**5. Critical influencing factors**

It is claimed that the type of lipid (chain lengths and saturation degree) is one of the most essential factors that affect CM transport. Lipophilicity of short, medium and long-chain fatty acids and CM binding capacity both are significantly correlated with chain length. Reports say that transport via the portal vein there is preferred short-chain fatty acid, whereas medium-chain or long-chain fatty acids are prone to be transported via the lymph. Self-nanoemulsifying drug delivery systems (SNEDSS) composed of long-chain fatty acids than medium chain-fatty acids in lymph add proof to support the dependency of chain length [64]. Halofantrine, a particularly lipophilic drug, was used in a research of lipid-based vehicles to demonstrate that the lymphatic affinity of the vehicles followed the order of C18 (15.8%) > C8–10 (5.5%) > C4 (2.22%) > C0 (0.34%) [65]. An increase in FA chain length is highly correlated with

#### *Lipid as a Vehicle/Carrier for Oral Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.109672*

enhanced drug transport efficiency. This may be explained by higher affinity to intracellular CMs and lipoproteins by higher lipophilicity of long-chain fatty acid. Administered in oil solution of 1,3-dioctanoyl-2-linoleyl-*sn*-glycerol, abbreviation MLM to denote the position of "medium long medium" chains, enhances absorption of halofantrine while maintaining levels of lymphatic transport that are comparable to the level of sunflower oil solution. However, halofantrine formulation was made into SNEDSS which based on MLM and 1,3-dilinoyl-2-octanoyl-*sn*-glycerol, enclosed as LML to indicate "long-chain-long" chain lengths, lymphatic transport was found to be 17.9% and 27.4%, although the availability of plasma was 56.9% (MLM) and 37.2% (LML), respectively [66]. It is indicated that consideration of ratio and length of chain may be a way to change how drugs are distributed throughout various pathways.

Another factor is food effect that may enhance lymphatic transport and with bioavailability of plasma. Radio-labeled cannabinoid receptor agonist CRA13 have 72–75% oral bioavailability in fed dogs vs. 8–20% in fasted ones, with 43.7% through lymphatic transport [67]. After the meal has been taken total amount of halofantrine increases from 1.3% to 54% in lymphatic transport of the administered dose. Sometimes, consumption of food may slow down the process of absorption, but not necessarily affect systemic bioavailability and AUC. Regarding the food effect, there are some exceptions which should be noted. For example, after administration of high-fat food, the AUC of DDT with high CM binding efficiency enhances by 1.5-fold, however, under identical circumstances, diazepam with low CM binding efficiency shows no significant difference, lymphatic transport is higher for DDT but not for diazepam. Stimulation of CMs may have partly affected by the food effect. Intake of not only fat but high contents of carbohydrates also affects the higher production of CM [68]. Additionally, the bile salts produced during lipid digestion help to stabilize the mixed micelles that entrap the drug molecule. This is turn help to increase the drug absorption and CM formation inside the cell enterocytes. The importance of many endogenous bile salts is demonstrated by the drastically reduced halofantrine synthesis in lymph in bile duct salt-cannulated rats.
