Folate-Conjugated Polymer Micelles with pH-Triggered Drug Release Properties
✍ Scribed by Haizheng Zhao; Hoang Hanh Phuoc Duong; Lin Yue Lanry Yung
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 561 KB
- Volume
- 31
- Category
- Article
- ISSN
- 1022-1336
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✦ Synopsis
Abstract
Folate has been applied as a targeting moiety for various anticancer drug‐delivery agents to avoid non‐specific attack of normal tissues as well as to increase cellular uptake at the target tumor cells. Polymer micelles made of poly[(D,L‐lactide)‐co‐glycolide)]‐poly(ethylene glycol)‐folate (PLGA‐PEG‐FOL) was fabricated as a tumor targeting carrier for encapsulating the anticancer drug doxorubicin. To accelerate the drug release in the endosome after folate‐mediated cellular uptake, pH‐sensitive poly(β‐amino ester)‐PEG‐FOL (PAE‐PEG‐FOL) was added together with PLGA‐PEG‐FOL to form mixed micelles. The results showed that the drug release can be triggered at different pH due to the ionization of PAE. The IC~50~ of PLGA‐PEG‐FOL micelles is 0.46 × 10^−6^ M. With 20% PAE in the mixed micelles (20:80 mixed micelles), the IC~50~ decreases to 0.34 × 10^−6^ M, which is comparable to that of pure PAE‐PEG‐FOL micelles at pH 7.4. As a result of the pH sensitivity, the PAE‐PEG‐FOL micelles are not stable at pH 6.5 or lower, and the drug may be released from the micelles into the extracellular environment before uptake by the cells. The 20:80 mixed micelles are relatively stable at this condition. As a result, the micelles retain more drug in the micelles for a higher degree of cellular uptake by folate receptor‐mediated endocytosis, and exhibit higher cytotoxicity.
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