IN VITRO ANTICANCER ACTIVITY OF 6–THIOGUANINE AND 6-THIOGUANINE LOADED CHITOSAN NANOPARTICLES WITH OR WITHOUT CURCUMIN AND PHARMACOKINETIC STUDIES IN RATS
| dc.contributor.advisor | RAVI KUMAR, P(MAJOR) | |
| dc.contributor.advisor | PRAKASH, N | |
| dc.contributor.advisor | SRINIVASA RAO, G | |
| dc.contributor.advisor | RAMA DEVI, V | |
| dc.contributor.advisor | MURALIDHAR, M | |
| dc.contributor.author | RASHMI, R | |
| dc.date.accessioned | 2020-06-05T05:45:43Z | |
| dc.date.available | 2020-06-05T05:45:43Z | |
| dc.date.issued | 2019-08 | |
| dc.description | THESES | en_US |
| dc.description.abstract | Cancer is the second leading cause of mortality in the world. Cancer nanotherapeutics are rapidly progressing and being implemented to overcome several limitations of conventional drug delivery systems. 6 thioguanine encapsulated chitosan nanoparticles ( 6 – TG – CNPs ) were formulated by ionic - gelation method. Morphologically , the 6 – TG - CNPs were spherical in shape and showed mean size, PDI, z eta potential and e ntrapment eff iciency of 261.63±6.01nm, 0.3 4 ±0.10, + 15.97±0.46mV and 44.27 per cent , respectively. IR spectra confirmed 6 - TG complex with chitosan. In vitro drug release profile of 6 - TG - CNPs revealed slow but increased ( 91.40 ± 1.08 per cent at 48h) release at pH 4.8 compared to less and sustained ( 73.96 ± 1.12 per cent at 48h) release at pH 7.4. MTT assay was conducted on MCF - 7 and PA - 1 cell lines at 48h incubation to determine per cent cell viability . IC 50 values of 6- TG, 6 - TG - CNPs and curcumin for MCF - 7 were 23.09, 17.82 and 15.73μM , respectively. Likewise, IC 50 values of 6 - TG, 6 - TG - CNPs and c urcumin for PA - 1 were 5.81, 3.92 and 12.89μM , respectively. Combination of 6-TG-CNPs (IC25) with curcumin (IC25) on PA-1 and MCF-7 showed percent cell viability of 43.67±0.02 and 49.77±0.05, respectively. The in vitro cytotoxicity potential in terms of per cent cell viability, early apoptosis, G2/M phase arrest and global DNA demethylating activity of 6-TG-CNPs alone and in combination with curcumin proved to be more effective than that of 6-TG on PA-1 cells. The Cmax of 6-TG in 6-TG-CNPs alone and 6-TG-CNPs in curcumin pre-treated groups was found to increased by 1.6-fold and 2-fold, respectively when compared to those observed with 6-TG treated group. The rate and extent of 6-TG absorption was increased by 2.5-fold following 6-TG-CNPs alone and 3.2-fold in curcumin followed by 6-TG-CNPs treated group compared to those observed with 6-TG treated group. The enhanced Cmax and AUC for 6-TG were in the order of curcumin pre-treatment + 6-TG-CNPs>6-TG-CNPs>6-TG groups. The apparent volume of distribution was substantially lower for 6-TG in 6-TG-CNPs alone and 6-TG-CNPs in curcumin pre-treated groups when compared to those observed with 6-TG treated group. Apart from this, volume of distribution at steady-state was also found lower for 6-TG in both the 6-TG-CNPs treated groups. These PK parameters suggests the better tumour targeting efficiency of 6-TG nanoformulations with less toxicity in off-target tissues. Thus, the 6-TG encapsulated chitosan nanoparticles prepared in the present study used either alone or in combination with curcumin present a wide scope for efficient delivery of 6-TG at the target sites. | en_US |
| dc.identifier.uri | http://krishikosh.egranth.ac.in/handle/1/5810147007 | |
| dc.keywords | RATS;ANTICANCER ACTIVITY;6-THIOGUANINE;CHITOSAN NANOPARTICLES;CURCUMIN;PHARMACOKINETIC STUDIES | en_US |
| dc.language.iso | en | en_US |
| dc.pages | 159 | en_US |
| dc.publisher | SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA | en_US |
| dc.sub | Veterinary Pharmacology | en_US |
| dc.theme | IN VITRO ANTICANCER ACTIVITY OF 6–THIOGUANINE AND 6-THIOGUANINE LOADED CHITOSAN NANOPARTICLES WITH OR WITHOUT CURCUMIN AND PHARMACOKINETIC STUDIES IN RATS | en_US |
| dc.these.type | Ph.D | en_US |
| dc.title | IN VITRO ANTICANCER ACTIVITY OF 6–THIOGUANINE AND 6-THIOGUANINE LOADED CHITOSAN NANOPARTICLES WITH OR WITHOUT CURCUMIN AND PHARMACOKINETIC STUDIES IN RATS | en_US |
| dc.type | Thesis | en_US |