Polymeric Microspheres with High Mass Fraction of Therapeutics Enabled by the Manipulation of Kinetics Factor During Emulsion Droplet Solidification

Abstract High drug‐loaded polymeric microspheres hold promise in biomedical fields due to reduced excipient administration, minimized side effects, and enhanced therapeutical efficacy. Although thermodynamic factors like drug‐carrier material compatibility are well‐known to influence the drug loading capacity of microspheres, they fail to explain the huge difference in drug loading degree observed for polymers and drugs with similar interactions. Here, based on the droplet microfluidic platform, the single droplet solidification process is investigated. The results indicated that amorphous polymers can hinder drug diffusion during droplet solidification compared to crystalline polymers, resulting in a higher drug loading degree. Next, this principle is applied to improve the drug loading capability of crystalline polymers (polycaprolactone (PCL) and poly(L‐lactide) (PLLA)) by random co‐polymerization (poly(caprolactone‐co‐L‐lactide) (PCL‐PLLA)), achieving 6.2–22.2 times increased drug loading degree. Moreover, PCL‐PLLA microspheres with a high content of indomethacin exhibited superior therapeutical efficacy in the treatment of gout arthritis. Overall, these results offer insights into the impact of polymer crystallization on droplet solidification kinetics, which consequently affects the drug loading capacity. These findings provide guidelines for the development of polymers for efficient drug encapsulation.