title: Controlled release and reversal of multidrug resistance by co-encapsulation of paclitaxel and verapamil in solid lipid nanoparticles.
abstract: Paclitaxel (PTX) has been used in the treatment of wide range of cancers but its entry into cancer cell is restricted by p-glycoprotein (p-gp). Also, it was reported that verapamil (VP) could inhibit p-gp efflux. Hence, three kinds of solid lipid nanoparticles (SLN) such as PVS (PTX and VP co-loaded SLN), PSV (PTX loaded SLN, later added VP) and PVSV (PTX and VP co-loaded SLN, later added VP) were prepared to overcome MDR by combination of PTX and VP. PVS was the SLN loaded with both PTX and VP at the same time. PSV was the SLN loaded with PTX and then modified with VP - complexed hydroxypropyl-β-cylcodextrin (HPCD). Finally, PVSV was the SLN loaded with PTX and half of VP at the same time subsequently, modified with half of VP - complexed HPCD. The physicochemical characterizations of PVS, PSV or PVSV such as particle size, zeta potential, encapsulation efficiency or in vitro PTX release were examined. PVSV showed that release of VP was higher than PTX solution in first 15h and sustained release of both VP and PTX. PVSV showed significantly higher cytotoxicity and cellular uptake than that of the PTX solution in MCF-7/ADR resistant cells. Furthermore, PVSV significantly down regulated the expression of p-gp than the PTX solution in MCF-7/ADR resistant cells. Based on these findings, this study indicated that the PVSV exhibited great potential for breast cancer therapy.
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea.
authors.forename: Jong-Suep
authors.initials: JS
authors.lastname: Baek
authors.affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon 305-764, South Korea. Electronic address: chocw@cnu.ac.kr.
authors.forename: Cheong-Weon
authors.initials: CW
authors.lastname: Cho
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D014700:Verapamil / Q000008:administration & dosage* / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D014700:Verapamil; D011065:Poly(ADP-ribose) Polymerases; D017239:Paclitaxel
keywords: Co-encapsulation; Multidrug resistance; Paclitaxel; Solid lipid nanoparticle; Verapamil