Background:
Methotrexate (MTX) is the representative drug among the disease-modifying anti-rheumatic drugs.
But the conventional treatment with MTX showed many limitations and side effects.
Objective:
To 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.
Methods:
Firstly, 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.
Results:
This 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.
Conclusion:
This targeting drug delivery system laid a promising foundation for the treatment of RA.
FORMULATION OF SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM OF BOVINE SERUM ALBUMIN USING HLB (HYDROPHILIC-LYPOPHILIC BALANCE) APPROACH
