Journal
JOURNAL OF CONTROLLED RELEASE
Volume 126, Issue 2, Pages 130-138Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2007.11.014
Keywords
polymeric mixed micelles; pH sensitive; drug delivery; poly(L-Histidine); tumor pH
Funding
- NCI NIH HHS [R01 CA101850-01A1, CA101850, R01 CA101850] Funding Source: Medline
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A novel pH-sensitive polymeric micellar system composed of poly(L-Histidine)-b-poly(ethylene glycol) and poly(L-Lactide)-b-poly(ethylene glycol) block copolymers was studied by dynamic/static light scattering, spectrofluorimetry and differential scanning calorimetry. The mixed micelles displayed ultra pH sensitivity which could be tuned by varying the mixing ratio of the two polymers. In particular, mixed micelles composed of 25 wt.% poly(L-Lactide)-b-poly(ethylene glycol) exhibited desirable pH dependency which could be used as a drug delivery system that selectively targeted the extracellular pH of acidic solid tumors. Micelles were quite stable from pH 7.4 to 7.0 but underwent a two-stage destabilization as pH decreased further. A significant increase in size and aggregation number was observed when pH dropped to 6.8. Further disruption of the micelle core eventually caused phase separation in the micelle core and dissociation of ionized poly(L-Histidine)-b-poly(ethylene glycol) molecules from the micelles as pH decreased to 6.0. Increased electrostatic repulsions which arise from the progressive protonation of imidazole rings overwhelming the hydrophobic interactions among uncharged neutral blocks is considered to be the mechanism for destabilization of the micelle core. (c) 2007 Elsevier B.V. All rights reserved.
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