title: The effective encapsulation of a hydrophobic lipid-insoluble drug in solid lipid nanoparticles using a modified double emulsion solvent evaporation method.
abstract: Raloxifene HCl (RH), a selective estrogen receptor modulator (SERM), is indicated for the prophylaxis or treatment of postmenopausal osteoporosis. RH shows extremely poor bioavailability due to limited solubility and an extensive intestinal/hepatic first-pass metabolism. Solid lipid nanoparticles (SLNs) are valuable carriers that can enhance drug bioavailability. However, in the case of RH, the encapsulation of the drug in SLNs remains a challenge because of its poor solubility in both water and lipids. In this study, a series of RH-containing SLNs (RH-SLNs) were generated using a modified double emulsion solvent evaporation (DESE) method. Briefly, RH with various drug/lipid ratios was solubilized in the inner core of a double emulsion using different water/organic solvent mixtures. Our best formulation was achieved with the formation of negatively charged nanoparticles, 180nm in diameter, with an encapsulation and loading efficiency of 85% and 4.5%, respectively. It also showed a Fickian mechanism of the drug release in the basic dissolution media. Thermal analysis revealed a distinct decrease in the crystallinity of lipids and RH in comparison with the unprocessed materials. The results of a cell viability assay also showed a better antiproliferative effect of the drug-loaded SLNs versus the free drug solution. Thus, these results indicated that the modified DESE method could be proposed for the effective encapsulation of RH in SLNs with appropriate physicochemical and biological properties.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran; Faculty of Pharmacy, Shahid Sadoughi University of Medical Science, Yazd, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Nabi-Meibodi
authors.forename: Alireza
authors.initials: A
authors.lastname: Vatanara
authors.forename: Abdolhossein Rouholamini
authors.initials: AR
authors.lastname: Najafabadi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Rouini
authors.forename: Vahid
authors.initials: V
authors.lastname: Ramezani
authors.forename: Kambiz
authors.initials: K
authors.lastname: Gilani
authors.forename: Seyed Mohammad Hossein
authors.initials: SM
authors.lastname: Etemadzadeh
authors.forename: Kayhan
authors.initials: K
authors.lastname: Azadmanesh
mesh_terms: D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004655:Emulsions; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000493:pharmacokinetics; D012995:Solubility
chemical_list: D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D020849:Raloxifene Hydrochloride
keywords: Double emulsion solvent evaporation; Entrapment efficiency; Loading efficiency; Raloxifene HCl; Solid lipid nanoparticles