Poly ε-caprolactone nanoparticles loaded with Uncaria tomentosa extract: preparation, characterization, and optimization using the Box–Behnken design

Abstract

Ana Ferreira Ribeiro, Ricardo Leite de Oliveira Rezende, Lúcio Mendes Cabral, Valéria Pereira de SousaDepartment of Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilPurpose: The aim of this research was to develop and optimize a process for obtaining poly ε-caprolactone (PCL) nanoparticles loaded with Uncaria tomentosa (UT) extract.Methods: Nanoparticles were produced by the oil-in-water emulsion solvent evaporation method. Preliminary experiments determined the initial conditions of the organic phase (OP) and of the aqueous phase (AP) that would be utilized for this study. Ultimately, a three-factor three-level Box–Behnken design (BBD) was employed during the optimization process. PCL and polyvinyl alcohol (PVA) concentrations (X1 and X2, respectively) and the AP/OP volume ratio (X3) were the independent variables studied, while entrapment efficiency (Y1), particle mean diameter (Y2), polydispersity (Y3), and zeta potential (Y4) served as the evaluated responses.Results: Preliminary experiments revealed that the optimal initial conditions for the preparation of nanoparticles were as follows: OP composed of 5 mL ethyl acetate/acetone (3/2) mixture containing UT extract and PCL, and an AP of buffered PVA (pH 7.5) solution. Statistical analysis of the BBD results indicated that all of the studied factors had significant effects on the responses Y1, Y2, and Y4, and these effects are closely described or fitted by regression equations. Based on the obtained models and the selected desirability function, the nanoparticles were optimized to maximize Y1 and minimize Y2. These optimal conditions were achieved using 3% (w/v) PCL, 1% (w/v) PVA, and an AP/OP ratio of 1.7, with predicted values of 89.1% for Y1 and 280 nm for Y2. Another batch was produced under the same optimal conditions. The entrapment efficiency of this new batch was measured at 81.6% (Y1) and the particles had a mean size of 247 nm (Y2) and a polydispersity index of 0.062 (Y3).Conclusion: This investigation obtained UT-loaded nanoparticle formulations with desired characteristics. The BBD approach was a useful tool for nanoparticle development and optimization, and thus should be useful especially in the realm of phytotherapeutics, in which varied compositions may be assessed in quantitative and qualitative terms.Keywords: PCL, design of experiments, anti-tumorigenic, cat's claw, nanochemoprevention