Dual sustained-release PTMC/PCL porous microspheres for lipid-soluble drugs

It is still a considerable research challenge to design biodegradable drug delivery systems that efficiently transport lipid-soluble drugs with controlled release. In the present study, a microsphere delivery system, γ-cyclodextrin (γ-CD)/glutathione (GSH)-atorvastatin (AT) fibrous nanoparticles (γ-CD/GSH-AT FNs) loaded polytrimethylene carbonate (PTMC)/polycaprolactone (PCL) microspheres (PTMC/PCL/γ-CD/GSH-AT MPs), was constructed through an exquisite method. The results show that a large number of γ-CD/GSH-AT FNs can be encapsulated during the formation of microspheres and released in a controllable manner. Notably, the high dispersibility and drug loading of FNs can load with lipid-soluble drugs and protect the drugs from the solvent during microsphere preparation. FNs and MPs can achieve dual release. First, with the degradation of the microspheres, the encapsulated FNs were gradually released into the local microenvironment. Subsequently, the FNs began to dissolve and release the loaded AT over a period of more than 3 days. Therefore, the dual sustained-release drug delivery system can maintain the blood drug concentration for a longer time and reduce the number of administrations and the side effects of the drug. This study provides new ideas for the on-demand manufacture of controllable degradable drug delivery platforms to treat diseases. • We developed a novel PTMC/PCL-based porous microsphere with dual release function. • The microspheres can effectively load γ-CD/GSH-AT fibrous nanoparticles containing lipid-soluble drugs. • The dual controlled-release microspheres can perform sequential release of nanoparticles and drugs. • The dual controlled-release microspheres can improve the bioavailability of lipid-soluble drugs. • Fibrous nanoparticles have excellent biocompatibility and sufficient pharmacological activity.