RESUMEN
Objective: To prepare killer peptide-loaded PLGA nanoparticles which have better effect in treating systemic crypotococcosis. Methods: We adopted a modified double-emulsion method to prepare the killer peptide-loaded PLGA noparticles, and the nanoparticles were characterized by using TEM, SEM, Dynamic Laser Scattering, drug loading analysis, ecapsulation efficacy assessment and in vitro release test. We also evaluated the antifungal activities of killer peptide and killer peptide-loaded PLGA nanoparticles against Cry ptOcoccus neoformans ATCC32609 by plate count method. In the in vivo study, the anticryptococcal efficacies of killer peptide and killer peptide-loaded PLGA nanoparticles were compared by observing the survival and colony-forming in vital organs in a systemic murine cryptococcosis model. Results1 We successfully synthesized killer peptide-loaded PLGA nanoparticles. In vitro anticryptococcal test showed that the killer peptide and killer peptide-loaded PLGA nanoparticles had significantly stronger anticryptococcal effect compared with the normal saline group (P0.05). In vits test demonstrated that mice treated with killer peptide-loaded PLGA nanoparticles (3 mg/kg or 5 mg/kg) had longer survival period and less fungal burden in vital organs than mice treated with free killer peptide (P0.05). Conclusion: The killer peptide-loaded PLGA nanoparticles are more effective in treating systemic murine cryptococcosis.
RESUMEN
Peptides are remarkably reactive molecules produced by a great variety of species and able to display a number of functions in uni-and multicellular organisms as mediators, agonists and regulating substances. Some of them exert cytotoxic effects on cells other than those that produced them, and may have a role in controlling subpopulations and protecting certain species or cell types. Presently, we focus on antifungal and antitumor peptides and discuss a few models in which specific sequences and structures exerted direct inhibitory effects or stimulated a protective immune response. The killer peptide, deduced from an antiidiotypic antibody, with several antimicrobial activities and other Ig-derived peptides with cytotoxic activities including antitumor effects, are models studied in vitro and in vivo. Peptide 10 from gp43 of P. brasiliensis (P10) and the vaccine perspective against paracoccidioidomycosis is another topic illustrating the protective effect in vivo against a pathogenic fungus. The cationic antimicrobial peptides with antitumor activities are mostly reviewed here. Local treatment of murine melanoma by the peptide gomesin is another model studied at the Experimental Oncology Unit of UNIFESP.
Peptídeos são moléculas particularmente reativas produzidas por uma grande variedade de espécies, aptos a exercer um número de funções em organismos uni-e multicelulares como mediadores, agonistas e substâncias regulatórias. Alguns deles exercem efeitos citotóxicos em células outras das que os produzem, e podem ter um papel controlando subpopulações e protegendo certas espécies ou tipos celulares. No presente, focalizamos peptídeos antifúngicos e antitumorais e discutimos alguns modelos nos quais seqüências específicas e estruturas exercem efeitos inibitórios diretos ou estimulam uma resposta imune protetora. O peptídeo letal ("killer"), deduzido de um anticorpo anti-idiotípico, com várias atividades antimicrobianas bem como outros peptídeos derivados de imunoglobulinas com atividades citotóxicas incluindo efeitos antitumorais são modelos estudados in vitro e in vivo. O peptídeo P10 da gp43 de P. brasiliensis e a perspectiva de vacina contra a paracoccidioidomicose é outro tópico ilustrando o efeito protetor in vivo contra um fungo patogênico. Peptídeos antimicrobianos catiônicos com atividades antitumorais são os principais revistos aqui. O tratamento local do melanoma murino com o peptídeo gomesina é outro modelo estudado na Unidade de Oncologia Experimental (UNONEX) da UNIFESP.