Enhanced Therapeutic Effect of RGD-Modified Polymeric Micelles Loaded With Low-Dose Methotrexate and Nimesulide on Rheumatoid Arthritis

Theranostics
Yunlong WangZhirong Zhong

Abstract

Angiogenesis plays an essential role in the progression of rheumatoid arthritis (RA). RGD peptide shows high affinity and selectivity for integrin αvβ3, which is one of the most extensively examined target of angiogenesis. Nimesulide could improve the anti-rheumatic profile of methotrexate. But the clinical application was limited due to water-insolubility of both methotrexate and nimesulide and lacking targeting ability. Therefore, this study aimed to design a targeted drug delivery system of micelles mediated by RGD plus the passive targeting of micelles to solve the application problems of methotrexate and nimesulide (M/N), and thus enhance their combined therapeutic effect on RA. Methods: RGD was conjugated with NHS-PEG-PLA to form RGD-PEG-PLA for the preparation of RGD-modified drug-loaded micelles (R-M/N-PMs). The size and zeta potential of micelles were measured by dynamic light scattering. Morphology was detected by transmission electron microscopy. The inhibition effect of R-M/N-PMs on angiogenesis was assessed by the chick chorioallantoic membrane assay. The real-time fluorescence imaging analysis was conducted to examine the in vivo distribution of the fluorescence-labeled R-M/N-PMs. Rats arthritis model induced by F...Continue Reading

Citations

Sep 13, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Thomas EbenhanMike Sathekge
Dec 10, 2020·Expert Opinion on Drug Metabolism & Toxicology·Nagarani ThotakuraKaisar Raza
Apr 20, 2021·Advanced Healthcare Materials·Long ChenHai-Quan Mao
May 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jian LiZhirong Zhong
Jan 1, 2021·ACS Applied Materials & Interfaces·Jiayao LyuZhirong Zhong
Aug 21, 2021·Advanced Healthcare Materials·Jun DaiShixuan Wang

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Methods Mentioned

BETA
fluorescence imaging
dynamic light scattering
transmission electron microscopy
ELISA

Software Mentioned

Image - Pro Plus
GraphPad Prism
NIH
GraphPad

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