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.

Montmorillonite/poly-(ε-caprolactone) composites as versatile layered material: reservoirs for anticancer drug and controlled release property.

This work evaluates intercalation of tamoxifen (Tmx) in interlayer gallery of Na(+)-MMT (Montmorillonite, MMT) (Tmx-MMT), which is further compounded with poly-(ε-caprolactone) (PCL) (Tmx-MMT/PCL, MPs), for oral chemotherapy of breast cancer. The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the intercalation of Tmx into the MMT interlayer that stabilized in the longitudinal monolayer mode by electrostatic interaction. No significant change in structural and functional properties of Tmx was found in the MMT layers. In vitro study of drug release profiles showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated moderate reduction in DNA damage when pristine Tmx was intercalated with MMT and formulated in composites. The Tmx-MMT hybrid efficacy was also confirmed on HeLa and A549 cancer cells by in vitro cell viability assay. In vivo pharmacokinetics (PK) of formulated Tmx in rats was examined and the results showed that plasma Tmx levels were within therapeutic window as compared to pristine Tmx. Therefore, Tmx-MMT hybrid and microcomposite particles (MPs) can be of considerable value in chemotherapy of malignant neoplastic disease with reduced side effects. This study clearly indicated that MMT not only plays a role as a delivery matrix for drug, but also facilitates significant increase in the delivery proficiency.

Layered inorganic nanocomposites: a promising carrier for 5-fluorouracil (5-FU).

We report here the intercalation of 5-fluorouracil (5-FU), an anticancer drug in interlayer gallery of Na(+) clay (Montmorillonite, MMT), with the assistance of biopolymer (chitosan, CS). The X-ray diffraction patterns, thermal and spectroscopic analyses indicated the drug intercalation into the clay interlayer space in support of CS and stabilized in the longitudinal monolayer by electrostatic interaction. In vitro drug release showed controlled release pattern. The genotoxic effect of drug was in vitro evaluated in human lymphocyte cell culture by comet assay, and results indicated significant reduction in DNA damage when drug was intercalated with clay and formulated in composites. The results of in vitro cell viability assay in cancer cells pointed at decreased toxicity of drug when encapsulated in Na(+)-clay plates than the pristine drug. In vivo pharmacokinetics, biodistribution, hepatotoxicity markers, e.g., SGPT and SGOT, and liver/testicular histology in rats showed plasma/tissue drug levels were within therapeutic window as compared to pristine drug. Therefore, drug-clay hybrid and composites can be of considerable value in chemotherapy of cancer with reduced side effects.

Influence of chirality of V(V) Schiff base complexes on DNA, BSA binding and cleavage activity.

New chiral V(V) Schiff base complexes (S)-[VO(OMe)L] and (R)-[VO(OMe)L] were synthesized and characterized by microanalysis, infrared (IR), UV-Visible, Circular dichroism (CD) spectroscopy and single crystal X-ray studies. The interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin (BSA) protein showed chiral expression DNA/protein binding strength. The influence of chirality was also observed in cytotoxicity assay of Hep 2 cells. (R)-[VO(OMe)L] enantiomer exhibited higher binding constant (5 ± 1 × 10(5) M(-1)) as compared to (S)-[VO(OMe)L] (8 ± 1 × 10(4) M(-1)). The fluorescence quenching, thermal melting and viscosity data suggest DNA surface and/or groove binding nature of the complexes and electrophoresis studies also showed greater activity for (R)-[VO(OMe)L] in cleaving DNA and protein as against (S)-[VO(OMe)L].