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Background: Pyrazinamide is a Biopharmaceutical Classification System class III antibiotic indicated for active tuberculosis. Methods: In the present work, pyrazinamide-loaded biodegradable polymeric nanoparticles (PNPs) based dry powder inhaler were developed using the double emulsion solvent evaporation technique and optimized using design of experiments to provide direct pulmonary administration with minimal side effects. Batches were characterized for various physicochemical and aerosol performance properties. Results: Optimized batch exhibited particle size of 284.5 nm, % entrapment efficiency of 71.82%, polydispersibility index of 0.487, zeta potential of −17.23 mV, and in vitro drug release at 4 hours of 79.01%. Spray-dried PNPs were evaluated for drug content, in vitro drug release, and kinetics. The particle mass median aerodynamic diameter was within the alveolar region's range (2.910 μm). In the trachea and lung, there was a 2.5- and 1.2-fold increase in in vivo deposition with respect to pure drug deposition, respectively. In vitro drug uptake findings showed that alveolar macrophages with pyrazinamide PNPs had a considerably higher drug concentration. Furthermore, accelerated stability studies were carried out for the optimized batch. Results indicated no significant change in the evaluation parameters, which showed stability of the formulation for at least a 6-month period. Conclusion: PNPs prepared using biodegradable polymers exhibited efficient pulmonary drug delivery with decent stability. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The present investigation was undertaken to develop a psoriatic-like skin inflammation rat model using imiquimod (IMQ) as an inducing agent. MATERIALS AND METHODS: The hairs of the back dorsal portion of the Wistar rats were removed and 80, 100, and 120 mg of IMQ cream (5% w/w) for 10 consecutive days was applied to different groups of rats. Further, psoriasis area severity index was used for calculating the psoriatic score, which included scoring of erythema, scaling, and thickening. Various biochemical parameters, pro-inflammatory cytokines, vascular endothelial growth factor (VEGF), and histopathological examination were also performed. RESULTS: The results demonstrated signs of erythema, scaling, and thickening on group applied with 120 mg and 100 mg of IMQ along with ear thickening. Biochemical evaluation revealed a significant increase in the granulation tissue weight followed by significant decrease in the levels of collagen and hexosamine. The antioxidant parameters superoxide dismutase and catalase were found to decline, while nitric oxide and lipid peroxidation were significantly elevated in skin lesions, also supported by increased pro-inflammatory cytokines expression, i.e., interleukin (IL)-1 β, IL-6, IL-17, tumor necrosis factor-α, and VEGF. Histopathological studies revealed a disturbed natural structure along with increased epidermal proliferation, abnormal differentiation with increased number of keratinocytes in the psoriatic skin tissue. CONCLUSION: From the overall study, we have successfully developed a psoriatic-like skin inflammation rat model for the first time on Wistar strain using IMQ as an inducing agent. [ABSTRACT FROM AUTHOR]