Publication: FORMULATION AND CHARACTERIZATION STUDIES OF DOXORUBICIN AND CYCLOSPORINE-A CO-ENCAPSULATION IN POLYMERIC NANOPARTICLES FOR ORAL CHEMOTHERAPY
| dc.contributor.author | SHAMALA NADARAJU | |
| dc.date.accessioned | 2023-10-06T15:25:11Z | |
| dc.date.available | 2023-10-06T15:25:11Z | |
| dc.date.issued | 2015 | |
| dc.description.abstract | Multidrug resistance (MDR) is a serious problem that causes failure in chemotherapy. P-glycoprotein (P-gp) is widely distributed in the intestine, liver and kidneys contributing as one of the major mechanism that causes efflux of chemotherapeutic agents, resulting in ineffective therapeutic level during treatment. However, recent advances in drug delivery systems have made it possible to circumvent MDR issues. In this study, an attempt was made to develop Poly-lactide co-glycolide (PLGA) nanoparticles for oral chemotherapy by co encapsulating doxorubicin (Dox) as the chemotherapeutic agent and cyclosporine-A (CysA) as the chemosensitizer that will function to inhibit P-gp to increase uptake of Dox. High Performance Liquid Chromatography (HPLC) methods were developed and validated for detection and quantification of Dox and CysA. Optimized Dox-CysA nanoparticles were reported to be in 214±4.56 nm of size, zeta potential of -30.1±9.42 and polydispersity index of 0.139±0.09.Transmission Electron Microscopy (TEM) image shows spherical nanoparticles. Differential Scanning Calorimetry (DSC) thermogram indicates Dox and CysA exist in amorphous form in PLGA nanoparticles. Dox and CysA nanoparticles were formulated separately alongside optimized nanoparticle for comparison purposes in drug release and cytotoxicity studies. Dox released slowest from Dox-CysA nanoparticles whilst CysA from CysA nanoparticles in Phosphate Buffer Saline (PBS), promising a controlled release. Cytotoxicity studies conducted on Caco 2 cell line, showed the lowest cell viability of 34%, for Dox-CysA loaded nanoparticles and 76.8% for Dox loaded nanoparticles while a combination of Dox loaded nanoparticles and CysA loaded nanoparticles at the same concentration gave a cell viability of 47.1%, with all treatment containing Dox at 0.71μg/ml. Co-administration of CysA together with Dox in the same nanoparticles formulation proves to increase the uptake of Dox in vitro. | en_US |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/32100 | |
| dc.language.iso | en | en_US |
| dc.publisher | International Medical University | en_US |
| dc.subject | Chemistry, Pharmaceutical | en_US |
| dc.subject | Drug Therapy | en_US |
| dc.subject | Drug Resistance, Multiple | en_US |
| dc.subject | Chromatography, High Pressure Liquid | en_US |
| dc.title | FORMULATION AND CHARACTERIZATION STUDIES OF DOXORUBICIN AND CYCLOSPORINE-A CO-ENCAPSULATION IN POLYMERIC NANOPARTICLES FOR ORAL CHEMOTHERAPY | en_US |
| dc.type | Thesis | |
| dspace.entity.type | Publication |