Synthesis and evaluation of antitumor activity of plga microcapsules containing nor-beta-lapachone

• Autor(a) principal: Anderson Clayton SÃ Feitosa
• Data de Publicação: 2016
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
• Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=16547
• topic: CÃncer; MicrocÃpsulas; Nanotecnologia, nor-β; Lapachona; Cancer; Microcapsules; nanotechnology; Nor-β; Lapachone; FARMACOLOGIA GERAL

Nor-β-lapachone (NβL), a derivative compound obtained from nor-lapachol, is an important anti-cancer prototype. This semisynthetic naphthoquinone has been described as cytotoxic agent against several cancer cell lines. Regrettably, the use of this molecule has been limited due to the poor lipid solubility of compounds from the quinone class. In order to overcome this difficulty, we propose the synthesis of poly (lactide-co-glycolide) (PLGA) microparticles for NβL delivery. In this work, we characterize NβL-loaded microcapsules fabricated using the emulsification/solvent extraction technique. Features such as surface morphology, particle size distribution, zeta potential, optical absorption, Raman and Fourier transform infrared (FT-IR) spectroscopy, thermal analysis data, drug encapsulation efficiency, drug release kinetics and in vitro cytotoxicity were obtained. The microcapsules thus obtained showed appropriate morphological features (regular spherical shape, smooth surface and absence of pores). The presence of the compound inside the microcapsule was confirmed by Raman spectroscopy, and their release showed a biphasic profile. The first phase of the biphasic profile was due to dispersion of drug into the microcapsule surfaces. Quantum DFT calculations were also performed to estimate typical interaction energies between a single NβL molecule and the surface of the microparticles, with predicted binding energies varying from 6 kcal/mol to 52 kcal/mol. Spherical microcapsules with size of 1.03 Â 0.46 μm were produced with encapsulation efficiency of approximately 19%. The NβL-loaded PLGA microcapsules exhibited a pronounced initial burst release. After in vitro treatment with PLGA microcapsules loaded with NβL, it can be seen the incorporation of the microcapsules in the first hour. The cytotoxic activity of NβL against a set of cancer cell lines was investigated. In particular, the use of NβL against prostate PC3M cells was more effective when delivered in PLGA microcapsules compared to the free drug. In vivo assay, Sarcoma 180, reduces tumor weight approximately 37% in treated group with microcapsules loaded with NβL compared to negative control, without significant commitments in biochemical and hematological biomarkers. There was no free NβL absorption by the intraperitoneal route for the group treated with the free drug. These results suggest that PLGA microcapsules loaded with NβL can be used as an alternative delivery system to NβL administration at the prostate cancer therapy.