Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube:cytotoxicity, apoptosis and invivo roentgenography

BACKGROUND AND PURPOSE We aimed to develop a dosage form comprising of Capecitabine loaded carbon nanotubes for its targeted delivery to the colon. EXPERIMENTAL APPROACH Single walled carbon nanotubes (SWCNT) were functionalized by -COOH and chitosan along with folic acid. Capecitabine was loaded in these SWCNT’s and the system was analyzed by FTIR, SEM, Raman spectroscopy. Percent drug loading was assessed and the cytotoxicity (COLO320DM and HT29) was verified by using MTT and SRB assay. The apoptosis study was carried out by flowcytometry. The system was enclosed in enteric coated capsule with pH sensitive polymers and characterized for invitro disintegration, dissolution and invivo roentgenographic studies. KEY RESULTS FTIR, Raman and XRD studies indicated the confirmation of attachments, whereas SEM exhibited size range of 200-500 nm. Drug loading capacity was observed to be 94.63±1.07 %. Cytotoxicity studies of Capecitabine and FA–CHI-F-SWCNT-Capacitabine against COLO320DM by using MTT assay showed that FA–CHI-F-SWCNT-Capacitabine exhibited 86.45±0.5788% inhibition whereas pure Capecitabine showed 50.52±0.3106% inhibition. Against HT29, the % inhibition was observed to be 82.76±0.4668 % and 56.41±0.2316 % respectively for FA–CHI-F-SWCNT-Capacitabine and pure Capacitabine. In case of SRB assay of COLO320DM, the FA–CHI-F-SWCNT-Capacitabine exhibited 89.62±0.4095 % inhibition and Capecitabine showed 84.36±0.2559% inhibition, whereas against HT29, FA–CHI-F-SWCNT-Capacitabine showed 81.36±0.2958 % inhibition and Capacitabine exhibited 90.62±0.4196 % inhibition. CONCLUSION AND IMPLICATIONS FA-CHI-FSWCNT loaded system exhibited better cytotoxicity compared with pure drug, Invivo studies revealed that the prepared capsule formulation remains intact in the stomach thereby preventing drug release in the gastric milieu to achieve targeting in colon.