Methods: Forty-eight male Sprague Dawley rats were allocated into eight groups of six rats (n = 6): control, CP only (200 mg kg-1), AM only (100 mg kg-1, 300 mg kg-1 and 500 mg kg-1) and CP + AM (100 mg kg-1, 300 mg kg-1 and 500 mg kg-1). Animals were sacrificed after 63 days of treatment and the sperm from the caudal epididymis was taken for sperm analysis.
Results: The body and the reproductive organs weight, sperm count and motility did not differ between CP and other groups (P > 0.05). A significant increase (P < 0.05) in percentage of the dead and abnormal sperm were seen in the CP alone treated group compared to the control group. Co-administration of AM to the CP exposed rats significantly reduced the (P < 0.05) percentage of abnormal sperm as compared to the CP only group.
Conclusion: Overall, the present results represent the potential of AM to protect against CP induced reproductive toxicity.
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.
CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as pH-responsive system for controlled delivery of anticancer agents.