Drug release from PLGA microspheres: recent advances in preparation, mechanism, and modification

Cancer is a leading cause of death worldwide, and new methods for quick diagnosis and management are essential to reduce mortality rates. Microspheres have shown great potential in cancer diagnosis and treatment due to their unique structural, mechanical, physiological, and pharmacokinetic properties Microspheres can be used as drug carriers, packaging or binding therapeutic compounds and delivering them to targeting tissues with greater precision and sustained release. PLGA is an FDA-approved polymer, commonly used in the fabrication of drug-loaded carriers, and has been employed in cancer therapy. The current review is focused on the new development of the release features of anticancer drugs, which are loaded into PLGA-based microspheres. Preparation method of PLGA microsphere: Single emulsification a straightforward and quick method, but often results in wide particle size dispersion and poor entrapment effectiveness. Double emulsification, Electrospray, Spray drying, Polymer phase separation, In situ forming implants a less invasive option, suitable for encapsulation of sensitive drug molecules, Microfluidic technology which produces highly regulated and homogeneous microspheres. and it has been proven to transport anticancer treatment drugs. The positive charge of PLGA may aid the electrostatic interaction of microspheres with negatively charged receptors on tissues or cells, increasing the residence period of microspheres at the target site and providing a proper release of drugs. The incorporation of molecules and drugs in PLGA matrices leads to drug-encapsulated microspheres, providing a sustained release drug delivery platform. Prediction of drug release from PLGA microspheres: Zero-order release, First-order release, Higuchi release, Korsmeyer-Peppas model, Hixson-Crowell model, Weibull model Mechanisms of controlled drug release from PLGA‑based microspheres: Osmosis and osmotic‑induced release, Diffusion through PLGA network, Diffusion through pores, Swelling and water uptake which hydration of the polymer causes matrix volume change, lowering the glass transition temperature, and increasing drug diffusion and Hydrolysis and erosion. Factors that influence drug release from PLGA‑based microspheres: LA/GA ratio, MW, terminal group, synthetic parameters, degradation kinetics, mechanical, rheological, and thermal characteristics, Surface modification, Morphology and size of microspheres and water absorption influence drug release profile of PLGA-based microspheres In vitro techniques used to evaluate drug release from PLGA microspheres: flow-through cell, dialysis, and sample-and-separate methods In vitro release profiles may not accurately predict in vivo release due to differences in biological (such as inflammatory response, lipids, enzymes, and organic amines) and physiochemical properties (such as pH, fluid volume, and convection). Optimizing average MW and MW distribution of PLGA is necessary to control burst release. Particle size, drug loading , Surface modification, morphology, and MW of PLGA affect in vitro release pattern Much research has been performed for in vitro anticancer drug release testing and the parameters that influence the release to provide insight into the in vivo performance of formulations. Despite the advantages of PLGA microspheres, no products have reached the market yet, and surface modification can affect clinical performance compared to in vitro. Future initiatives include enhancing tumor microenvironment delivery techniques, optimizing the release mechanism of formulations, and modification of their composition. The fabrication of PLGA-based nanospheres is another approach that can enhance the performance of drug release.

کلیدواژه ها:

Microspheres ، PLGA ، Nanotechnology ، Drug delivery ، Anticancer drug