Enhancing the oral bioavailability of fisetin: polysaccharide-based self nano-emulsifying spheroids for colon-targeted delivery

Fisetin (FS) is a flavonoid that possesses antioxidant andanti-inflammatory properties against ulcerative colitis. FS shows poor dissolutionrate and permeability. An attempt has been made to develop colon-targeted solidself-nanoemulsifying drug delivery systems (S-SNEDDS) of FS. Initially, liquid (L)SNEDDS were prepared by loading FS into isotropic mixture of L-SNEDDS was preparedusing Labrafil M 1944 CS, Transcutol P, and Tween 80. These L-SNEDDS were furtherconverted into solid (S) SNEDDS by mixing the isotropic mixture with 1:1:1 ratio ofguar gum (GG), xanthan gum (XG) and pectin (PC) [GG:XG:PC (1:1:1)]. Aerosil-200(A-200) was added to enhance their flow characteristics. Further, they wereconverted into spheroids by extrusion-spheronization technique. The solid-statecharacterization of S-SNEDDS was done by SEM, DSC, and PXRD, which revealed that thecrystalline form of FS was converted into the amorphous form. In the dissolutionstudy, S-SNEDDS spheroids [GG:XG:PC (1:1:1)] exhibited less than 20% drug releasewithin the first 5 h, followed by rapid release of the drug between the 5th and 10thh, indicating its release at colonic site. The site-specific delivery of FS to colonvia FS-S-SNEDDS spheroids was confirmed by conducting pharmacokinetic studies onrats. Wherein, results showed delay in absorption of FS loaded in spheroids up to 5h and achievement of Cmax at 7h, whereas L-SNEDDS showed rapid absorption of FS.Furthermore, FS-L-SNEDDS and FS-S-SNEDDS spheroids [GG:XG:PC (1:1:1)] increased oralbioavailability of FS by 6.86-fold and 4.44-fold, respectively, as compared tounprocessed FS. Graphical Abstract: (Figure presented.)