Preparation and evaluation of PLGA-PEG/Gusperimus nanoparticles as a controlled delivery anti-inflammatory drug

Gusperimus is an immunosuppressive drug used to control autoimmune diseases and prevent rejection in organ transplantation. It has a high-water solubility leading to poor intracellular permeability, rapid enzymatic degradation, and clearance. To achieve controlled delivery of Gusperimus and protect its stability and bioac-tivity, encapsulation in PLGA-PEG nanoparticles was studied. The effect on nanoparticles properties of the surfactant type (Pluronic (R) F127, P84, and F108) and polymer concentration (0.2% and 1.7% w/v) used for their preparation was evaluated. The system prepared with 1.7% w/v PLGA-PEG and 1% w/v Pluronic (R) F127 was selected to encapsulate Gusperimus since it provides the smallest particle size and higher colloidal stability. The nanoparticles showed an encapsulation efficiency and a load capacity of 82.8% and 1.48%, respectively. In vitro release showed a total release of 19% after 36 h. PLGA-PEG/Gusperimus nanoparticles were evaluated in vitro to determine their cytotoxicity, cellular uptake, and anti-inflammatory activity in mouse macrophages. They showed no-cytotoxicity for J774A.1 macrophages with 100% viability, for concentrations up to 50 mu g/mL and higher than 75% for 400.0 mu g/mL. PLGA-PEG/Gusperimus nanoparticles were taken up by macrophages and exerted anti-inflammatory effects as it is indicated by nitric oxide reduction and cytokine suppression in LPS-induced inflammatory macrophages model.

Automated summary

In this study, the encapsulation of Gusperimus in PLGA-PEG nanoparticles was investigated to achieve controlled release and protect its stability and bioactivity. The effects of different surfactants and polymer concentrations on the properties of the nanoparticles were evaluated. The results showed that the system prepared with 1.7% w/v PLGA-PEG and 1% w/v Pluronic (R) F127 had the smallest particle size and higher colloidal stability. The nanoparticles exhibited high encapsulation efficiency and load capacity, as well as anti-inflammatory effects in macrophages.