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  • Title: Amorphous amphiphilic P(3HV-co-4HB)-b-mPEG block copolymer synthesized from bacterial copolyester via melt transesterification: nanoparticle preparation, cisplatin-loading for cancer therapy and in vitro evaluation.
    Author: Shah M, Ullah N, Choi MH, Kim MO, Yoon SC.
    Journal: Eur J Pharm Biopharm; 2012 Apr; 80(3):518-27. PubMed ID: 22178562.
    Abstract:
    Cisplatin is a chemotherapeutic agent used against a variety of tumors. We determined the efficacy and bioavailability of cisplatin in the form of cisplatin-loaded self-assembled amphiphilic copolymer nanoparticles (NPs). Non-crystallizing bacterial copolyester was employed as hydrophobic segment to increase drug loading efficiency. Novel amorphous amphiphilic block copolymer P(3HV-co-4HB)-b-mPEG was synthesized from bacterial copolyester poly(3-hydroxyvalerate-co-4-hydroxybutyrate) coupled via transesterification reaction using bis(2-ethylhexanoate) tin catalyst to monomethoxypoly(ethylene glycol). The product was characterized, and core-shell particles with nanometer size range were prepared by emulsification-solvent evaporation method. Transmission electron microscopy (TEM) examination revealed that the NPs took the shape of spheres with inner concealed core of hydrophobic P(3HV-co-4HB) polymer and the outer shell formed by hydrophilic mPEG segment. The in vitro release profile of cisplatin from the core hydrophobic domain showed a sustained release of the drug. TEM and confocal microscopy examination revealed clearly the internalization of cisplatin-loaded NPs into the tumor cells. MTT assay, flow cytometry, western blot and confocal microscopy revealed a suppression effect by the NPs on tumor cell growth, and enhancement of apoptotic process of the tumor cells compared to free drug treated cells. The amorphous polymeric NPs could be effective vehicles for the sustained delivery of toxic anticancer drugs.
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