Current medicinal chemistry | 2021
Preparation and formulation optimization of methotrexate-loaded human serum albumin nanoparticles modified by mannose.
Abstract
BACKGROUND\nMethotrexate (MTX) is the representative drug among the disease-modifying anti-rheumatic drugs. But the conventional treatment with MTX showed many limitations and side effects.\n\n\nOBJECTIVE\nTo strengthen the targeting ability and circulation time of MTX in the treatment of rheumatoid arthritis, the present study focused on developing a novel drug delivery system of methotrexate-loaded human serum albumin nanoparticles (MTX-NPs) modified by mannose, which referred as MTX-M-NPs.\n\n\nMETHODS\nFirstly, mannose-derived carboxylic acid was synthesized and further modified on the surface of MTX-NPs to prepare MTX-M-NPs. The formulation of nanoparticles was optimized by method of central composite design (CCD), with the drug lipid ratio, oil-aqueous ratio, and cholesterol or lecithin weight as the independent variables. The average particle size and encapsulation efficiency were the response variables. Response of different formulations was calculated and the response surface diagram, contour diagram and mathematical equation were used to relate the dependent and independent variables to predict the optimal formula ratio. The uptake of MTX-M-NPs by neutrophils was studied through the laser confocal detection. Further, MTX-M-NPs was subjected to assess the pharmacokinetics profile after intravenous injection with Sprague-Dawley rats.\n\n\nRESULTS\nThis targeting drug delivery system was successfully developed. Results from Nuclear Magnetic Resonance and Fourier Transform Infrared Spectroscopy analysis can verify the successful preparation of this drug delivery system. Based on the optimized formula, MTX-M-NPs was prepared with a particle size of 188.17 ± 1.71 nm and an encapsulation rate of 95.55 ± 0.33%. MTX-M-NPs displayed significantly higher cellular uptake than MTX-NPs. The pharmacokinetic results showed that MTX-M-NPs could prolong the in vivo circulation time of MTX.\n\n\nCONCLUSION\nThis targeting drug delivery system laid a promising foundation for the treatment of RA.