Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis.

This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1ß level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.

Highlighting the impact of chitosan on the development of gastroretentive drug delivery systems.

The development of gastroretentive systems have been growing lately due to the high demand for carriers that increase drug bioavailability and therapeutic effectiveness after oral administration. Most of systems reported up to now are based on chitosan (CS) due to its peculiar properties, such as cationic nature, biodegradability, biocompatibility and important mucoadhesiveness, which make CS a promising biopolymer to design effective gastroretentive systems. In light of this, we reported in this review the CS versatility to fabricate different types of nano- and microstructured gastroretentive systems. For a better understanding of the gastric retention mechanisms, we highlighted expandable, density-based, magnetic, mucoadhesive and superporous systems. The biological and chemical properties of CS, anatomophysiological aspects related to gastrointestinal tract (GIT) and some applications of these systems are also described here. Overall, this review may assist researchers to explore new strategies to design safe and efficient gastroretentive systems in order to popularize them in the treatment of diseases and clinical practices.