title: Ascorbyl palmitate/d-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo.
abstract: The roles of ginsenoside compound K (CK) in inhibiting tumor have been widely recognized in recent years. However, low water solubility and significant P-gp efflux have restricted its application. In this study, CK ascorbyl palmitate (AP)/d-α-tocopheryl polyethylene glycol 1000 succinate monoester (TPGS) mixed micelles were prepared as a delivery system to increase the absorption and targeted antitumor effect of CK. Consequently, the solubility of CK increased from 35.2±4.3 to 1,463.2±153.3 μg/mL. Furthermore, in an in vitro A549 cell model, CK AP/TPGS mixed micelles significantly inhibited cell growth, induced G0/G1 phase cell cycle arrest, induced cell apoptosis, and inhibited cell migration compared to free CK, all indicating that the developed micellar delivery system could increase the antitumor effect of CK in vitro. Both in vitro cellular fluorescence uptake and in vivo near-infrared imaging studies indicated that AP/TPGS mixed micelles can promote cellular uptake and enhance tumor targeting. Moreover, studies in the A549 lung cancer xenograft mouse model showed that CK AP/TPGS mixed micelles are an efficient tumor-targeted drug delivery system with an effective antitumor effect. Western blot analysis further confirmed that the marked antitumor effect in vivo could likely be due to apoptosis promotion and P-gp efflux inhibition. Therefore, these findings suggest that the AP/TPGS mixed micellar delivery system could be an efficient delivery strategy for enhanced tumor targeting and antitumor effects.
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Youwen
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Deyin
authors.initials: D
authors.lastname: Tong
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Daobiao
authors.initials: D
authors.lastname: Che
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Pei
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xia
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Hospital Pharmacy, The First Hospital of Suqian, Suqian, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
mesh_terms: D000072283:A549 Cells; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008819:Mice, Nude; D008823:Micelles; D013386:Succinates / Q000737:chemistry*; D047368:Tumor Burden / Q000187:drug effects; D014810:Vitamin E / Q000737:chemistry*
chemical_list: D001205:Ascorbic Acid; D036145:Ginsenosides; D008823:Micelles; D013386:Succinates; D014810:Vitamin E; C112772:ginsenoside compound K; C014225:tocophersolan; C031226:6-O-palmitoylascorbic acid
keywords: TPGS; anti-tumor therapy; ascorbyl palmitate; ginsenoside CK; mixed micelles