title: Preparation, characterization and in vitro cytotoxicity of paclitaxel-loaded sterically stabilized solid lipid nanoparticles.
abstract: In an effort to develop an alternative formulation of paclitaxel suitable for parenteral administration, paclitaxel-loaded sterically stabilized solid lipid nanoparticles (SLNs) were prepared, characterized and examined for in vitro cytotoxicity. The SLNs, comprising trimyristin (TM) as a solid lipid core and egg phosphatidylcholine and pegylated phospholipid as stabilizers, were prepared using a hot homogenization method. Regardless of paclitaxel loading, the particle sizes and zeta potentials of the prepared SLNs were around 200nm and -38mV, respectively, suggesting that they would be suitable as a parenteral formulation. Cryo-scanning electron microscopy showed that the SLNs were homogeneous and spherical in shape, while differential scanning calorimetry measurement of the melting peak revealed that the TM exists as a solid in our formulation. Paclitaxel was loaded to the solid cores at a w/w ratio of 6%. Gel column chromatography showed that paclitaxel co-eluted with the phospholipids, indicating that paclitaxel was incorporated in the SLNs. An in vitro drug release study showed that paclitaxel was released from the SLNs in a slow but time-dependent manner. Furthermore, treatment of the OVCAR-3 human ovarian cancer cell line and the MCF-7 breast cancer cell line with paclitaxel-loaded SLNs yielded cytotoxicities comparable to those of a commercially available Cremophor EL-based paclitaxel formulation. These results collectively suggest that our optimized SLN formulation may have a potential as alternative delivery system for parenteral administration of paclitaxel.
authors.affiliation: Laboratory of Excellency for Drug and Gene Delivery, College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Soo-Jeong
authors.initials: SJ
authors.lastname: Lim
authors.forename: Chong-Kook
authors.initials: CK
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010051:Ovarian Neoplasms / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010316:Particle Size
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008055:Lipids; D017239:Paclitaxel