title: pH-responsive copolymers based on pluronic P123-poly(β-amino ester): Synthesis, characterization and application of copolymer micelles.
abstract: A novel amphiphilic and pH-responsive copolymer, pluronie P123-poly(β-amino ester) (P123-PAE), was firstly designed and synthesized using a Michael-type step polymerization. Nano-sized polymeric micelles based on P123-PAE block copolymer were prepared by self-assembly. Curcumin (Cur), a potential cancer therapy drug, was efficiently encapsulated into the P123-PAE micelles to enhance anticancer efficacy. The obtained Cur loaded P123-PAE micelles (Cur-P123-PAE) presented a spherical shape and high drug loading (18.4%). Interestingly, when the media pH decreased from 7.4 to 5.5, the particle size of the micelles shrank from 152.5nm to 122.1nm due to the protonation of PAE blocks, and the zeta potential of the P123-PAE micelles changed from weakly positive (1.5mV) to highly positive (9.0mV) over a pH range from 7.4 to 5.5. In vitro drug release studies demonstrated that the release rate of Cur was markedly influenced by pH. In vitro cytotoxicity tests showed that all the blank micelles were non-toxic. Cur-P123-PAE exhibited similar antitumor effect against MCF-7 and HepG2 cells compared to solubilized Cur solution. Using Coumarin-6 as a fluorescence probe, it was observed that Cur-P123-PAE micelles experienced longer circulation followed by accumulation at tumor tissues with stronger fluorescence intensity. The results of pharmacokinetics studies showed that the P123-PAE micelles could significantly prolong the retention time of Cur in vivo.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China.
authors.forename: Mengrui
authors.initials: M
authors.lastname: Liu
authors.affiliation: School of Material Science and Engineering, Shandong University, Jinan 250061, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Second Hospital of Shandong University, Jinan 250033, China; School of Pharmaceutical Sciences, Shandong University, Jinan 250061, China. Electronic address: sundq0405@126.com.
authors.forename: Deqing
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000494:pharmacology*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry; D003474:Curcumin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers; D004339:Drug Compounding; D065546:Drug Liberation; D005456:Fluorescent Dyes / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008823:Micelles; D010316:Particle Size; D011060:Poloxalene / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D011108:Polymers / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008823:Micelles; D011108:Polymers; C507253:poly(beta-amino ester); C464484:pluronic block copolymer P123; D011060:Poloxalene; D003474:Curcumin
keywords: Cancer therapy; Curcumin; Poly(β-amino ester); Self-assembled micelles; pH-sensitive