title: Preparation and characterization of the ion-fixed mixed micelles with superior stability.
abstract: The inherent instability of micelles remains a main challenge for antitumor drug delivery, the objective of this study is to prepare and characterize the ion-fixed mixed micelles with significantly improved stability. The mixed micelles and ion-fixed mixed micelles combining the carboxy-containing PLA (PLA-COO(-)) and mPEG-PLA were formed by inserting PLA-COO(-) into micellar core without and with metal ions, respectively. The critical micelle concentration (CMC) of mixed micelle depended on the origin PLA length in the mPEG-PLA, whereas kinetic stability of the mixed micelles was significantly improved, irrespective of the PLA length. However, curcumin (Cur)-loaded mixed micelles did not show higher physical stability upon dilution and Cur-micelle bonding constant due to the lower loading space. On the contrary, the ion-fixed mixed micelles formed in the presence of CaCl2 solution showed a high physical stability upon dilution due to the solidification of micellar core by forming the more hydrophobic (PLA-COO(-))2 Ca(2+) complex. The Cur-loaded ion-fixed mixed micelles showed the comparable cellular uptake of Cur and cytotoxicity in comparison with mPEG-PLA micelles. Our study highlights a universal combining strategy of ion-fixed mixed micelles with superior stability to individual micelles for antitumor drug delivery.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Lixue
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Huang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: pharm305@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology; D004339:Drug Compounding; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008823:Micelles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011721:Pyrenes / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011721:Pyrenes; C492425:methoxy poly(ethylene glycol)-poly(lactide); D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C030984:pyrene; D003474:Curcumin
keywords: Curcumin; Ion-fixed mixed micelle; Mixed micelle; PLA; Stability; mPEG-PLA