Category: Formulation and Quality
Purpose: Combining nanocarriers with stimuli-sensitive hydrogels represents an emerging plethora of therapeutics. In this context, attempts to manage intra-articular disorders namely rheumatoid arthritis (RA) via injectable smart hydrogels have been developed.
Methods: Variable approaches comprising disease-modifying anti-rheumatics (e.g., methotrexate and prednisolone among others), polymer- and lipid-based nanoparticles, pH- and thermosensitive hydrogels were allocated. Nanocarriers were further surface coated prior to their incorporation in stimuli-responsive hydrogels to impart targetability and synergy. Formulation variables in terms of nanocarrier composition, coating material, hydrogel type were thoroughly investigated. Formulations (drug-loaded hydrogels and drug-loaded nanoparticles-in-hydrogels, in presence and absence of surface coating) have been evaluated in vitro in terms of thermogelling time and temperature, thermoreversibility, syringeability as well as drug entrapment and release. As a proof of concept, optimized hydrogels were injected in vivo in RA-induced rats. The joint healing ability was assessed via histopathological examination and serum immunomodulatory responses.
Results: Nanoparticulate carriers provided high encapsulation capacity of the payload. Drug nanoencapsulation prior to incorporation in the hydrogel ensured distinct sustained drug release over 1-2 months. Loaded hydrogels showed thermogelling behaviour at 37°C within 1-4 min with 300-400 times increase in viscosity according to composition. In vivo studies revealed perfect joint healing in case of nano-in-hydrogel formulation, whereby coated particles showed a non-negligible synergistic effect in addition to reduced TNF-alfa levels relative to either the free drug or loaded hydrogels.
Conclusion: The study highlights the potential of nano-in-smart hydrogels to provide effective levels of the payload over prolonged periods directly at the target site, thus, suggesting a promising platform for the local treatment of joint disorders.