ABSTRACT
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.
Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Bentonite/chemistry , Drug Carriers/chemistry , Polyesters/chemistry , Animals , Antineoplastic Agents/pharmacokinetics , Bentonite/administration & dosage , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Cells, Cultured , DNA Damage/drug effects , Delayed-Action Preparations , Drug Carriers/administration & dosage , Female , HeLa Cells , Humans , Lymphocytes/drug effects , Polyesters/administration & dosage , Rats , Rats, Wistar , Sodium/chemistry , Tamoxifen/administration & dosage , Tamoxifen/chemistry , Tamoxifen/pharmacokinetics , X-Ray Diffraction/methodsABSTRACT
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.
