Methotrexate-loaded oil-in-water nanoemulsion formulations were prepared using the high shear homogenization technique. A drug excipient study (ATR-FTIR) was carried out to investigate the compatibility between the drug, the polymers, and its admixtures. The thermal stability of the nanoemulsion formulations was evaluated by subjecting them to a heating and cooling cycle. The prepared nanoemulsion formulations (FNE1 to FNE6) were evaluated for particle size, PDI value, and entrapment efficiency (EE). They were analyzed for morphological information using transmission electron microscopy. The drug (methotrexate)-loaded nanoemulsion formulations (FNE2, FNE4, and FNE6) were then converted into nanoemulsion gel formulations by adding 1% chitosan (polymer) as a gelling agent. The nanoemulsion gel formulations (FNEG2, FNEG4, and FNEG6) were investigated for physicochemical parameters, viscosity, spreadability, extrudability, drug content, and skin irritation. Various penetration enhancers (olive oil, clove, and almond oil) were employed to examine the potency of the prepared nanoemulsion gel formulations. In vitro drug release, ex vivo permeation, skin drug retention, and stability tests were carried out for evaluation of the prepared nanoemulsion gel formulations (FNEG2, FNEG4, and FNEG6). The data obtained from the in vitro study were subjected to the kinetic model, and the Korsemeyer–Peppas model was best fitted to the data. The nanoemulsion gel formulation FNEG6 showed the maximum controlled drug release and followed an anomalous, non-Fickian release mechanism. The use of almond oil in the preparation of the nanoemulsion gel formulation FNEG6 helped the penetration of the drug across stratum corneum and the restructuring of the properties of skin and resulted in a higher penetration and retention of methotrexate in a deeper layer of the skin. The current study concluded that the methotrexate-loaded nanoemulsion gel formulation FNEG6 showed the best optimum release, permeation, and retention results as compared to the available oral tablets’ formulations, followed by a low serum concentration and the maximum drug retention, which is beneficial in treating skin infections and reducing systemic toxicity.

Accumulation of heavy metals in soil and vegetables is presently a challenging environmental concern worldwide. The present study was designed to elucidate heavy metals contamination of vegetables irrigated with domestic wastewater and associated health risks. The study area comprises three zones: Kot Addu, Alipur, and Muzaffargarh. A total of 153 samples of wastewater, topsoil, and vegetables were analyzed for physicochemical parameters and concentration levels of eight metal elements (Cu, Fe, Zn, Mn, Pb, Cd, Ni, and Cr) determined through analytical procedures. The outcome of the present investigation reveals that heavy metal concentrations in wastewater, soil, and vegetables irrigated with wastewater were slightly higher than the WHO-suggested limit. The heavy metals concentration observed in vegetables irrigated with wastewater can be ranked in order of Ni > Mn > Cr > Pb > Cu > Fe > Zn > Cd. Transfer factor (TF), daily ingestion of metals (DIM), and health risk index (HRI) were calculated. Spinach exhibited higher values of transfer factor than cabbage, cauliflower, and radish, which were followed by tinda and carrot. Minimum values of HRI were observed for Cr (0.0109) in almost all of the vegetables ingested by adults and children. Cabbage exhibited higher values of HRI for Pb (4.0656) in adults, followed by cadmium (HRI = 2.993). Minimum values of HRI were calculated for Cd (0.0115; child). Cauliflower exhibited higher values of HRI (5.2768) for Pb in children. Pb, HRI values (4.5902) were observed in adults living in Kot Addu. The results exhibited similar trends of HRI in adults and children living in Muzaffargarh and Alipur.

Level of toxic heavy metal concentration like lead (Pb), chromium (Cr), cadmium (Cd), iron (Fe), copper (Cu), zinc (Zn), and nickel (Ni) in thirty‐six soft and hard organs and their impact on lipid profile of Hypophthalmichthys molitrix and Catla catla fish species inhibiting in Tanda Dam reservoir were investigated. The heavy metal concentrations in water, sediment, and fish of the different regions in the reservoir were determined with atomic absorption spectrophotometer. Lipid profile was carried out by AOAC official methods. The results showed that Pb was dominant among all the heavy metals in six organs, and its maximum concentration of Pb (22.5 mg kg^-1 and 32.9 mg kg^-1) was observed in scales in Hypophthalmichthys molitrix and tail of Catla catla, respectively. The maximum concentrations of Cd were observed in the head, scales, fins, and gills of Catla catla. The bioaccumulation of heavy metals was significantly different at (p ≤ 0.01) within the organs and between the fish species. The lipid concentration was minimum in those organs where the concentrations of heavy metals were maximum. It is clear from the findings that heavy metal accumulation reduces the lipid content of fish. It is inevitable to monitor the Tanda Dam reservoir to safeguard human health.

Hydrogel is one of the most interesting and excellent candidates for oral drug delivery. The current study focuses on formulation development of hydrogels for controlled oral delivery of esomeprazole. The hydrogels were prepared by solution casting method by dissolving polymers in Polyvinyl alcohol (PVA) solution. Calcium alginate, Hydroxyl propyl methylcellulose (HPMC), acrylic acid and chondroitin sulfate were used in the preparation of hydrogels. Fourier transform infrared (FTIR) analysis showed no incompatibilities between drug and excipients used in the preparation of formulations. The hydrogels were characterized for size and surface morphology. Drug encapsulation efficiency was measured by Ultraviolet-visible (UV-VIS) spectroscopy. In vitro release studies were carried out using dissolution apparatus. The formulated hydrogels were then compared with the marketed product in vivo using rabbits. The result indicates that prepared hydrogels have a uniform size with a porous surface. The esomeprazole encapsulation efficiency of the prepared hydrogels was found to be 83.1 ± 2.16%. The esomeprazole-loaded hydrogel formulations showed optimum and Pharmacopeial acceptable range swelling behavior. The release of esomeprazole is controlled for 24 h (85.43 ± 0.32% in 24 h). The swelling and release of drug results make the prepared hydrogels a potential candidate for the controlled delivery of esomeprazole. The release of the drug from prepared hydrogel followed the super case transport-2 mechanism. The in vivo studies showed that prepared hydrogel formulations showed controlled and prolonged release of esomeprazole as compared to drug solution and marketed product. The formulations were kept for stability studies; there was no significant change observed in physical parameters, i.e., (appearance, color change and grittiness) at 40 °C ± 2/75% ± RH. There was a negligible difference in the drug content observed after the stability study suggested that all the formulations are stable under the given conditions for 60 days. The current study provides a valuable perspective on the controlled release profile of Hydroxyl propyl methylcellulose (HPMC) and calcium alginate-based esomeprazole hydrogels.

The physicochemical parameters and heavy metals concentration in the groundwater of the coastal region of Lasbela, Baluchistan were investigated. Cations and anions were determined through ion chromatography. The concentration levels of eight heavy metals (Cr, Cd, Pb, Zn, Fe, Cu, and Mn) in the groundwater were analyzed through the analytical procedures of atomic absorption spectrophotometry. The cations were present in the descending order of magnesium > sodium > calcium > potassium and anions as bicarbonate > sulfate > chloride. Two parameters (bicarbonate and total dissolved solids) were above and other physicochemical indices of groundwater were below the threshold limits of the WHO. Positive correlations of pH and electrical conductivity were observed with cations and anions. The significant positive correlation between sodium and bicarbonate (0.427) indicated the dissolution of carbonate rocks. The concentration of heavy metals (Cu, Cd, Mn, Cr, Pb, Fe, Zn, and Ni) ranged from 0.1 to 0.4, 0.02 to 0.09, 0.04 to 0.9, 0.03 to 0.5, 0.01 to 0.91, 0.05 to 1.30, 0.01 to 0.60, and 0.02 to 0.90 mg/L. The highest concentration of Pb (0.21 mg/L) and Cd (0.16 mg/L) were approximately 20 and 50 times higher than the permissible limits of the WHO. Hierarchical cluster analysis classified the twelve physicochemical parameters into four clusters and the eight heavy metals into seven clusters. Principal component analysis extracted eight latent components for physicochemical properties and heavy metals with eigenvalues greater than 1.0 that had positive loads of fluoride, iron, electrical conductivity, sodium, cadmium, and sulfate. Major pollutants in the groundwater were accounted for by PC 1, and the main factors that affected the water quality were Pb, Cr, and Cu. Fe had a modest impact on the water quality in this region. From the findings, it can be concluded that the coastal groundwater of the region has a higher concentration of heavy metals, which makes it unfit for drinking purposes.