In:
Current Medicinal Chemistry, Bentham Science Publishers Ltd., Vol. 28, No. 24 ( 2021-08-13), p. 5016-5029
Abstract:
Methotrexate (MTX) is the representative drug among the disease-
modifying anti-rheumatic drugs. However, 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 are referred to 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 the 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. The 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 confocal laser detection. Further, MTX-M-NPs were subjected
to assessment of 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 were 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.
Type of Medium:
Online Resource
ISSN:
0929-8673
DOI:
10.2174/0929867328666210118112640
Language:
English
Publisher:
Bentham Science Publishers Ltd.
Publication Date:
2021
SSG:
15,3
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