Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells.

Marcilia Costa,Eufrânio Da Silva,Bruno Sousa,Ewerton Caetano,Valder Freire,Cláudia Pessoa,Bruno Cavalcanti,Gleiston Dias,Francisco Sales,Ito Barroso-Neto,Rainer Fischer,Luiz Ladeira,Fátima Oliveira,Stefano Di Fiore,Anderson Feitosa

doi:10.3390/molecules21070873

Abstract

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(d,l-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03 ± 0.46 μm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Highlights

IntroductionCancer is a progressive disease characterized by abnormal cell growth in which cells lose control over proliferation, overcome senescence, and become immortal and eventually malignant [1,2,3]
Cancer is a progressive disease characterized by abnormal cell growth in which cells lose control over proliferation, overcome senescence, and become immortal and eventually malignant [1,2,3].Molecules 2016, 21, 873; doi:10.3390/molecules21070873 www.mdpi.com/journal/moleculesThe molecular basis of cancer involves a combination of gain-of-function mutations in oncogenes and loss-of-function mutations in tumor-suppressor genes, often combined with epigenetic effects on gene expression [3]
PLGA microcapsule formulations were prepared by the emulsion solvent evaporation method, and the simple emulsion method was the most satisfactory for the preparation of NβL-loaded microcapsules

Summary

Introduction

Cancer is a progressive disease characterized by abnormal cell growth in which cells lose control over proliferation, overcome senescence, and become immortal and eventually malignant [1,2,3]. Lapachol is a naturally occurring naphthoquinone isolated from the heartwood of species belonging to the Bignoniaceae family (Tapebuia sp.) (Figure 1), which along with its derivatives have been extensively investigated for the treatment of cancer [20] Within this group, β-lapachone, one of the most widely-studied naphthoquinones, has presented a potent cytotoxic activity against several human cancer cell lines [21,22], requiring for its bioactivation the enzyme NAD(P)H:quinone oxidoreductase 1. Structural modifications modifications of Currently, strategies for cancer treatment based on controlled delivery systems are able to optimize the therapeutic effect of drugs and reduce toxic side effects [37,38,39,40,41,42,43,44] In this sense, nanoparticles and microcapsules are important vehicles for drug delivery [45]. To the best of our knowledge, this is the first study involving controlled release of nor-β-lapachone microparticles and it represents a new strategy to improve the antitumor activity of this important naphthoquinone

Results and Discussion

Characterization

Materials and Methods

Conclusions