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 bioactivity, encapsulation in PLGA-PEG nanoparticles was studied. The effect on nanoparticles properties of the surfactant type (Pluronic® 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® 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 μg/mL and higher than 75% for 400.0 μg/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.