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  • Title: CPT loaded nanoparticles based on beta-cyclodextrin-grafted poly(ethylene glycol)/poly (L-glutamic acid) diblock copolymer and their inclusion complexes with CPT.
    Author: Du F, Meng H, Xu K, Xu Y, Luo P, Luo Y, Lu W, Huang J, Liu S, Yu J.
    Journal: Colloids Surf B Biointerfaces; 2014 Jan 01; 113():230-6. PubMed ID: 24096159.
    Abstract:
    This research is aimed to develop a nanoparticle delivery system based on β-cyclodextrin-grafted diblock copolymer and camptothecin (CPT) inclusion complexes with the purpose of enhancing the stability of CPT in aqueous media. Firstly, mPEG-PBLG diblock copolymer was synthesized by the ring-opening polymerization of γ-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) initiated with amine terminated poly (ethylene glycol) monomethyl ether (mPEG-NH2). After removal of benzyl groups, mono-6-amine-β-cyclodextrin (EDA-β-CD) units were coupled to the carboxyl groups of the copolymer as side groups to produce the host macromolecule mPEG-PLG(CD). The highly hydrophobic anticancer drug CPT was employed as the guest component which could be included into the host macromolecule to form supramolecular inclusion-complex mPEG-PLG(CPT@CD). Interestingly, the supramolecular complexes were able to form spherical nanoparticles with an average size of 98 nm in aqueous media confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM), suggesting their passive targeting potential to tumor tissue. Due to the protection effect from a dual lock system (the environment of nanoparticles and the exterior surface of β-CD), the active lactone ring of CPT showed remarkably enhanced stability against hydrolysis under physiological condition. The release profile of the mPEG-PLG(CPT@CD) nanoparticles in PBS buffer was found to be gradual and sustaining. It was worthy to note that the release could be accelerated by addition of adamantane carboxylate (ADC) as competitive guest compound, demonstrating the chemically stimulated release behavior of the nanoparticles. Compared with free CPT, the mPEG-PLG(CPT@CD) nanoparticles displayed essentially decreased cytotoxicity against MCF-7 cell line in 24 h because of a sustained release profile of CPT from the nanoparticles, moreover, the carrier mPEG-PLG(CD) itself showed almost no cytotoxicity, indicating its great potential as tumor tissue targeted drug delivery system.
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