Temperature-responsive microcapsules prepared by nano-structured multilayers of chitosan and an elastin-like recombinamer for the controlled release of therapeutic molecules

Abstract

Objectives: Polyelectrolyte vesicles using layer-by-layer (LbL) were recently intro-duced for the encapsulation of therapeutic molecules. This work presents multilay-ered microcapsules of chitosan and a temperature-responsive elastin-like recom-binamer (ELR) as a novel drug delivery system. The release of a pre-loaded model protein was studied at distinct temperatures and number of layers to evaluate the permeability of these structures and their potential as tunable drug delivery devices. Methods: Sacrificial CaCO3 microparticles were prepared by co-precipitation of Na2CO3 and CaCl2 in a FITC-BSA solution under heavy stirring. LbL coating was performed by incubation with chitosan or ELR solutions, with a rinsing step in between. Capsules with 1, 3 and 5 bilayers were made. The CaCO3 cores were chelated using EDTA. The capsules were suspended in PBS at 25 and 37ºC and samples were taken every 24 hours for fluorescence measurements, during 14 days. Results: At both temperatures, cumulative release was higher for capsules with 1 bilayer, evidencing the role played by the capsules architecture in their perme-ability. The release kinetics among each temperature was also different: the BSA quantity released was higher at 25ºC than at 37ºC. Considering the case of a simple bilayer, in the former the cumulative release reaches 80%, while in the latter only 50% of the encapsulated protein is released. This result shows the effect of temperature in polyelectrolyte structures, namely when temperature-responsive materials like ELRs are used. Conclusions: Multilayered microcapsules based on chitosan and an ELR were studied as drug delivery vessels. Distinct release profiles of pre-loaded BSA at different temperatures and layer numbers demonstrated the influence of the capsules architecture and composition: more quantity of BSA is released for capsules with fewer layers and lower temperatures. These microcapsules have the potential for tunable drug release in tissue engineering applications by means of design changes.