. One of the uses for this type of polymer is to provide for injectable delivery of medicines. Because the polymer gels and entraps the pharmaceuticals inside, it allows for localized delivery of the drug over a period of time. Recently, researchers have utilized this polymer to create a co-formulation with three chemotherapeutic and theranostic agents (paclitaxel, rapamycin, and LS301). They injected this in a mouse model and tracked its effect against ovarian cancer cells. Read more: McKenzie, Matthew, David Betts, Amy Suh, Kathryn Bui, Rui Tang, Kexian Liang, Samuel Achilefu, Glen S. Kwon, and Hyunah Cho. “Proof-of-Concept of Polymeric Sol-Gels in Multi-Drug Delivery and Intraoperative Image-Guided Surgery for Peritoneal Ovarian Cancer.” Pharmaceutical Research (2016): 1-9. http://link.springer.com/article/10.1007/s11095-016-1968-3

“Abstract: Purpose: The purpose of this study is to investigate a sol–gel transition property and content release profiles for thermosensitive poly-(D,L-lactide-co-glycolide)-block-poly-(ethylene glycol)-block-poly-(D,L-lactide-co-glycolide) (PLGA-b-PEG-b-PLGA) hydrogels carrying paclitaxel, rapamycin, and LS301, and to present a proof-of-concept that PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, called TheranoGel, exhibit excellent theranostic activity in peritoneal ES-2-luc ovarian cancer xenograft mice. Methods: Thermosensitive PLGA-b-PEG-b-PLGA hydrogels carrying paclitaxel, rapamycin, and LS301, individually or in combination, were prepared via a lyophilization method, characterized with content release kinetics, and assessed with theranostic activity in ES-2-luc xenograft mice. Results: A thermosensitive PLGA-b-PEG-b-PLGA sol–gel system was able to entrain 3 poorly water-soluble payloads, paclitaxel, rapamycin, and LS301 (TheranoGel). TheranoGel made a sol-to-gel transition at 37°C and slowly released 3 drugs at a simultaneous release rate in response to the physical dissociation of hydrogels in vitro. TheranoGel enabled loco-regional delivery of multi-drugs by forming a gel-depot in the peritoneal cavity of ES-2-luc xenograft mice. An intraperitoneal (IP) administration of TheranoGel resulted in excellent therapeutic and diagnostic activities, leading to the improved peritoneal surgery in ES-2-luc xenograft mice. Conclusions: TheranoGel prepared via a facile lyophiliation method enabled successful IP delivery of multi-drugs and exhibited excellent theranostic activity in vivo. KEY WORDS: hydrogels intraperitoneal ovarian cancer theranostics thermosensitive”

Fluorescently labeled PLGA from PolySciTech used as part of self-assembled PLGA microparticle system research

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers for research usage. This includes fluorescently conjugated polymers such as PLGA conjugated to flamma-fluor dyes. Recently, researchers used Fluorescent PolyVivo AV008 (PLGA-FPR648, reference named in paper as related material PLGA-CY5) for development of a self-assembled microparticle system. Read more: Yeredla, Nitish, Taisuke Kojima, Yi Yang, Shuichi Takayama, and Mathumai Kanapathipillai. “Aqueous Two Phase System Assisted Self-Assembled PLGA Microparticles.” Scientific Reports 6 (2016): 27736. http://www.nature.com/articles/srep27736

“Abstract: Here, we produce poly(lactide-co-glycolide) (PLGA) based microparticles with varying morphologies, and temperature responsive properties utilizing a Pluronic F127/dextran aqueous two-phase system (ATPS) assisted self-assembly. The PLGA polymer, when emulsified in Pluronic F127/dextran ATPS, forms unique microparticle structures due to ATPS guided-self assembly. Depending on the PLGA concentration, the particles either formed a core-shell or a composite microparticle structure. The microparticles facilitate the simultaneous incorporation of both hydrophobic and hydrophilic molecules, due to their amphiphilic macromolecule composition. Further, due to the lower critical solution temperature (LCST) properties of Pluronic F127, the particles exhibit temperature responsiveness. The ATPS based microparticle formation demonstrated in this study, serves as a novel platform for PLGA/polymer based tunable micro/nano particle and polymersome development. The unique properties may be useful in applications such as theranostics, synthesis of complex structure particles, bioreaction/mineralization at the two-phase interface, and bioseparations.”

PLGA-Cholesterol from PolySciTech investigated for targeted nanoparticle therapy of laryngeal cancer

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA derivatives such as PLGA with a cholesterol endcap. Cholesterol has been found as an important molecule involved in endocytosis (cellular uptake) as well as, more specifically for cancer, it is used for enhanced proliferation and metastasis. Researchers at Seoul National and Kangwon National universities in Korea recently encapsulated curcumin in PLGA-cholesterol from PolySciTech forming drug loaded nanoparticles. They found, by flow cytometry, confocal microscopy techniques, and mouse-model studies that these nanoparticles are preferentially up-taken into cancer cells (Human Laryngeal Carcinoma) over typical PLGA nanoparticles. This research holds promise for improved targeted delivery of chemotherapeutic agents to cancer sites for higher efficacy and lower side-effects from these types of treatments. Read more here: Lee, Jeong-Jun, Song Yi Lee, Ju-Hwan Park, Dae-Duk Kim, and Hyun-Jong Cho. “Cholesterol-modified poly (lactide-co-glycolide) nanoparticles for tumor-targeted drug delivery.” International Journal of Pharmaceutics (2016). http://www.sciencedirect.com/science/article/pii/S0378517316304847

“Abstract: Poly(lactide-co-glycolide)-cholesterol (PLGA-C)-based nanoparticles (NPs) were developed for tumor-targeted delivery of curcumin (CUR). PLGA-C/CUR NPs with ∼200 nm mean diameter, narrow size distribution, and neutral zeta potential were fabricated by modified emulsification-solvent evaporation method. The existence of cholesterol moiety in PLGA-C copolymer was confirmed by proton nuclear magnetic resonance (1H NMR) analysis. In vitro stability of developed NPs after 24 h incubation was confirmed in phosphate buffered saline (PBS) and serum media. Sustained (∼6 days) and pH-responsive drug release profiles from PLGA-C NPs were presented. Blank PLGA and PLGA-C NPs exhibited negligible cytotoxicity in Hep-2 (human laryngeal carcinoma) cells in the tested concentration range. According to the results of flow cytometry and confocal laser scanning microscopy (CLSM) studies, PLGA-C NPs presented an improved cellular accumulation efficiency, compared to PLGA NPs, in Hep-2 cells. Enhanced in vivo tumor targetability of PLGA-C NPs, compared to PLGA NPs, in Hep-2 tumor-xenografted mouse model was also verified by real-time near- infrared fluorescence (NIRF) imaging study. Developed PLGA-C NPs may be a candidate of efficient and biocompatible nanosystems for tumor-targeted drug delivery and cancer imaging. Keywords: Cancer; Cholesterol; Curcumin; Endocytosis; Nanoparticle”