pH-Triggered Sustained Drug Delivery from a Polymer Micelle having the [beta]-Thiopropionate Linkage

• Published in: Macromolecular rapid communications. 2016-09, Vol.37 (18), p.1499
• Main Authors: Pramanik, Prithankar, Halder, Debdatta, Jana, Siddhartha Sankar, Ghosh, Suhrit
• Format: Article
• Language: English
• ISSN: 1022-1336; 1521-3927
• DOI: 10.1002/marc.201600260

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 [beta]-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 [beta]-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.