title: Development of topotecan loaded lipid nanoparticles for chemical stabilization and prolonged release.
abstract: Topotecan is an important cytotoxic drug that has gained broad acceptance in clinical use for the treatment of refractory ovarian and small-cell lung cancer. The lactone active form of topotecan can be hydrolyzed in vivo, decreasing the drug's therapeutic efficacy. Lipid encapsulation may promote in vivo stabilization by removing topotecan from aqueous media. Earlier reports of topotecan lipid nanoencapsulation have focused on liposomal encapsulation; however, the higher stability and cost-effectiveness of solid lipid nanoparticles (SLN) highlight the potential of these nanoparticles as an advantageous carrier for topotecan. The initial motivation for this work was to develop, for the first time, solid lipid nanoparticles and nanostructured lipid carriers (NLC) with a high drug loading for topotecan. A microemulsion technique was employed to prepare SLNs and NLCs and produced homogeneous, small size, negatively charged lipid nanoparticles with high entrapment efficiency and satisfactory drug loading. However, low recovery of topotecan was observed when the microemulsion temperature was high and in order to obtain high quality nanoparticles, and precise control of the microemulsion temperature is critical. Nanoencapsulation sustained topotecan release and improved its chemical stability and cytotoxicity. Surprisingly, there were no significant differences between the NLCs and SLNs, and both are potential carriers for topotecan delivery.
authors.affiliation: Laboratory of Pharmaceutical Technology, Federal University of Goiás, Goiânia, Brazil.
authors.forename: L G
authors.initials: LG
authors.lastname: Souza
authors.forename: E J
authors.initials: EJ
authors.lastname: Silva
authors.forename: A L L
authors.initials: AL
authors.lastname: Martins
authors.forename: M F
authors.initials: MF
authors.lastname: Mota
authors.forename: R C
authors.initials: RC
authors.lastname: Braga
authors.forename: E M
authors.initials: EM
authors.lastname: Lima
authors.forename: M C
authors.initials: MC
authors.lastname: Valadares
authors.forename: S F
authors.initials: SF
authors.lastname: Taveira
authors.forename: R N
authors.initials: RN
authors.lastname: Marreto
mesh_terms: D002470:Cell Survival / Q000502:physiology; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding; D016503:Drug Delivery Systems; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D005612:Freeze Drying; D006801:Humans; D020014:K562 Cells; D008055:Lipids / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D049329:Nanostructures / Q000032:analysis / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D012995:Solubility; D013499:Surface Properties; D013696:Temperature; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D019772:Topotecan / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D014343:Trypan Blue
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D008055:Lipids; D059004:Topoisomerase I Inhibitors; D019772:Topotecan; D014343:Trypan Blue