Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable and biocompatible copolymer in drug delivery systems (DDSs). In this article, we highlight the critical physicochemical properties of PLGA, including its molecular weight, intrinsic viscosity, monomer ratio, blockiness, and end caps, that significantly influence drug release profiles and degradation times. This review also covers the extensive literature on the application of PLGA in delivering small-molecule drugs, proteins, peptides, antibiotics, and antiviral drugs. Furthermore, we discuss the role of PLGA-based DDSs in the treating various diseases, including cancer, neurological disorders, pain, and inflammation. The incorporation of drugs into PLGA nanoparticles and microspheres has been shown to enhance their therapeutic efficacy, reduce toxicity, and improve patient compliance. Overall, PLGA-based DDSs holds great promise for the advancement of the treatment and management of multiple chronic conditions.

Accurately measuring drug and its release kinetics in both in vitro and in vivo environments is crucial for enhancing therapeutic effectiveness while minimizing potential side effects. Nevertheless, the real-time visualization of drug release from microspheres to monitor potential overdoses remains a challenge. The primary objective of this investigation was to employ fluorescence imaging for the real-time monitoring of drug release from microspheres in vitro, thereby simplifying the laborious analysis associated with the detection of drug release. Two distinct varieties of microspheres were fabricated, each encapsulating different drugs within PLGA polymers. Cy5 was selected as the donor, and Cy7 was selected as the acceptor for visualization and quantification of the facilitated microsphere drug release through the application of the fluorescence resonance energy transfer (FRET) principle. The findings from the in vitro experiments indicate a correlation between the FRET fluorescence alterations and the drug release profiles of the microspheres.