Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

Embryo-Protective Effects of Cerium Oxide Nanoparticles against Gestational Diabetes in Mice.

Gestational diabetes is defined as carbohydrate intolerance with onset or first recognition during pregnancy. Diabetes during pregnancy increases the incidences of congenital anomalies, in a mother and her embryo. Oxidative stress has been implicated to be responsible in diabetic embryopathy. In this study, we used nanoceria as an antioxidant for amelioration of diabetic embryopathy in diabetic mice. The female mice were divided into 5 groups (6 mice per group). Diabetes was induced by a single dose of streptozotocin (60 mg/kg IP) that dissolved in citrate buffer (pH = 4.6). Blood glucose was checked in 0,5,10, and 15 days of pregnancy. The diabetic state was confirmed when the blood glucose concentration exceeded 200 mg/dL. On the day 16 of pregnancy, all animals were anesthetized with ether and embryos were excised; then oxidative stress, pathological parameters, number of implantations, miscarriage, and live embryo were assayed. Histological study showed that diabetes induced abortion; decrease in weight of mothers, embryo, and the number of embryos were observed. In diabetic mice, significant increase in lipid peroxidation (LPO), ROS formation, and protein carbonyl content were observed. Glutathione (GSH) concentration is found to be decreased in embryo tissue in diabetic mice. Nanoceria treatment significantly inhibited embryonic oxidative stress and also pathologic changes in diabetic mice. Our research showed that diabetes act as a teratogen agent for fetal development and nanoceria abrogated diabetes induced embryopathy via its antioxidant effects. So, early detection of diabetes in pregnancy and antioxidant administration can attenuate these complications.