Thermo-responsive release of diclofenac sodium from poly (ε-caprolactone)/glyceryl trilaurate co-continuous composite prepared by heat treatment

Abstract

Nowadays, it is still a tough challenge to prepare thermo-responsive drug delivery system without the use of poly(N-isopropylacrylamide) (PNIAPAM) and its derivatives. Herein, we attempted to fabricate a novel co-continuous composite with thermo-responsive drug release behavior induced by the phase transition of dispersed phase. Poly (ϵ-caprolactone) (PCL) scaffold with connected porous structure was prepared first, followed by the introduce and impregnating of diclofenac sodium/glyceryl trilaurate (DS/C12) hot melt mixture. After solidification at 25 °C, PCL/C12 composites with co-continuous structure were obtained. The connected porous structure of PCL scaffold and morphology of PCL/C12 composites were confirmed by scanning electron microscope. The thermo-responsive drug release mechanism of PCL/C12 composites was investigated by differential scanning calorimeter and two-dimensional infrared correlation spectroscopy. The results indicated that the temperature of onset melting and melting point of C12 was about 41.5 °C and 47.5 °C, respectively. When the temperature was switched from 37 °C to 45 °C, C12 underwent a melt transition, and the regular aggregation of C12 molecular chain was disrupted, accelerating the release of DS. The in vitro release results presented that PCL/C12 composites could achieve on-off controlled release of DS under alternative temperature of 45 °C and 37 °C. According to the comprehensive test results, this PCL/C12 composites should have promising application in bone tissue engineering. Schematic diagram illustrating of the preparation of poly (ϵ-caprolactone)/glyceryl trilaurate (PCL/C12) co-continuous composite (a) and its on-off controlled release behavior of diclofenac sodium (DS) under alternative temperature of 45 °C and 37 °C (b and c). • Poly (ϵ-caprolactone)/glyceryl trilaurate (PCL/C12) co-continuous composite was fabricated. • PCL/C12 composite achieved on-off controlled release of diclofenac sodium under alternative temperature of 45 °C and 37 °C. • The controlled drug release behavior of PCL/C12 composite was induced by the phase transition of C12. • This thermo-responsive composite was prepared without the use of poly(N-isopropylacrylamide) and its derivatives. • This work provided a promising strategy and method for the preparation of thermo-responsive drug delivery systems.