title: Preparation and characterization of poly lactide-co-glycolide nanoparticles of SN-38.
abstract: SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan (CPT-11), which is 100-1000-fold more cytotoxic than irinotecan. Nonetheless, the extreme hydrophobicity of SN-38 has prevented its clinical use. SN-38 is poorly soluble in aqueous solutions, and it is practically insoluble in most physiologically compatible and pharmaceutically acceptable solvents. One way of improving the solubility and stability of SN-38 is to formulate the drug into nanoparticles. Incorporation of cytotoxic agents into nanoparticles has also shown increased toxicity. In this study, poly lactide-co-glycolide was used for the preparation of nanoparticles of SN-38. The nanoparticles were fabricated by an emulsification/solvent evaporation method. The effect of several variables on nanoparticle characteristics was evaluated, including the ratio of drug-polymer, the amount of the poly vinyl alcohol as surfactant, and the internal phase volume/composition. The SN-38 encapsulation efficiency and the particle size distribution were optimized by varying these parameters. Nanoparticles were spherical with a relatively mono-dispersed size distribution. As the ratio of acetone to dichloromethane increased, a considerable decrease in the particle size of nanoparticles was achieved. The encapsulation efficiency of all samples was more than 80%. Changing the poly vinyl alcohol concentration in the external phase had some effects on size and morphology and encapsulation efficiency. It was shown that SN-38 nanoparticles are considerably stable in a long-term stability study.
authors.affiliation: Novel Drug Delivery Systems Lab, Faculty of Pharmacy, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: P
authors.initials: P
authors.lastname: Ebrahimnejad
authors.forename: R
authors.initials: R
authors.lastname: Dinarvand
authors.forename: S A
authors.initials: SA
authors.lastname: Sajadi
authors.forename: F
authors.initials: F
authors.lastname: Atyabi
authors.forename: F
authors.initials: F
authors.lastname: Ramezani
authors.forename: M R
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D057927:Hydrophobic and Hydrophilic Interactions; D000077146:Irinotecan; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles; D036103:Nanotechnology / Q000379:methods; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D012997:Solvents; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000077146:Irinotecan; D011142:Polyvinyl Alcohol; D002166:Camptothecin