Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances

Abhijit A Date; Neha Desai; Rahul Dixit; Mangal Nagarsenker

Disclosures

Nanomedicine. 2010;5(10) 

In This Article

SNEDDS: Potential Explored

The ability of SNEDDS to improve oral delivery of several therapeutic agents (belonging to various therapeutic classes) has been established by various in vitro and/or in vivo methodologies. The potential mechanisms responsible for improvement in oral bioavailability by SNEDDS are shown in Figure 4. Most of the investigations described so far have evaluated the pharmacokinetics of the drug when incorporated in SNEDDS and very few investigations have demonstrated pharmacodynamic efficacy. Although pharmacokinetic studies are sufficient to establish proof of concept for SNEDDS, the results of the pharmacokinetic study should preferably be corroborated by pharmacodynamic studies. This is particularly important for drugs such as simvastatin, atorvastatin and ezetimibe, which do not show pharmacokinetic–pharmacodynamic correlation. Hence, although potential of nanoemulsions/SNEDDS in improving oral bioavailability of atorvastatin and ezetimibe has been established,[13,88] the increase in the drug bioavailability need not translate into increases in the pharmacodynamic effects of these drugs.[89] Such aspects should be carefully considered while planning investigations on the SNEDDS. The key investigations that describe the potential of SNEDDS in oral drug delivery are listed in Table 4 and some of them have been discussed below.[12,48,50,54,63–65,67,68,71,87,90–98]

Figure 4.

Potential mechanisms of improvement of oral bioavailability by self-nanoemulsifying drug delivery systems.
SNEDDS: Self-nanoemulsifying drug delivery systems.

Improving Oral Delivery of Proteins

Oral delivery of peptides is a very challenging task owing to their extreme hydrophilicity, poor permeability and poor stability in the GI environment. Several strategies are being explored for improving oral absorption of proteins. Recently, Shao and coworkers evaluated the ability of SNEDDS to improve oral bioavailability of β-lactamase, a model protein.[90–92] In order to improve the loading of the hydrophilic protein in the SNEDDS, investigators adsorbed the protein on the hydrogenated phospholipids. The phospholipid-adsorbed protein was incorporated into SNEDDS, and the potential of SNEDDS to improve Caco-2 cell permeability and oral bioavailability was evaluated. Interestingly, peptide-loaded SNEDDS could significantly improve the permeability and oral bioavailability of the β-lactamase. However, investigators also observed that the bioavailability of the protein-loaded SNEDDS when coadministered with the phosphate buffered saline was considerably lower than that of protein-loaded SNEDDS diluted with water (and administered as is). This clearly indicates the influence of the electrolyte content on the in vivo performance of the SNEDDS. Hence, evaluating electrolyte tolerance of SNEDDS before finalizing the formulation for in vivo studies is a critical step in SNEDDS design. Another problem observed was leakage of the protein from SNEDDS after dilution with aqueous phase. This problem can be anticipated as protein was adsorbed on the phospholipids and was not inside the phospholipid core. It could be possible to solve this problem using an appropriate ion pair for the protein, which would increase the lipophilicity of the protein and reduce leakage. Alternatively, protein can be conjugated to phospholipids or any other suitable lipids, as evidenced by Ruan and coworkers.[93]

Improving Oral Delivery of Natural Phytochemicals

Natural phytochemicals are drawing great attention from clinicians owing to their multitude of actions. Natural phytochemicals have demonstrated potential in the prevention and/or treatment of various diseases, such as cancer, arthritis, diabetes and hepatitis. The majority of phytochemicals suffer from problems such as poor water solubility and poor metabolic stability, which limit their use in the clinic. As mentioned previously, SNEDDS can be an attractive approach for drugs with poor water solubility and/or poor metabolic stability. Researchers have established that SNEDDS can significantly improve the oral bioavailability/therapeutic efficacy of several natural phytochemicals belonging to diverse classes, such as natural antioxidants,[50,71] triterpenoids,[73] essential oils,[95] alkaloids,[93] carotenoids[64] and hepatoprotective agents.[96]

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