title: pH-Triggered Sustained Drug Delivery from a Polymer Micelle having the β-Thiopropionate Linkage.
abstract: 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.
authors.affiliation: Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
authors.forename: Prithankar
authors.initials: P
authors.lastname: Pramanik
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
authors.forename: Debdatta
authors.initials: D
authors.lastname: Halder
authors.affiliation: Department of Biological Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India. bcssj@iacs.res.in.
authors.forename: Siddhartha Sankar
authors.initials: SS
authors.lastname: Jana
authors.affiliation: Polymer Science Unit, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India. psusg2@iacs.res.in.
authors.forename: Suhrit
authors.initials: S
authors.lastname: Ghosh
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008823:Micelles; D015394:Molecular Structure; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D011422:Propionates / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013499:Surface Properties; D014407:Tumor Cells, Cultured
chemical_list: D008823:Micelles; D011108:Polymers; D011422:Propionates; D013438:Sulfhydryl Compounds; D004317:Doxorubicin
keywords: amphiphilic polymers; doxorubicin; drug delivery; pH-responsive micelles; β-thiopropionate linkages