PEGYLATED GEMCITABINE AND METHOTREXATE: IN VITRO CYTOTOXICITY ANALYSIS AND IN VIVO DRUG RELEASE PROFILING TO ASSESS THEIR ENHANCED BLOOD CIRCULATION

In the present study, four new pegylated drugs were synthesized to investigate the anticancer activity. All the compounds were characterized on the basis of FTIR and 1HNMR. The new compounds were evaluated against HCT116 cell line by CellTiter-Glo® 3D cell viability assay. The sustained release pattern of newly synthesized compounds were also evaluated, slow released lasts for 240 h which was confirmed by in vivo and in vitro drug release profile. The sustained and controlled release behavior of pegylated drugs over the extended period of time showed a linear profile and this release pattern was not limited to diffusion process instead supporting chemically controlled release pattern which was dependent only on how fast the compound hydrolyzed. The newly designed pegylated drugs showed almost same killing effect against the cancer cells as the free drugs. The compounds with lower cLogP value showed more antiproliferative (lower IC50) effect due their higher cell permeability.