title: A highly stable norcantharidin loaded lipid microspheres: preparation, biodistribution and targeting evaluation.
abstract: The purpose of this study was to prepare norcantharidin (NCTD)-loaded lipid microspheres (LMs) with a high encapsulation efficiency (EE) and stability during sterilization. The NCTD-phospholipid complex (NPC) was produced and characterized to increase the lipophilic properties of NCTD and a novel concentrated homogenization method was applied for the preparation of LMs. The results of the UV, DSC and IR investigations confirmed the formation of NPC. The oil-water partition coefficient (log P) of NPC was significantly increased with a value of -1.34 ± 0.06 at pH 7.4, nearly 224 times higher than that of NCTD. A concentrated emulsion was prepared based on a homogenization method and then diluted with water. After optimization of the NPC formation and emulsion preparation process, the EE was dramatically increased from 21.6% to 84.6%, and a highly sterilization stability was achieved with only a minor change in particle size from 168.2 ± 39.4 nm to 173.4 ± 43.5 nm. The tissue distribution of NPCLM was measured after intravenous administration to rats of a dose of 3.9 mg/kg with NCTD injection (NI) as the reference. Considerably increased concentrations of NCTD in the liver, spleen and lung were detected with NPCLM and the values were 1.67, 1.49 and 1.06 times higher than in the NI group, respectively while, in the kidney, the concentration was slightly reduced 0.96-fold. Overall, based on these techniques, this NPCLM with an improved EE and stability offers great promise in clinical applications and industrial-scale production along with a potentially increased targeting effect on the liver and reduced toxicity in the kidney.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Ma
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Teng
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; Shenyang Jinchang Pharmaceutical Co., Ltd., China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China; Jiangsu Kanion Pharmaceutical Co., Ltd., China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Tianyang
authors.initials: T
authors.lastname: Ren
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: bbpharmcai@sina.com.
authors.forename: Cuifang
authors.initials: C
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D004339:Drug Compounding; D051379:Mice; D008863:Microspheres; D010743:Phospholipids / Q000737:chemistry; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010743:Phospholipids; C069741:norcantharidin
keywords: Concentrated homogenization; Encapsulation efficiency; Norcantharidin; Phospholipid complex; Targeting efficiency; Tissue distribution