title: Covalent and non-covalent curcumin loading in acid-responsive polymeric micellar nanocarriers.
abstract: Poor aqueous solubility, potential degradation, rapid metabolism and elimination lead to low bioavailability of pleiotropic impotent curcumin. Herein, we report two types of acid-responsive polymeric micelles where curcumin was encapsulated via both covalent and non-covalent modes for enhanced loading capacity and on-demand release. Biodegradable methoxy poly(ethylene glycol)-poly(lactic acid) copolymer (mPEG-PLA) was conjugated with curcumin via a hydrazone linker, generating two conjugates differing in architecture (single-tail versus double-tail) and free curcumin was encapsulated therein. The two micelles exhibited similar hydrodynamic size at 95 ± 3 nm (single-tail) and 96 ± 3 nm (double-tail), but their loading capacities differed significantly at 15.0 ± 0.5% (w/w) (single-tail) and 4.8 ± 0.5% (w/w) (double-tail). Under acidic sink conditions (pH 5.0 and 6.0), curcumin displayed a faster release from the single-tail nanocarrier, which was correlated to a low IC50 of 14.7 ± 1.6 (μg mL(-1)) compared to the value of double-tail micelle (24.9 ± 1.3 μg mL(-1)) in HeLa cells. The confocal imaging and flow cytometry analysis demonstrated a superior capability of single-tail micelle for intracellular curcumin delivery, which was a consequence of the higher loading capacity and lower degree of mPEG surface coverage. In conclusion, the dual loading mode is an effective means to increase the drug content in the micellar nanocarriers whose delivery efficiency is highly dependent on its polymer-drug conjugate architecture. This strategy offers an alternative nanoplatform for intracellularly delivering impotent hydrophobic agents (i.e. curcumin) in an efficient stimuli-triggered way, which is valuable for the enhancement of curcumin's efficacy in managing a diverse range of disorders.
authors.affiliation: School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Aiping
authors.initials: A
authors.lastname: Fan
authors.forename: Ju
authors.initials: J
authors.lastname: Zhang
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D002470:Cell Survival / Q000187:drug effects*; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D007773:Lactates / Q000737:chemistry*; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; C088513:poly(lactic acid-ethylene glycol); D011092:Polyethylene Glycols; D003474:Curcumin