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.
OBJECTIVES: Based on the multitargeted biological activities approach of ligustrazine based chalcones, in current study 18 synthetic ligustrazine-containing α, β-unsaturated carbonyl-based 1, 3-Diphenyl-2-propen-1-one derivatives were evaluated for their inhibitory effects on growth of five different types of cancer cells.
METHODS: All compounds were evaluated for anticancer effects on various cancer cell lines by propidium iodide fluorescence assay and various other assays were performed for mechanistic studies.
RESULTS: Majority of compounds exhibited strong inhibition of cancer cells especially synthetic compounds 4a and 4b bearing 1-Pyridin-3-yl-ethanone as a ketone moiety in main structural backbone were found most powerful inhibitors of cancer cell growth. Most active 9 compounds among whole series were selected for further studies related to different cancer targets including EGFR TK kinases, tubulin polymerization, KAF and BRAFV600E.
CONCLUSION: Synthetic derivatives including 4a-b and 5a-b showed multitarget approach and showed strong inhibitory effects on EGFR, FAK and BRAF while three compounds including 3e bearing methoxy substitution, 4a and 4b with 1- pyridin-3-yl-ethanone moiety showed the inhibition of tubulin polymerization.
MATERIALS AND METHODS: Overall, 180 samples were used for polymerization shrinkage (buoyancy and optical methods) and degree of conversion tests in which they were divided into Group 1, nanofilled composite (Filtek-Z350- XT; 3M ESPE, St Paul, MN 55144-1000, USA), Group 2, microhybrid composite (Zmack-Comp), and Group 3, nanohybrid composite (Zr-Hybrid). Polymerization shrinkage test was performed using buoyancy and optical methods. For buoyancy method, samples were weighed in air and water to calculate the shrinkage value, whereas, for optical method, images of nonpolymerized samples were captured under a digital microscope and recaptured again after light-cured to calculate the percentage of shrinkage. Degree of conversion was tested using Fourier-transform infrared spectroscopy spectrometer.
STATISTICAL ANALYSIS: Data were analyzed using one-way analysis of variance complemented by post hoc Dunnett's T3 test for polymerization shrinkage and Tukey's honestly significant difference test for degree of conversion. Level of significance was set at p < 0.05.
RESULTS: Group 3 demonstrated similar polymerization shrinkage with Group 1, but lower shrinkage (p < 0.05) than Group 2 based on buoyancy method. However, optical method (p < 0.05) showed that Group 3 had the lowest shrinkage, followed by Group 1 and lastly Group 2. Besides, Group 3 showed a significantly higher degree of conversion (p < 0.05) than Group 1 and comparable conversion value with Group 2.
CONCLUSIONS: Zirconia-reinforced rice husk nanohybrid composite showed excellent shrinkage and conversion values, hence can be considered as an alternative to commercially available composite resins.