Polymeric drug delivery systems using micro and nanospheres containing violacein: characterization, biological activity, consenquences and perspectives

Author(s)

Marcelo Mantovani Martiniano Azevedo

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2005-06-29

Examining board members

Nelson Eduardo Duran Caballero; Miguel Jafelicci Junior; Emilia Celma de Oliveira Lima; Pedro Luiz Onófrio Volpe; Francisco Benedito Teixeira Pessine

• Advisor: Nelson Eduardo Duran Caballero

Abstract

In this work we investigate polymeric systems transporting violacein, substance of pharmacological interest, more specifically antitumoral, obtained from the biosynthesis of Chromobacterium violaceum. However, violacein is an insoluble compound in water and as a consequence introduces toxicity and low bioavailability, justifying the entrappment. Microspheres (PCL) were obtained according to well-known principles of obtainment and stabilization of colloidal systems, by the solvent evaporation method and nanospheres (PLGA) were obtained by "nanoprecipitation method" (phase separation). These systems were characterized regarding the physical-chemistry properties by optical, fluorescence and laser confocal microscopies, scanning electronic microscopy, transmission electronic microscopy, diameter distribution, zeta potencial and interfacial tension. Violacein entrapped in nanospheres promoted citotoxicity, cellular differentiation and apoptosis in leukaemia promyelocytic human HL60 cell line and fibroblasts V-79. Violacein in PCL microspheres is present in two forms: isolated and auto-associated, distributed along the particle and there is emission in diluted solution and when dispersed in the polymeric matrix The nanoparticulated system is cytotoxic for HL60, induces apoptosis (verified by transmembrane potential measures) and induces cellular differentiation. Inhibition of the mitochondrial swelling occurrence is caused by Pluronic membrane sealing capability to mitochondrial membrane, suggesting the direction to a specific target of the cell. (AU)