Prodrug-based nanomedicines for rheumatoid arthritis

Abstract

Most antirheumatic drugs with high toxicity exhibit a narrow therapeutic window due to their nonspecific distribution in the body, leading to undesirable side effects and reduced patient compliance. To in response to these challenges, prodrug-based nanoparticulate drug delivery systems (PNDDS), which combines prodrug strategy and nanotechnology into a single system, resulting their many advantages, including stability for prodrug structure, the higher drug loading capacity of the system, improving the target activity and bioavailability, and reducing their untoward effects. PNDDS have gained attention as a method for relieving arthralgia syndrome of rheumatoid arthritis in recent years. This article systematically reviews prodrug-based nanocarriers for rheumatism treatment, including Nano systems based on prodrug-encapsulated nanomedicines and conjugate-based nanomedicines. It provides a new direction for the clinical treatment of rheumatoid arthritis.

Keywords: Drug delivery systems; Prodrug-based nanoparticulate; Rheumatoid arthritis; Targeted therapy.

Fig. 1

The distinction of microenvironment between healthy joint and RA joint, and the principle of endogenous stimuli-responsive materials releasing drugs

Fig. 2

The graphical abstract of prodrug-based nanomedicines for RA

Fig. 3

Diagram of the synthesis of DEX/siRNA-loaded polymeric micelles. Schematic illustration of siRNA/DOTAP nanocomplex followed by the encapsulation of DXP and siRNA/DOTAP nanocomplex in PLGA-PEG-based polymeric micelles. DOTAP: 1,2-Dioleoyl-3-trimethylammonium-propane

Fig. 4

The chemical structure and activation of prodrugs (Adapted from [75, 79]). Dotted line indicates cleavage site. A The prodrug of DS-PVGLIG-Cel release Cel under MMP-2 response. B The prodrug of Abps-tk-Cur release Cur under ROS response. C The prodrug of HA-TK-ART release ART under ROS response

Fig. 5

Some redox and enzyme-responsive conjugate-based nanomedicines. A The design with MMP-2 and ROS dual responses, and the biosynthesis schematic illustration of D&A@Cel; B The ROS-responsive HTA prodrug micelles for co-delivering DEX

Fig. 6

Schematic illustration of actively targeted delivery conjugate-based nanomedicines. A Polymer-based targeted delivery; B Peptides-based targeted delivery; C Protein-based targeted delivery