Monthly Archives: January 2016

PLGA-PEG investigated for Chrysin delivery against gastric cancer

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers including PEG-PLGA. Chrysin is a hydrophobic flavonoid with potent anti-inflammatory and anti-oxidant properties. However, when taken orally by humans, it has negligible bioavailability due to extensive degradation. Recently, tests involving delivery of Chrysin using PEG-PLGA have shown that it has increased potency when delivered using this system which results in down-regulation of marker genes involved with gastric cancer. Read more: Mohammadian, Farideh, Yones Pilehvar-Soltanahmadi, Mohsen Mofarrah, Mehdi Dastani-Habashi, and Nosratollah Zarghami. “Down regulation of miR-18a, miR-21 and miR-221 genes in gastric cancer cell line by chrysin-loaded PLGA-PEG nanoparticles.” Artificial Cells, Nanomedicine, and Biotechnology (2016): 1-7. http://www.tandfonline.com/doi/abs/10.3109/21691401.2015.1129615

“Abstract: Chrysin were well-documented as having significant biological roles particularly cancer chemo-preventive activity. However, the poor water solubility of chrysin limited their bioavailability and biomedical applications. In this study, we encapsulate the chrysin into PLGA-PEG nanoparticles for local treatment. In regard to the amount of the drug load, IC50 was significant decreased in nanocapsulated chrysin in comparison with free chrysin. This was confirmed through decrease of miR-18a, miR-21, and miR-221 genes expression by real-time PCR. The results demonstrated that PLGA-PEG-chrysin complexes can be more effective than free chrysin. Therefore, PLGA-PEG can be a better nanocarrier for this kind of hydrophobic flavonoid.”

Syringopicroside and hydroxytyrosol delivery by PEG-PLGA polymers investigated for prevention of liver damage

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of PLGA and related block copolymers. Recently a paper has come out using mPEG-PLGA to delivery anti-oxidant drugs syringopicroside and hydroxytyrosol. Read more: Guan, Qingxia, Shuang Sun, Xiuyan Li, Shaowa Lv, Ting Xu, Jialin Sun, Wenjing Feng, Liang Zhang, and Yongji Li. “Preparation, in vitro and in vivo evaluation of mPEG-PLGA nanoparticles co-loaded with syringopicroside and hydroxytyrosol.” Journal of Materials Science: Materials in Medicine 27, no. 2 (2016): 1-13. http://link.springer.com/article/10.1007/s10856-015-5641-x

“Abstract: This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was −24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.”

Article highlights use of PEG-PLGA for antibiotic delivery to bone as osteomyelitis treatment

PolySciTech division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable block copolymers including PEG-PLGA type polymers. These have the benefit of being easily formulated into microparticles by simple emulsion techniques (effectively rapidly stirring the organic solvent dissolved polymer into a water bath). One useful aspect of these polymers is that the hydrophilic PEG-chain of the block copolymer naturally turns to the exterior of the microparticle upon emulsion. PEG has a very useful feature in that, due to its hydrodynamic structure, it is highly bio-inert and prevents protein absorption. This allows pegylated particles to resist immune system responses such as attack by macrophages and other forms of particle clearance that affect non-pegylated microparticles. In a recent study, a group for the University of Pavia in Italy generated a series of pegylated microparticles and investigated their application for delivery of gentamicin to bone structures to prevent postoperative orthopedic infections such as osteomyelitis. Read more: Dorati, Rossella, Antonella DeTrizio, Ida Genta, Pietro Grisoli, Alessia Merelli, Corrado Tomasi, and Bice Conti. “An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery.” Materials Science and Engineering: C 58 (2016): 909-917. http://www.sciencedirect.com/science/article/pii/S0928493115303799

“Abstract: The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1–97.5%), and span values of particle size distribution (1.03–1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone. Keywords: DOE; Gentamicin; Osteomyelitis; Microspheres; Polylactide-co-glycolide; Polyethyleneglycol; Bone delivery. Highlights: To get a more effective therapy for the prevention and treatment of osteomyelitis. To exploit the local delivery of gentamicin to bone by a biodegradable microparticulate drug delivery system. Polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microsphere as biodegradable drug delivery system. Process variables affecting microspheres properties are investigated. Design Of Experiment (DOE) screening design as approach to scale up manufacturing step.”

Review article highlights usage of PEG-PLGA type polymers for drug delivery

PolySciTech division of Akina, Inc. (www.polyscitech.com) provides a wide array of biodegradable block copolymers. Recently, an excellent review article came out which covers the use of these types of polymers for drug delivery applications. This article touches on several applications of PEG-PLGA type drug delivery including delivery strategies for drugs such as ICU 189150, doxorubicin, paclitaxel, docetaxel, etoposide, rapamycin,17-AAG, bicalutamide, embelin, suberoylanilide hydroxamic acid, β-lapachone, pifithrin, sagopilone, and thiocoraline. There is also information regarding clinical formulations which have been tried previously in clinical trials including Genexol and Oncogel. Genexol is an mPEG-PLA based formulation with block sizes of 2000Da mPEG and 1750Da PLA. The most similar Polyvivo product to this one would be Cat# AK069. Oncogel is based off of Regel which is a PLGA-PEG-PLGA with overall molecular weight of 4200Da and a ratio of LA:GA of 3:1. The most similar PolyVivo product to this one would be Cat# AK091. Read more: Cho, Hyunah, Jieming Gao, and Glen S. Kwon. “PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol–gels for drug delivery.” Journal of Controlled Release (2015). http://www.sciencedirect.com/science/article/pii/S0168365915302674

“Abstract: Poly(ethylene glycol)-block-poly(D,L-lactic acid) (PEG-b-PLA) micelles and poly(D,L-lactic-co-glycolic acid)-block-polyethylene glycol)-block-poly(D,L-lactic-co-glycolic acid) (PLGA-b-PEG-b-PLGA) sol–gels have been extensively researched for systemic and localized drug delivery applications, respectively, and they have both progressed into humans for paclitaxel, an important yet poorly water-soluble chemotherapeutic agent. In this review article, preclinical and clinical research on PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol–gels that has focused on paclitaxel will be updated, and recent research on other poorly water-soluble anticancer agents and delivery of drug combinations (i.e. multi-drug delivery) that seeks synergistic anticancer efficacy will be summarized. PEG-b-PLA micelles are a first-generation platform for the systemic multi-delivery of poorly water soluble anticancer agents. PLGA-b-PEG-b-PLGA sol–gels are a first-generation platform for the localized multi-drug delivery of water-soluble and/or poorly water-soluble anticancer agents. In summary, PEG-b-PLA micelles and PLGA-b-PEG-b-PLGA sol–gels may safely enable pre-clinical evaluation and clinical translation of poorly water-soluble anticancer agents, especially for promising, rapidly emerging anticancer combinations. Keywords: Block copolymer; Controlled release; Drug combination; Drug solubilization; Hydrogels; Polymeric micelles; Prodrugs”

PLGA from PolySciTech used for nanoparticle based docetaxel delivery system

PolySciTech Division of Akina, Inc (www.polyscitech.com) provides a wide array of biodegradable polymers including PLGA. Recently, PLGA (Cat# AP082) from PolySciTech was used, along with HS15 nonionic surfactant to generate nanoparticles loaded with docetaxel. These nanoparticles (~169 nm in size, about 250 times smaller than a typical 40 um human tissue cell) possessed good drug distribution throughout and other properties which indicated that they would have good capabilities for drug delivery. Read more: Cho, Hyun-Jong, Ju-Hwan Park, Dae-Duk Kim, and In-Soo Yoon. “Poly (lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.” Journal of Nanoscience and Nanotechnology 16, no. 2 (2016): 1433-1436. http://www.ingentaconnect.com/content/asp/jnn/2016/00000016/00000002/art00029

“Abstract:Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lacticco-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.”