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pH‐Triggered Sustained Drug Delivery from a Polymer Micelle having the β‐Thiopropionate Linkage
Author(s) -
Pramanik Prithankar,
Halder Debdatta,
Jana Siddhartha Sankar,
Ghosh Suhrit
Publication year - 2016
Publication title -
macromolecular rapid communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.348
H-Index - 154
eISSN - 1521-3927
pISSN - 1022-1336
DOI - 10.1002/marc.201600260
Subject(s) - chemistry , micelle , biocompatibility , amphiphile , methacrylate , nile red , copolymer , drug delivery , pyrene , hydrolysis , drug carrier , polymer chemistry , polymer , hydrophobic effect , side chain , biophysics , combinatorial chemistry , organic chemistry , aqueous solution , fluorescence , physics , quantum mechanics , biology
The synthesis, micellar aggregation, and pH‐triggered intracellular drug delivery ability of an amphiphilic statistical copolymer (P2) are studied. Two methacrylate derivatives, one containing a hydrophilic pendant and the other containing a hydrophobic pendant chain, are copolymerized to produce P2. The hydrophobic pendant chain is linked to the polymer backbone by a β‐thiopropionate linkage, known to undergo slow hydrolysis at mild acidic pH. P2 forms a multimicellar cluster in water with a critical aggregation concentration of 0.02 mg mL −1 and encapsulates a hydrophobic guest such as pyrene, Nile red, or the anti‐cancer drug doxorubicin (Dox). Sustained release of the entrapped Dox (80% after 100 h) is noticed at pH 5.2, while release is significantly slower (35% after 100 h) at pH 7.4. Acidic hydrolysis of the β‐thiopropionate linkage leading to the reduction of the hydrophobicity is established as the cause for micellar disassembly and triggered drug release. Cell‐culture studies with the human breast cancer cell line, MCF‐7, reveal biocompatibility of P2 (below 150 μg mL −1 ). It is further tested for intracellular delivery of Dox. MCF‐7 cells remain healthy at pH 7.4 but become unhealthy at pH 5.2 when treated with a Dox‐loaded P2 micelles.