Chirality plays critical roles in enhancing the aqueous solubility of nocathiacin I by block copolymer micelles

Authors

  • Kun Feng,

    1. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China
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  • Shuzhen Wang,

    1. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China
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  • Hairong Ma,

    1. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China
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  • Yijun Chen

    Corresponding author
    1. State Key Laboratory of Natural Medicines and Laboratory of Chemical Biology, China Pharmaceutical University, Nanjing, China
    2. Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, USA
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  • Kun Feng and Shuzhen Wang contributed equally to this work.

Yijun Chen, Laboratory of Chemical Biology, China Pharmaceutical University, 24 Tongjia Street, Nanjing 210009, People's Republic of China. E-mail: yjchen@cpu.edu.cn, yjchen_cpu@yahoo.com.cn

Abstract

Objectives  Although drug solubilization by block copolymer micelles has been extensively studied, the rationale behind the choice of appropriate block copolymer micelles for various poorly water-soluble drugs has been of relatively less concern. The objective of this study was to use methoxy-poly(ethylene glycol)-polylactate micelles (MPEG-PLA) to solubilize glycosylated antibiotic nocathiacin I and to compare the effects of chirality on the enhancement of aqueous solubility.

Methods  Nocathiacin I-loaded MPEG-PLA micelles with opposite optical property in PLA were synthesized and characterized. The drug release profile, micelle stability and preliminary safety properties of MPEG-PLA micelles were evaluated. Meanwhile, three other poorly water-soluble chiral compound-loaded micelles were also prepared and compared.

Key findings  The aqueous solubility of nocathiacin I was greatly enhanced by both l- and d-copolymers, with the degree of enhancement appearing to depend on the chirality of the copolymers. Comparison of different chiral compounds confirmed the trend that aqueous solubility of chiral compounds can be more effectively enhanced by block copolymer micelles with specific stereochemical configuration.

Conclusions  The present study introduced chiral concept on the selection and preparation of block copolymer micelles for the enhancement of aqueous solubility of poorly water-soluble drugs.

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