Shiva Shankaran Chettiar

Biodegradable gelatin–ciprofloxacin–montmorillonite composite hydrogels for controlled drug release and wound dressing application

This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.

Evaluation of clay/poly (l-lactide) microcomposites as anticancer drug, 6-mercaptopurine reservoir through in vitro cytotoxicity, oxidative stress markers and in vivo pharmacokinetics

Intercalation of 6-mercaptopurine (6-MP), an antineoplastic drug in interlayer gallery of Na(+)-clay (MMT) was further entrapped in poly (L-lactide) matrix to form microcomposite spheres (MPs) in order to reduce the cell toxicity and enhance in vitro release and pharmacokinetic proficiency. The drug-clay hybrid was fabricated via intercalation by ion-exchange method to form MPs from hybrid. In vitro drug release showed controlled pattern, fitted to kinetic models suggested controlled exchange and partial diffusion through swollen matrix of clay inter layered gallery. The in vitro efficacy of formulated composites drug was tested in Human neuroblastoma cell line (IMR32) by various cell cytotoxic and oxidative stress marker indices. In vivo pharmacokinetics suggested that the intensity of formulated drug level in plasma was within remedial borders as compared to free drug. These clay based composites therefore have great potential of becoming a new dosage form of 6-MP.

Cytogenetic Alteration Induced by Nickel and Chromium in Human Blood Cultures and its Amelioration by Curcumin

Abstract Tanners, welders and workers in various industries are exposed to acute and chronic toxicity of these heavy metals world wide. The present work is undertaken to evaluate the genotoxic effects of Ni and Cr at two different exposure intervals with a single dose and the amelioration of this toxicity using curcumin. Ni in form of nickel chloride (4.216 X 10-5M) and Cr as potassium dichromate (1.36 X 10-6M) were exposed for 24 and 69 hours to human blood lymphocyte cultures. The genotoxicity was measured by changes in acrocentric and telomeric association and C-anaphase. Results revealed a significant positive correlation between DNA damage and exposure time in Ni and Cr added cultures alone. Likewise it was also observed in cultures with combination of both prooxidants. Groups supplemented with curcumin (3.87 X 10-7M) showed insignificant cytogenetic damage indicating its protective role which was calculated as percentage amelioration. Thus these data proved curcumin as a protective agent against Ni and Cr induced genotoxicity.

Ameliorative effects of curcumin against lead induced toxicity in human peripheral blood lymphocytes culture

Abstract Lead, a heavy metal and multifaceted toxicant, is well studied for its distribution and toxicity in ecosystem, yet there is no consensus on its amelioration by any synthetic or phytochemical compounds. Curcumin, a known antioxidant and dietary element, is a well-known herb, for its therapeutic uses and having a wide spectrum of its beneficial properties against several adverse effects. Hence, the current study was taken into consideration to evaluate the ameliorative effects of curcumin (3.87 μM, i.e. 1.43 μg/ml) against lead acetate (doses: 10−6 M, i.e. 0.379 μg/ml and 10−4 M, i.e. 37.9 μg/ml, durations: 24 h and 69 h) induced genotoxicity and oxidative stress in human peripheral blood lymphocyte cultures (PBLC). On one hand, antigenotoxic and antioxidative potentials of curcumin against lead were simultaneously evaluated by the array of genotoxicity and oxidative stress indices. The result postulated that lead acetate showed dose- and duration-dependent increase in both genotoxicity and oxidative stress whereas curcumin, when added along with lead acetate, showed the significant amelioration in all genotoxic and oxidative stress-related indices. The study indicated that, due to alteration in antioxidant defense system, there is an adverse genotoxic effect of lead. On the other hand, curcumin, a potent antidote, can protect chromatin material against lead -mediated genotoxicity by balancing the activity of antioxidant defense system.