Synthesis of poly(acrylic acid) (PAA) modified Pluronic P123 copolymers for pH-stimulated release of Doxorubicin

• Published in: Journal of colloid and interface science Vol. 358; no. 2; pp. 462 - 470
• Main Authors: Choo, Eugene Shi Guang, Yu, Bin, Xue, Junmin
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 15.06.2011; Elsevier
• Subjects: Acrylic Resins - chemical synthesis; Acrylic Resins - therapeutic use; Antineoplastic Agents - administration & dosage; Atom transfer radical polymerization (ATRP); Carriers; Cationic; Chemistry; composite polymers; Copolymers; Doxorubicin; Doxorubicin - administration & dosage; drug carriers; Drug Carriers - chemical synthesis; Drug Carriers - pharmacokinetics; Drug release; Drugs; Exact sciences and technology; General and physical chemistry; Hydrogen-Ion Concentration; pH-responsive; Poloxalene - chemical synthesis; Poloxalene - therapeutic use; polyacrylic acid; polymerization; Radicals; Self-assembly; Terminals; Drug release; Self-assembly; Doxorubicin; Atom transfer radical polymerization (ATRP); pH-responsive; Drug; Self assembly; Incorporation; Acrylic acid; Polymerization; Potential; Complexes; Assay; Synthesis; Poloxamer; pH; Environment; Copolymer; Release
• ISSN: 0021-9797; 1095-7103
• DOI: 10.1016/j.jcis.2011.03.047

The pH-induced release of Doxorubicin from poly(acrylic acid)-modified Pluronic P123 copolymer was verified through acidification of the drug release medium. [Display omitted] ► Pluronic P123 was chain-extended with PAA via ATRP followed by acidolysis. ► Aggregation behavior of the modified copolymers was investigated. ► pH-sensitivity incorporated to Pluronic P123 copolymer. ► Higher Doxorubicin loading capacity for PAA modified Pluronic P123. ► Accelerated release of Doxorubicin was achieved at pH 5. Pluronic P123 was chain-extended at their terminal groups using atom transfer radical polymerization to form poly(acrylic acid) (PAA) tails and obtain the PAA- b-P123- b-PAA (P123-PAA) copolymer. The incorporation of PAA had the effect of increasing the carrier’s drug loading capacity of an anti-cancer drug, Doxorubicin (DOX), and also allowed for pH-controlled release of the drug. Drug release assays showed that up to 60% of DOX cargo could be retained in the DOX/P123-PAA complex for 3 days at normal physiological pH (7.4). This was then followed by a secondary burst release of DOX when the environment became more acidic (pH 5). Therefore, it was possible that the more acidic physiological environment of tumor sites could be used to trigger an accelerated release of DOX from the drug carriers. The material was demonstrated for potential application in the delivery of cationic drugs for cancer treatment.