Biodegradable porous micro/nanoparticles with thermoresponsive gatekeepers for effective loading and precise delivery of active compounds at the body temperature

Abstract

Abstract Stimuli-responsive controlled delivery systems are of interest for preventing premature leakages and ensuring precise releases of active compounds at target sites. In this study, porous biodegradable micro/nanoparticles embedded with thermoresponsive gatekeepers are designed and developed based on Eudragit RS100 (PNIPAM@RS100) and poly(N-isopropylacrylamide) via a double emulsion solvent evaporation technique. The effect of initiator types on the polymerization of NIPAM monomer/methylene-bis-acrylamide (MBA) crosslinker was investigated at 60 °C for thermal initiators and ambient temperature for redox initiators. The crosslinked PNIPAM plays a key role as thermal-triggered gatekeepers with high loading efficiency and precise release of a model active compound, Nile Blue A (NB). Below the volume phase transition temperature (TVPT), the gatekeepers possess a swollen conformation to block the pores and store NB within the cavities. Above its TVPT, the chains rearrange, allowing gate opening and a rapid and constant release rate of the compound until completion. A precise “on–off” switchable release efficiency of PNIPAM@RS100 was demonstrated by changing the temperatures to 4 and 40 °C. The materials are a promising candidate for controlled drug delivery systems with a precise and easy triggering mechanism at the body temperature for effective treatments.