METHODS: Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes.

Materials and Methods: Biodegradable polymeric microneedle arrays were fabricated out of poly lactic-co-glycolic acid (PLGA) using the micromolding technique under aseptic conditions, and the morphology of the microneedles was characterized using light microscopy. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to rule out drug-polymer interactions. Standard procedures were used to analyze the prepared microneedle arrays for in vitro drug release and to perform a microneedle insertion test. Enzyme-linked immunosorbent assay was used to quantify rHuKGF.

Results: The PLGA polymer was safe for use in the fabrication of rHuKGF microneedles as there was no interaction between the drug and the polymer. The fabricated rHuKGF microneedle arrays had fully formed microneedles with a height of 600 µm and a base of 300 µm. The drug from the microneedle patch was released in vitro within 30 minutes. The strength of the microneedles in the patch was good, as they were able to reach a depth of 381±3.56 µm into parafilm without any structural change or fracture.

OBJECTIVES: The present study was aimed to fabricate the capecitabine as smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.

METHODS: The smart pH sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.

RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. Capecitabine loading was ranged from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%) was seen at pH 7.4. Based upon regression coefficient R2 (0.96 - 0.99) best fit model was zero order. The extensive toxicity evaluations evidenced good safety profile with no signs of oral, dermal or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.

PRINCIPAL FINDINGS: The serum antigen concentration-time profile of the N. sumatrana venom and its major toxins injected intravenously fitted a two-compartment model of pharmacokinetics. The systemic clearance (91.3 ml/h), terminal phase half-life (13.6 h) and systemic bioavailability (41.9%) of N. sumatrana venom injected intramuscularly were similar to those of N. sputatrix venom determined in an earlier study. The venom neurotoxin and cardiotoxin reached their peak concentrations within 30 min following intramuscular injection, relatively faster than the phospholipase A2 and whole venom (Tmax=2 h and 1 h, respectively). Rapid absorption of the neurotoxin and cardiotoxin from the injection site into systemic circulation indicates fast onsets of action of these principal toxins that are responsible for the early systemic manifestation of envenoming. The more prominent role of the neurotoxin in N. sumatrana systemic envenoming is further supported by its significantly higher intramuscular bioavailability (Fi.m.=81.5%) compared to that of the phospholipase A2 (Fi.m.=68.6%) or cardiotoxin (Fi.m.=45.6%). The incomplete absorption of the phospholipase A2 and cardiotoxin may infer the toxins' affinities for tissues at the injection site and their pathological roles in local tissue damages through synergistic interactions.