Development of Tofacitinib Loaded pH-Responsive Chitosan/Mucin Based Hydrogel Microparticles: In-Vitro Characterization and Toxicological Screening

Abstract

Tofacitinib is an antirheumatic drug characterized by a short half-life and poor permeability, which necessitates the development of sustained release formulation with enhanced permeability potential. To achieve this goal, the free radical polymerization technique was employed to develop mucin/chitosan copolymer methacrylic acid (MU-CHI-Co-Poly (MAA))-based hydrogel microparticles. The developed hydrogel microparticles were characterized for EDX, FTIR, DSC, TGA, X-ray diffraction, SEM, drug loading; equilibrium swelling (%), in vitro drug release, sol–gel (%) studies, size and zeta potential, permeation, anti-arthritic activities, and acute oral toxicity studies. FTIR studies revealed the incorporation of the ingredients into the polymeric network, while EDX studies depicted the successful loading of tofacitinib into the network. The thermal analysis confirmed the heat stability of the system. SEM analysis displayed the porous structure of the hydrogels. Gel fraction showed an increasing tendency (74–98%) upon increasing the concentrations of the formulation ingredients. Formulations coated with Eudragit (2% w/w) and sodium lauryl sulfate (1% w/v) showed increased permeability. The formulations equilibrium swelling (%) increased (78–93%) at pH 7.4. Maximum drug loading and release (%) of (55.62–80.52%) and (78.02–90.56%), respectively, were noticed at pH 7.4, where the developed microparticles followed zero-order kinetics with case II transport. Anti-inflammatory studies revealed a significant dose-dependent decrease in paw edema in the rats. Oral toxicity studies confirmed the biocompatibility and non-toxicity of the formulated network. Thus, the developed pH-responsive hydrogel microparticles seem to have the potential to enhance permeability and control the delivery of tofacitinib for the management of rheumatoid arthritis.

Formulation and Evaluation of Polysaccharide Microparticles for the Controlled Release of Propranolol Hydrochloride

“…Changes in the spherical shape can also be caused by the adhesive nature of chitosan and the type of substrate on which the drying process was carried out [ 29 , 30 ]. However, the presence of porous surfaces in coated microparticles had a significant effect on water retention and uptake of physiological media, which consequently improved swelling and affected drug release [ 50 ].…”

Polymeric Hydrogels and Nanogels: Classification, Development and Pharmaceutical Applications

“…It is available as high, medium, and low molecular-weight chitosan. This polymer is cationic, contains nitrogen in its chemical structure, and has ability to form polyelectrolyte complexes [62]. It becomes water soluble by forming carboxylate salts like acetate, citrate, formate, malate, glycolate, pyruvate, lactate, and ascorbate.…”

Local and Sustained Baricitinib Delivery to the Skin through Injectable Hydrogels Containing Reversible Thioimidate Adducts

“…[8,14] Previous research delivering JAK inhibitors from hydrogels only showed release over a few days. [15][16][17][18] A notable example showed metalloprotease-triggered delivery of tofacitinib for atopic dermatitis in vitro from a polyethylene glycol hydrogel, but with release of ≈40% at 48 h. [19] Despite these illustrations of controlled release, extending release for additional days and even weeks is desired, particularly to avoid the need for repeated administrations where compliance is a major barrier to use and clinical translation.…”