Self-Healing Chitosan Hydrogels: Preparation and Rheological Characterization

The paper aims at the preparation of chitosan self-healing hydrogels, designed as carriers for local drug delivery by parenteral administration. To this aim, 30 hydrogels were prepared using chitosan and pyridoxal 5-phosphate (P5P), the active form of vitamin B6 as precursors, by varying the ratio of glucosamine units and aldehyde on the one hand and the water content on the other hand. The driving forces of hydrogelation were investigated by nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction, and polarized light microscopy (POM) measurements. NMR technique was also used to investigate the stability of hydrogels over time, and their morphological particularities were assessed by scanning electron microscopy (SEM). Degradability of the hydrogels was studied in media of four different pH, and preliminary self-healing ability was visually established by injection through a syringe needle. In-depth rheological investigation was conducted in order to monitor the storage and loss moduli, linear viscoelastic regime, and structural recovery capacity. It was concluded that chitosan crosslinking with pyridoxal 5-phosphate is a suitable route to reach self-healing hydrogels with a good balance of mechanical properties/structural recovery, good stability over time, and degradability controlled by pH

Cytotoxic substituted indolizines as new colchicine site tubulin polymerisation inhibitors

A potential microtubule destabilising series of new indolizine derivatives was synthesised and tested for their anticancer activity against a panel of 60 human cancer cell lines. Compounds 11a, 11b, 15a, and 15j showed a broad spectrum of growth inhibitory activity against cancer cell lines representing leukaemia, melanoma and cancer of lung, colon, central nervous system, ovary, kidney, breast, and prostate. Among them, compound 11a was distinguishable by its excellent cytostatic activity, showing GI50 values in the range of 10–100 nM on 43 cell lines. The less potent compounds 15a and 15j in terms of GI50 values showed a high cytotoxic effect against tested colon cancer, CNS cancer, renal cancer and melanoma cell lines and only on few cell lines from other types of cancer. In vitro assaying revealed tubulin polymerisation inhibition by all active compounds. Molecular docking showed good complementarity of active compounds with the colchicine binding site of tubulin