Polymeric micelles based on poly(ethylene glycol) block poly(racemic amino acids) hybrid polypeptides: conformation-facilitated drug-loading behavior and potential application as effective anticancer drug carriers

Abstract

Abstract:In this work, racemic hybrid polypeptides poly(ethylene glycol) (PEG)-bpoly(racemic-leucine) (PRL) copolymers with different leucine residues have been synthesized and characterized. Using docetaxel as a model molecule, the high drug-loaded spherical micelles based on PEG-PRL were prepared successfully using dialysis, with a tunable particle size from 170 nm to 250 nm obtained by changing the length of the hydrophobic blocks. Facilitated drugloading behavior (higher drug-loading ability and easier drug-loading process) of PEG-PRL compared with their corresponding levo forms (PEG-b-poly[levo leucine]) was observed and clarified for the first time. With this facilitation, the highest drug-loading content and efficiency of PEG-PRL micelles can achieve 11.2% ± 0.4% and 67.2% ± 2.4%, respectively. All drugloaded PEG-PRL micelles exhibit a similar release behavior with a sustained release up to 72 hours. The PEG-PRL was shown to be nontoxic against MCF-7 and human umbilical vein endothelial cells up to a concentration of 100 μg/mL, displaying a good biocompatibility. Also, the docetaxel-loaded PEG-PRL micelles were more toxic than the free drug against MCF-7 human breast cancer cells -both dose and time dependent. Therefore, these high docetaxel-loaded micelles based on racemic hybrid polypeptides appear to be a novel promising nanomedicine for anticancer therapy.

Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cellsin vitro

“…The quantity of ALA dissolved in the collected media was analyzed by HPLC. All data were evaluated from the determination conducted at least in triplicates (Gu et al, 2012;Zhang et al, 2012).…”

“…As a powerful active ingredients-loading vehicle, the materials applied should be verified to be exceedingly biocompatible to humans. Consequently, the in vitro cytotoxicity of the ALA-NLC was investigated with HaCaT cell line to determine the biocompatibility (Gu et al, 2012). The cell viability of HaCaT cells incubated with ALA-NLC aqueous dispersion was assessed using the MTT assay to study the possible applicability.…”

In vitro evaluation of anticancer nanomedicines based on doxorubicin and amphiphilic Y-shaped copolymers

“…The obtained product was further washed, twice, with diethyl ether, and dried under vacuum at room temperature for 24 hours (yield: 97%). 1 Synthesis of amphiphilic Y-shaped copolymers (mPEG-P(LA-co-GA) 2 …”

“…1,2 Amphiphilic copolymers have been widely studied as economic and versatile nanoscale drug carriers, due to their typical diameter of several tens of nanometers and relatively narrow size distribution. [3][4][5] The unique compositions, molecular geometry, and physicochemical properties of the amphiphilic copolymers enable them to aggregate into nanoparticles with various morphologies in aqueous medium, such as micelles [6][7][8][9] and vesicles.…”

“…In brief, mPEG-(OH) 2 was dissolved in freshly distilled toluene and azeotropically distilled at 120°C to remove micro-amounts of water. Then, L-lactide, glycolide, Sn(Oct) 2 , and additional toluene were added. The mixture was stirred for 24 hours at 120°C under nitrogen.…”