title: Stealth and non-stealth nanocapsules containing camptothecin: in-vitro and in-vivo activity on B16-F10 melanoma.
abstract: Camptothecin (CPT) is an alkaloid that displays considerable antitumour activity, but clinical use has been limited by its poor water solubility and the instability of the lactone moiety (active form) in physiological media. We have therefore formulated the drug into nanocarrier systems in an attempt to improve its therapeutic properties. This study evaluates the effect of intraperitoneally administered stealth and non-stealth nanocapsules containing CPT on lung metastatic spread in mice inoculated with B16-F10 melanoma cells, and on the cytotoxic activity against B16-F10 melanoma cells in-vitro. Poly (D,L-lactide) PLA (non-stealth) and methoxy polyethylene glycol-(D,L-lactide) (PLA-PEG) (stealth) nanocapsules (49 and 66.6 kDa) were prepared by interfacial deposition of preformed polymer. CPT, as free drug or as drug-loaded nanocapsules, was administrated at a dose of 0.5 mg kg(-1) at 3-day intervals for 17 days. Free drug and CPT-loaded nanocapsules reduced the number of metastatic nodules by 45.09-91.76% (P < 0.05 vs positive control). However, only CPT-loaded PLA-PEG 49 kD nanocapsules significantly decreased the number of lung metastases when compared with free drug (P < 0.05). The administration of CPT-loaded nanocapsules and free drug did not result in neutropenia at the administered dose. The improved effectiveness of pegylated nanocapsules was attributed to protection of the drug by nanoencapsulation and to reduced uptake of particles by macrophages located in the lymph nodes. This assumption was supported by the in-vitro study, in which both PLA and 49 kDa PLA-PEG nanocapsules containing CPT were more cytotoxic than the free drug against B16-F10 melanoma cells.
authors.affiliation: Laboratório de Farmacotécnica, Departamento de Ciências Farmacêuticas, Universidade Federal de Santa Catarina, Brazil.
authors.forename: Gecioni
authors.initials: G
authors.lastname: Loch-Neckel
authors.forename: Daiane
authors.initials: D
authors.lastname: Nemen
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Puhl
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernandes
authors.forename: Marco Augusto
authors.initials: MA
authors.lastname: Stimamiglio
authors.forename: Márcio
authors.initials: M
authors.lastname: Alvarez Silva
authors.forename: Mirela
authors.initials: M
authors.lastname: Hangai
authors.forename: Maria Claúdia
authors.initials: MC
authors.lastname: Santos Silva
authors.forename: Elenara
authors.initials: E
authors.lastname: Lemos-Senna
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007274:Injections, Intraperitoneal; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053769:Nanocapsules; D009503:Neutropenia / Q000139:chemically induced; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D053769:Nanocapsules; D011091:Polyesters; C492425:methoxy poly(ethylene glycol)-poly(lactide); D011092:Polyethylene Glycols; C033616:poly(lactide); D002166:Camptothecin