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  • Title: Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin.
    Author: Guo Q, Luo P, Luo Y, Du F, Lu W, Liu S, Huang J, Yu J.
    Journal: Colloids Surf B Biointerfaces; 2012 Dec 01; 100():138-45. PubMed ID: 22766290.
    Abstract:
    Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.
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