期刊
PHARMACEUTICAL RESEARCH
卷 25, 期 3, 页码 657-666出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-007-9480-4
关键词
degradable pH sensitive polymer; disulfide polymer; pH-sensitive polymer; tumor pH
资金
- NCI NIH HHS [CA122356] Funding Source: Medline
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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