Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats.

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam's late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110-220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg-1 of MLX and 1 or 4 mg·kg-1 of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C18) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (Cmax) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from 'zero' to infinity (AUC0-∞), half-life (t1/2ß), and mean resident time (MRT) of 1 mg·kg-1 of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg-1 of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects.

Effect of Telmisartan on Arsenic-Induced (Sub-chronic) Perturbations in Redox Homeostasis, Pro-inflammatory Cascade and Aortic Dysfunction in Wistar Rats.

An experimental study was conducted in male Wistar rats to explore the antioxidant potential of telmisartan (an AT1 receptor blocker) to overcome arsenic ('As')-induced perturbations in redox homeostasis pro-inflammatory cytokines, prostaglandin-E2 levels and aortic dysfunction in Wistar rats. Wistar rats were randomly divided into four groups of six each. Group-I served as untreated control, while group-II received sodium (meta) arsenite (NaAsO2) (10 mg/kg b.wt. p.o) for a period of 60 days. Experimental rats in group-III received treatment similar to group-II, but in addition received telmisartan (with 1% aqueous solution of Tween 80) @ 10 mg/kg b.wt. (p.o) for a similar duration, while rats in group-IV received telmisartan alone. Arsenic exposure resulted in significant (p < 0.05) elevation in the levels of superoxide anion ([Formula: see text]) radicals (control: 768.20 ± 126.77 vs group-II: 1232.75 ± 97.85 pmol of NBT reduced/min/mg protein). Telmisartan administration showed significant (p < 0.05) reduction in [Formula: see text] generation (815.34 ± 43.41 pmol of NBT reduced/min/mg protein). Sub-chronic exposure to 'As' significantly (p < 0.05) decreased the activities of SOD, CAT, GPx and GR activity and GSH levels in the aorta, thus induced lipid peroxidation (LPO) measured as measured in terms of thiobarbituric acid reactive substances (TBARS) called as malondialdehyde (MDA). However, the administration of telmisartan effectively countered the LPO (24.03 ± 1.18 nmol of MDA/g) on account of restoring the levels of aforesaid antioxidant defense system. Telmisartan administration effectively attenuated the 'As'-induced surge in pro-inflammatory cytokines (viz., IL-1ß, IL-6 and TNF-α) levels, as well as countered the activity of cyclooxygenase (COX2) as indicated by a significant (p < 0.05) decrease in PGE2 level in the aorta. In addition to it, there was a significant (p < 0.05) decrease in plasma angiotensin II (Ang-II) levels in experimental rats receiving telmisartan. Quantitative RT-PCR studies revealed that sub-chronic exposure to 'As' upregulated the Nox2 mRNA expression, but there was a 1.2-fold reduction in expression level upon co-administration of telmisartan. Histopathological examination revealed marked recovery from 'As'-induced disruption of tunica adventitia and loss of connective tissue in experimental rats receiving telmisartan. The study concludes that telmisartan can overcome aortic dysfunction induced by sub-chronic exposure to arsenic through drinking water in experimental rats through restoration of redox balance, attenuation of pro-inflammatory cytokines and mediators and downregulation of Nox2 mRNA expression.

Anticancer efficacy of 6-thioguanine loaded chitosan nanoparticles with or without curcumin.

6-Thioguanine encapsulated chitosan nanoparticles (6-TG-CNPs) has formulated by the ionic-gelation method. Morphologically, the 6-TG-CNPs were spherical and showed mean size, PDI, zeta potential, and entrapment efficiency of 261.63 ± 6.01 nm, 0.34 ± 0.10, +15.97 ± 0.46 mV and 44.27%, respectively. The IR spectra confirmed the 6-TG complex with chitosan. The in vitro drug release profile of 6-TG-CNPs revealed an increase in sustained-release (91.40 ± 1.08% at 48 h) at pH 4.8 compared to less sustained-release (73.96 ± 1.12% at 48 h) at pH 7.4. The MTT assay was conducted on MCF-7 and PA-1 cell lines at 48 h incubation to determine % cell viability. The IC50 values of 6-TG, 6-TG-CNPs, and curcumin for MCF-7 were 23.09, 17.82, and 15.73 µM, respectively. Likewise, IC50 values of 6-TG, 6-TG-CNPs, and curcumin for PA-1 were 5.81, 3.92, and 12.89 µM, respectively. A combination of 6-TG-CNPs (IC25) with curcumin (IC25) on PA-1 and MCF-7 showed % cell viability of 43.67 ± 0.02 and 49.77 ± 0.05, respectively. The in vitro cytotoxicity potential in terms of % cell viability, early apoptosis, G2/M phase arrest, and DNA demethylating activity of 6-TG-CNPs alone and combination with curcumin proved to be more effective than that of 6-TG on PA-1 cells.