Coencapsulation of trans-dehydrocrotonin and trans-dehydrocrotonin:hydroxypropyl-β-cyclodextrin into microparticles

Abstract

The aim of this study was to develop and characterize poly-ε-caprolactone (PCL) and poly(D,L-lactic-co-glycolic)-acid (PLGA) microparticles containing coencapsulated trans-dehydrocrotonin (t-DCTN) and t-DCTN:hydroxypropyl-β-cyclodextrin inclusion complex (t-DCTN:HP-β-CD), with t-DCTN loaded at concentrations ranging from 11.25 to 45.00 mg. A preformulation study was carried out using a 24-1 fractional factorial design. Microparticles were prepared using the double w/o/w emulsion-solvent evaporation method. The coencapsulated t-DCTN:HP-β-CD-loaded PLGA microparticles (t-DCTN/t-DCTN:HP-β-CD/PLGA-MPs) presented a smaller particle size (9.6 ± 0.1 µm) and higher drug loading (13.93 ± 0.05%, corresponding to 90.1 ± 0.3% of encapsulation efficiency, EE) and t-DCTN-loaded PLGA microparticles (t-DCTN/PLGA-MPs) presented particle size of 37.0 ± 0.2 µm and drug loading of 10.12 ± 0.01% (EE of 71.2 ± 0.1%). The coencapsulation of t-DCTN and t-DCTN:HP-β-CD into PLGA microparticles increased drug loading (50%) and improved the drug controlled release (k2 = 0.0475 and De = 0.0475 × 10-11 cm2 s-1). Taking into account these findings, new oral formulation of PLGA microparticles containing coencapsulated t-DCTN and t-DCTN:HP-β-CD are available as biocompatible drug delivery systems for further pharmacological purposes.