d absorption of CPT11 preferentially in the stomach should boost its oral systemic bioavailability against tumor cells by escalating the proportion of SN-38 that reaches the tumor in active type. As a result, the oral MMP-9 Storage & Stability delivery of CPT11 applying a gastroretentive drug delivery system (DDS; GRDDS) to locally release CPT11 in an acidic condition of stomach will be helpful for the therapeutic efficacy. Moreover, the oral delivery of CPT11 applying a GRDDS would also stop CPT11 from transiting towards the reduced GI tract, whereby avoiding efflux by P-gp to lower its bioavailability. Lately, escalating accumulating evidence has demonstrated that non-cytotoxic naturally occurring dietary and herbal components are capable of interacting with each CYP3A metabolizing enzymes and P-gp transporters (Cho et al., 2011; Yang et al., 2015). Amongst them, MT2 Formulation silymarin, a flavonoid complex extracted from seeds on the milk thistle, is in a position to inhibit CYP3A4, UGT1A1, and ABC transporters (van Erp et al., 2005; Mirkov et al., 2007; Lin et al., 2008). Baicalein, the key flavonoid in Scutellariae radix, was reported to modulate the CYP3A subfamily and/or P-gp (Cho et al., 2011; Li et al., 2011). An in vitro study reported that glycyrrhizic acid (GA) inhibited the function of P-gp, in a comparable solution to glycyrrhetinic acid (GLA), a major metabolite of GA (Yoshida et al., 2006). In addition, it was also reported that GLA is an inhibitor of CYP3A, CYP1A1, and CYP2E1 in rat liver microsomes (Yang et al., 2001; Nabekura et al., 2008; Tu et al., 2010). Thus, all four prospective dual-function inhibitors for CYP 3A and P-gp had been chosen to examine their effects around the oral bioavailability of CPT11 within this study. Nevertheless, the poor water solubilities of CPT11 as well as the 4 dual-function inhibitors are nevertheless an awesome challenge for oral delivery achieving a preferred successful concentration for therapy. SMEDDSs are on the list of most successful nano-range DDSs, which incorporate pre-concentrates of oils, a surfactantDRUG DELIVERYmixture, a cosurfactant, and also a drug. On dilution with GI fluid, the preconcentrates self-microemulsify into nano-range oil droplets containing drug molecules (Pouton, 2000). SMEDDSs require high surfactant/cosurfactant concentrations to reduce the surface tension amongst the oil and water phases and obtain zero interfacial tension, hence top to improved toxicity (Lawrence Rees, 2000). From this viewpoint, lecithin-based SMEDDSs are specifically desirable considering that lecithin is usually a naturally occurring nontoxic biological surfactant (Yuan et al., 2008), as a type of phospholipid that functions as a vital element on the cell membrane to keep membrane fluidity and an absorption enhancer to facilitate drug absorption (Jin et al., 2013). Negi et al. (2013) reported that a SMEDDS formulation of CPT11 with excipients getting P-gp modulation activity resulted in drastically improved oral bioavailability (approximately 4-fold), indicating that it is a promising technique to orally deliver CPT11 in addition to a dual-function inhibitor by lecithin-based SMEDDSs by enhancing the oral bioavailability of CPT11 along with the formation and accumulation on the SN-38 active metabolite. The improvement of lecithin-based self-nanoemulsifying nanoemulsion preconcentrates (LBSNENPs) to load CPT-11 and 4 dual-function inhibitors for oral delivery of resultant self-nanoemulsifying nanoemulsions (LBSNENAs) with all the possible to improve the oral bioavailability was adopted from those previ