title: Nanostructured lipid-carrageenan hybrid carriers (NLCCs) for controlled delivery of mitoxantrone hydrochloride to enhance anticancer activity bypassing the BCRP-mediated efflux.
abstract: Novel nanostructured lipid-carrageenan hybrid carriers (NLCCs) were exploited for controlled delivery of water soluble chemotherapeutic agent mitoxantrone hydrochloride (MTO) with high loading capacity, sustained release property, and potential for improving oral bioavailability and antitumor efficacy. By introducing the negative polymer of carrageenan, MTO was highly incorporated into NLCCs with encapsulation efficiency of 95.8% by electrostatic interaction. In vivo pharmacokinetics of MTO solution (MTO-Sol) and MTO-NLCCs in rats demonstrated that the apparent bioavailability of MTO-NLCCs was increased to approximate 3.5-fold compared to that of MTO-Sol. The cytotoxicity investigations by MTT method indicated that NLCCs could significantly enhanced the antitumor efficacy against resistant MCF-7/MX cells. The relative cellular association of MTO-NLCCs was 9.2-fold higher than that of MTO-Sol in breast cancer resistance protein (BCRP) over-expressing MCF-7/MX cells, implying that BCRP-mediated drug efflux was diminished by the introduction of NLCCs. The endocytosis inhibition study implied that the NLCCs entered the MCF-7/MX cells by clathrin-mediated endocytosis process, which can bypass the efflux of MTO mediated by BCRP. The new developed NLCCs provide an effective strategy for oral delivery of water-soluble MTO with improved encapsulation efficiency, oral bioavailability, and cytotoxicity against resistant breast cancer cells.
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China ;
authors.forename: Guixia
authors.initials: G
authors.lastname: Ling
authors.affiliation: b Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
authors.affiliation: b Department of Pharmaceutical Analysis, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China ;
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: a Department of Pharmaceutics, School of Pharmacy , Shenyang Pharmaceutical University , Shenyang , China ;
authors.forename: Zhonggui
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy; D002351:Carrageenan / Q000737:chemistry*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D008297:Male; D008942:Mitoxantrone / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D049329:Nanostructures / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008055:Lipids; D002351:Carrageenan; D008942:Mitoxantrone
keywords: Breast cancer resistance protein (BCRP); carrageenan; cellular association; mitoxantrone hydrochloride; nanostructured lipid–carrageenan hybrid carriers (NLCCs); oral bioavailability