Enhanced antitumor efficacy of bile acid-lipid complex-anchored docetaxel nanoemulsion via oral metronomic scheduling

Enhancement of the anticancer effect of atorvastatin-loaded nanoemulsions by improving oral absorption via multivalent intestinal transporter-targeting lipids

“…In our previous study, we improved the oral absorption of poorly permeable drugs by ionic complex formation with a positively charged bile acid derivative via ASBT-mediated transport (Deng & Bae, 2020 ; Li et al., 2020 ; Pangeni et al., 2020 ; Subedi et al., 2022 ). Additionally, we constructed docetaxel- and etoposide-loaded nanoemulsive systems to increase aqueous solubility and intestinal permeability by physically anchoring deoxycholic acid (DOCA) in an ionic complex with the cationic lipid, 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP); we confirmed 249% and 1752% greater oral bioavailabilities, respectively, compared to the free drugs via ASBT-mediated endocytosis (Jha et al., 2020a ; Jha et al., 2020b )…”

“…In addition to the improvement of aqueous solubility, the further enhancement of cytotoxicity by ATV-NEs compared with ATV in 0.5% DMSO can be explained by enhanced cellular uptake along with the inhibition of multidrug resistance proteins (e.g. breast cancer receptor protein) expressed in MCF-7 and 4T1 cells by TPGS incorporated into the NEs (Jha et al., 2020a ).…”

“…To obtain stable ATV-loaded NEs (ATV-NEs), 10 mg of ATV were dispersed in 42 mg of oil (Capryol 90). Subsequently, 550 mg of a mixture of surfactant and co-surfactant (S mix ; Tween 80:Transcutol HP, 1:2 [w/w]), and 50 mg TPGS were added to form a self-microemulsifying drug delivery system (Ishak & Osman, 2015 ; Jha et al., 2020a ). Furthermore, to examine the improvement in permeability of ATV via ASBT- and SMVT-mediated transport, DOTAP was integrated with DOCA at a molar ratio of 1:1 by ionic complexation to form DOCA-TAP, as described previously (Jha et al., 2020a ).…”

“…Subsequently, 550 mg of a mixture of surfactant and co-surfactant (S mix ; Tween 80:Transcutol HP, 1:2 [w/w]), and 50 mg TPGS were added to form a self-microemulsifying drug delivery system (Ishak & Osman, 2015 ; Jha et al., 2020a ). Furthermore, to examine the improvement in permeability of ATV via ASBT- and SMVT-mediated transport, DOTAP was integrated with DOCA at a molar ratio of 1:1 by ionic complexation to form DOCA-TAP, as described previously (Jha et al., 2020a ). Then, effective enhancers, such as DOCA-TAP and/or Biotinyl PE, were anchored onto the S mix layer of ATV-NEs using a low-energy spontaneous emulsification method.…”

Physiology and Physical Chemistry of Bile Acids

“…BA-drug conjugates have been synthesized to make the drug target liver and to enhance its intestinal absorption, by exploiting the ability of the conjugate to enter the enterohepatic circulation exploiting the BA transport system. Based on these principles, BA-based nanocarriers and BADs have been synthesized to target the apical sodium-dependent BA transporter with inhibitors [107], antiviral [108] and anticancer [109] drugs. Moreover, drugs against hepatitis C virus and anticancer cytostatic drugs have been specifically targeted to the liver upon conjugation with BAs [110,111].…”