**3. Lipid nanocarriers and recent advancements in oral drug delivery**

Lipid‐based nanoformulations as drug delivery vehicles signify a promising strategy that incorporates or encapsulates the drug molecules and are biodegradable or biocompatible. They are containing nanosized droplets typically ranging from 0 to 250 nm [20]. The entrapped drug molecules can be taken intact and protected against degradation by gastrointestinal (GI) fluids, while drug absorption through the GI epithelium or lymphatic transport can be enhanced. Possible mechanisms of transport of these nanocarriers across GI mucosa are introduced later in the chapter. These focus on effects of size and surface properties of the nanocarriers on the nonspecific or targeted uptake by enterocytes and/or M cells. Applications of various oral nanocarrier formulations, such as lipid nanoparticles and SMEDDS/SNEDDS, are reviewed in several recent publications [4, 21, 22]. **Figure 1** shows an encapsulated SNEDDS designed for oral administration, which are the most efficient formulations for improving the apparent aqueous solubility of PWSDs.

Within the scope of the current chapter, the most advanced SNEDDS and/or SMEDDS systems have been explored as potential nanocarriers, which are much more stable kinetically and thermodynamically and showed great potential for improving the bioavailability of orally administered drugs. In a pure drug nanoparticle formulation, submicron size particles of drugs are stabilized in aqueous medium with generally regarded as safe (GRAS) listed excipients blend. Such formulation can be used for drugs with poor solubility in water and oil, high melting point, high log *P* and high dose.

When saquinavir (HIV protease inhibitor) in 1995 was marketed for the first time as mesylate salt formulation in a hard gelatin capsule (Invirase®), its bioavailability was only 4% and highly variable [23]. Later on, after 2 years, a self‐nanoemulsifying formulation of saquinavir (Forto‐ vase®) containing medium‐chain mono‐ and diglycerides, povidone and α‐tocopherol was able to increase bioavailability threefold higher than Invirase® in humans [23, 24]. Several other published [10, 25, 26] and unpublished case studies are also available that established the significance of rational approach in designing SMEDDS/SNEDDS which can improve the *in vivo* absorption of the PWSDs. The commercial product such as amprenavir (agenerase), ciprofloxacin (cipro), fenofibrate (fenogal), liponavir/ritonavir (kaletra, norvir), etc., have been formulated using suitable SMEDDS/SNEDDS [24, 27].

**Figure 1.** The encapsulated SNEDDS designed for oral administration of PWSDs. \*Adapted with permission from Ref. [21].
