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A Biodegradable pH-sensitive Micelle System for Targeting Acidic Solid Tumors

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Abstract

A new pH-sensitive micelle delivery system based on TAT cell penetrating peptide and biodegradable sulfonamide grafted disulfide polymer is presented. The system consists of two components: (1) A polymeric micelle made of Poly(l-lactic acid)-b-poly(ethylene glycol) (PLLA-b-PEG) conjugated to TAT (TAT-micelle), (2) A pH-sensitive diblock copolymer (poly(l-cystine bisamide-g-sulfadiazine))-b-PEG (PCBS-b-PEG). The anionic PCBS complexed with cationic TAT of TAT-micelles forms the final carrier. PCBS showed rapid degradation in the presence of cysteine. The TAT-micelles showed increase in particle size between pH 8.0 and 7.0 upon mixing with PCBS-b-PEG indicating complexation. As the pH was further decreased (pH 6.8 to 6.0) two populations were observed, one of normal TAT-micelles and the other of aggregated PCBS-b-PEG. Flow cytometry showed significantly higher uptake of TAT-micelles at pH 6.6 indicating deshielding compared to pH 7.4. The anticancer drug doxorubicin (DOX) was encapsulated into the TAT-micelles, and the in vitro cytotoxicity at different pHs was evaluated. The system was able to distinguish pHs 7.2 and 7.0 in terms of cytotoxicity.

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Acknowledgments

The authors wish to thank the Core Facilities at the University of Utah for use of the Mass and NMR spectroscopy and flow cytometer. This work was supported by NIH CA122356.

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Authors and Affiliations

  1. Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah, 84108, USA

    Vijay A. Sethuraman & You Han Bae

  2. Department of Chemical and Biochemical Engineering, Dongguk University, 3-26 Pil-dong, Choong gu, Seoul, 100-715, South Korea

    Myung Cheon Lee & You Han Bae

Authors
  1. Vijay A. Sethuraman
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  2. Myung Cheon Lee
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Correspondence to You Han Bae.

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Sethuraman, V.A., Lee, M.C. & Bae, Y.H. A Biodegradable pH-sensitive Micelle System for Targeting Acidic Solid Tumors. Pharm Res 25, 657–666 (2008). https://doi.org/10.1007/s11095-007-9480-4

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  • DOI: https://doi.org/10.1007/s11095-007-9480-4

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