# Synthesizing porous nanospheres with highly efficient drug loading and sustained release through a thermal-controlled continuous stirred-tank reactor cascade

## TL;DR

Researchers developed a new method to create nanospheres that can hold more drugs and release them slowly, using a temperature-controlled system that speeds up production.

## Contribution

The novel thermal-controlled CSTR cascade enables core-loading of drugs in nanospheres, improving drug loading and sustained release.

## Key findings

- The CSTR cascade method produces PLGA nanospheres with high cyclosporin A loading capacity.
- The nanospheres enable sustained drug release through PLGA matrix degradation.
- Synthesis time is reduced from hours to 40 minutes using the CSTR approach.

## Abstract

Nanospheres hold great promise for drug delivery but face challenges in achieving both high drug loading and sustained release. Here, we present a novel approach to produce porous cyclosporin A-loaded poly(lactic-co-glycolic acid) (PLGA) nanospheres via a thermal-controlled continuous stirred-tank reactor (CSTR) cascade, featuring rapid solidification of nanoemulsion droplets. This process traps more drug molecules in the nanosphere core by limiting their diffusion towards the surface and surrounding medium, resulting in a core-loaded structure. The resulting PLGA nanospheres exhibit a high cyclosporin A loading capacity and enable sustained drug release through the hydrolytic degradation of the PLGA matrix. Moreover, the total synthesis time is reduced from several hours to 40 min. The CSTR assisted manufacturing approach offers an efficient route for engineering nanospheres with high drug payloads and improved release kinetics, with broad potential for nanomedicine manufacturing.

Advancing drug-loading efficiency and sustained release in PLGA nanospheres through a core-loading strategy, enabled by an engineering-optimized, temperature-controlled CSTR cascade for continuous production. Created with Biorender.com.