title: Development of etoposide-loaded bovine serum albumin nanosuspensions for parenteral delivery.
abstract: Nanosuspensions emerge as a promising strategy for delivery of poorly water-soluble drugs. Albumin is a versatile protein carrier for drug delivery and targeting. The purpose of this study was to develop a formulation of etoposide-loaded bovine serum albumin (BSA) nanosuspensions, to study in vitro characterization, and to estimate the in vivo safety and tissue distribution of etoposide-loaded BSA nanosuspensions for parenteral delivery. Etoposide-loaded BSA nanosuspensions were prepared by high-pressure homogenization-solvent precipitation method. The particle size, zeta potential, drug entrapment efficiency, and drug loading of the lyophilized formulation were 182.3 nm, -22.18 mV, 86.44%, and 8.49% respectively. In vitro release files of the formulation presented sustained release properties. Preliminary safety study was conducted to evaluate the delivery system, and results indicated that myelosuppression effect of the etoposide-loaded BSA nanosuspensions group was significantly lower than the Injection® group. Furthermore, results of tissue distribution studies showed that the concentration and AUC of etoposide were increased significantly in lung, liver, spleen while reduced in heart, kidney compared with the etoposide injection® group after i.v. administration of etoposide-loaded BSA nanosuspensions. The formulation played a role in targeting delivery to lung, reduce toxicity, and side effects of etoposide. In conclusion, etoposide-loaded BSA nanosuspensions were promising for parenteral delivery of etoposide.
authors.affiliation: College of Pharmacy, Shandong University , Jinan , P.R. China .
authors.forename: Zhonglan
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhongwen
authors.initials: Z
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Miao
authors.forename: Guihua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005047:Etoposide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005612:Freeze Drying; D007275:Injections, Intravenous; D008168:Lung / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D012710:Serum Albumin, Bovine; D005047:Etoposide
keywords: Bovine serum albumin; etoposide; nanosuspensions; targeting delivery; tissue distribution