title: Amino acid based amphiphilic copolymer micelles as carriers of non-steroidal anti-inflammatory drugs: solubilization, in vitro release and biological evaluation.
abstract: Three novel amino acid based anionic amphiphilic copolymers poly(sodium N-acryloyl-l-valinate-co-alkylacrylamide) (where, alkyl=octyl and dodecyl) with either 9 or 16 mol% hydrophobic substitution were synthesized. These hydrophobically modified polyelectrolytes (HMPs), above a critical concentration, self-assemble in aqueous solution through inter-chain hydrophobic aggregation, forming micelle-like aggregates having hydrodynamic diameter in the range of 50-200 nm. The HMPs were found to undergo conformational changes with the change in solution pH, electrolyte and additive concentration, and temperature. The polymeric micelles were observed to be stable under biological conditions (pH 7.4, [NaCl]=150 mM and temperature (37°C)). The solubilization capacity of the polymeric micelles for six important non-steroidal anti-inflammatory drugs of different hydrophobicity was evaluated. Depending upon the hydrophobicity the solubilities of the drugs were observed to increase ca. 2-10 times in the presence of 1.0 g/L copolymers. The in vitro release kinetics of the loaded drug was studied under physiological pH. To explore their potential application in pharmaceutical industries hemocompatibility and cytotoxicity studies were carried out using hemolytic and MTT assay, respectively. The anionic HMPs were found to be not directly toxic to mammalian cells.
authors.affiliation: Department of Chemistry, Indian Institute of Technology, Kharagpur, West Bengal 721302, India.
authors.forename: Pranabesh
authors.initials: P
authors.lastname: Dutta
authors.forename: Joykrishna
authors.initials: J
authors.lastname: Dey
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Perumal
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
mesh_terms: D016475:3T3 Cells; D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004573:Electrolytes / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013696:Temperature
chemical_list: D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D004573:Electrolytes; D008823:Micelles; D011108:Polymers; D013501:Surface-Active Agents