Polymeric biomaterials have found widespread applications in nanomedicine, and poly(lactide-co-glycolide), (PLGA) in particular has been successfully implemented in numerous drug delivery formulations due to its synthetic malleability and biocompatibility. However, the need for preconception in these formulations is increasing, and this can be achieved by selection and elimination of design variables in order for these systems to be tailored for their specific applications. The starting materials and preparation methods have been shown to influence various parameters of PLGA-based nanocarriers and their implementation in drug delivery systems, while the implementation of computational simulations as a component of formulation studies can provide valuable information on their characteristics. This review provides a critical summary of the synthesis and applications of PLGA-based systems in bio-medicine and outlines experimental and computational design considerations of these systems.

Poor circulation stability and inadequate cell membrane penetration are significant impediments in the implementation of nanocarriers as delivery systems for therapeutic agents with low bioavailability. This research discusses the fabrication of a biocompatible poly(lactide-co-glycolide) (PLGA) based nanocarrier with cationic and hydrophilic surface properties provided by natural polymer chitosan and coating polymer polyethylene glycol (PEG) for the entrapment of the hydrophobic drug disulfiram. The traditional emulsification solvent evaporation method was compared to a microfluidics-based method of fabrication, with the optimisation of the parameters for each method, and the PEGylation densities on the experimental nanoparticle formulations were varied. The size and surface properties of the intermediates and products were characterised and compared by dynamic light scattering, scanning electron microscopy and X-ray diffraction, while the thermal properties were investigated using thermogravimetric analysis and differential scanning calorimetry. Results showed optimal particle properties with an intermediate PEG density and a positive surface charge for greater biocompatibility, with nanoparticle surface characteristics shielding physical interaction of the entrapped drug with the exterior. The formulations prepared using the microfluidic method displayed superior surface charge, entrapment and drug release properties. The final system shows potential as a component of a biocompatible nanocarrier for poorly soluble drugs.

Nanoparticles are designed to entrap drugs at a high concentration, escape clearance by the immune system, be selectively taken up by cancer cells, and release bioactives in a rate-modulated manner. In this study, quercetin-loaded PLGA nanoparticles were prepared and optimized to determine whether coating with chitosan would increase the cellular uptake of the nanoparticles and if the targeting ability of folic acid as a ligand can provide selective toxicity and enhanced uptake in model LnCap prostate cancer cells, which express high levels of the receptor prostate-specific membrane antigen (PSMA), compared to PC-3 cells, that have relatively low PSMA expression. A design of experiments approach was used to optimize the PLGA nanoparticles to have the maximum quercetin loading, optimal cationic charge, and folic acid coating. We examined the in vitro release of quercetin and comparative cytotoxicity and cellular uptake of the optimized PLGA nanoparticles and revealed that the targeted nano-system provided sustained, pH-dependent quercetin release, and higher cytotoxicity and cellular uptake, compared to the non-targeted nano-system on LnCap cells. There was no significant difference in the cytotoxicity or cellular uptake between the targeted and non-targeted nano-systems on PC-3 cells (featured by low levels of PSMA), pointing to a PSMA-specific mechanism of action of the targeted nano-system. The findings suggest that the nano-system can be used as an efficient nanocarrier for the targeted delivery and release of quercetin (and other similar chemotherapeutics) against prostate cancer cells.