title: Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study.
abstract: Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic(®) P123, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60 ± 5.02 nm, 0.589 ± 0.198, 96.87% ± 9.04%, and 12.18% ± 1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17-7.7 μg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were >200, >200, and 110 μM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration-time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core-shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ling-Chun
authors.initials: LC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ying-Chen
authors.initials: YC
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Yu
authors.initials: CY
authors.lastname: Su
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chung-Shu
authors.initials: CS
authors.lastname: Hong
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsiu-O
authors.initials: HO
authors.lastname: Ho
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan; Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ming-Thau
authors.initials: MT
authors.lastname: Sheu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006801:Humans; D054709:Lecithins / Q000737:chemistry*; D008297:Male; D008823:Micelles; D011108:Polymers / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D054709:Lecithins; D008823:Micelles; D011108:Polymers; D011794:Quercetin
keywords: DSPE-PEG; Pluronic®; bioavailability; lecithin; micelle; mixed micelles; quercetin