Controlled long-term sustained release of poly(lactic acid) composite microspheres with dual-responsive cellulose nanocrystals

Abstract

Recently, polymer composite microspheres have attracted substantial attention due to their excellent biodegradable and controlled long-term release characteristics. However, it remains a major challenge to produce polymer microspheres with controlled properties and customizable drug release. To achieve controlled long-term sustained release, polylactide composite microspheres (PLA-C) with dual-responsive cellulose nanocrystals (C-PMA) were engineered by radical polymerization and double emulsion (W/O/W) solvent evaporation. The C-PMA nanoparticles are obtained by grafting poly[2-(N,N-dimethyl amino)ethyl methacrylate] (PDMAEMA) onto cellulose nanocrystals (CNCs), which not only possess the advantages of CNCs but also inherit the excellent temperature and pH responsiveness of PDMAEMA, and used as a dual functional nano reinforcement in polylactic acid microspheres. As expected, 5 wt% C-PMA enhanced the crystallization and hydrophilic properties of PLA-C microspheres. Furthermore, by incorporating the dual-responsive C-PMA nanoparticles, controlled and long-term sustained release behavior of composite microspheres could be achieved. The cumulative release profiles of PLA-C₂₀ composite microspheres loaded with tetracycline hydrochloride (TCH) exhibited low levels of drug release at pH = 7.4 and 8, while at lower pH (5.0) and higher temperatures (43 °C), the drug release rate was significantly accelerated, and the cumulative drug release rate reached 82%, demonstrating a temperature and pH dual-responsive controlled drug release capability of the composite microspheres. Moreover, four drug release kinetic models (zero-order, first-order, Higuchi, and Korsmeyer-Peppas) are presented different drug release mechanisms of dual-responsive PLA-C microspheres. This indicates the dual-responsive PLA-C composite microspheres with potential multifunctional drug delivery systems for promising medical applications.