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Review Article

Piperine: A possible permeation enhancer for oral protein delivery

Indu Raghunath, Marina Koland, Anoop V. Narayanan.


Piperine, an alkaloid from black pepper (Piper nigrum), is a promising modulator that regulates the functional activities of various drug-metabolizing enzymes. It is postulated that it can improve the bioavailability of orally administered drugs by multiple mechanisms: modulates the membrane dynamics and permeability, inhibits P-glycoprotein Adenosine triphosphate (ATP)-dependent drug efflux pump) and gastric acid secretion, and increases gastrointestinal blood flow and absorption. Protein and peptide drugs are highly susceptible to enzymatic degradation and have poor permeation through intestinal epithelium because of high molecular weight and lack of lipophilicity. As a permeation enhancer, piperine can improve the absorption of orally administered peptide drugs by modulating the membrane fluidity and inhibiting the gut wall metabolizing enzymes, thereby enhancing their absorption and oral bioavailability. This review discusses the mechanisms involved in the absorption and metabolism of protein drugs and various barriers to these processes. It focuses on how piperine acts as a good permeation enhancer for orally administered drugs and how it could play a significant role in the absorption of macromolecular drugs. The supremacy of using a lipophilic molecule such as piperine to overcome the lipoidal barriers for macromolecular delivery is also discussed. Based on these mechanisms and concepts, this review aims to showcase the possibility of including a natural permeation enhancer such as piperine to improve the oral absorption of peptides.

Key words: Piperine, permeation enhancers, drug delivery, nanocarriers, oral bioavailability, macromolecules, P glycoprotein

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