1. Academic Validation
  2. Elucidating a Potential Mechanism of Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate in Rats: Evidence of Lymphatic Absorption of Cyanocobalamin Using the Mesenteric Lymph Duct Cannulated Rat

Elucidating a Potential Mechanism of Permeability Enhancer Sodium N-[8-(2-hydroxybenzoyl) amino] caprylate in Rats: Evidence of Lymphatic Absorption of Cyanocobalamin Using the Mesenteric Lymph Duct Cannulated Rat

  • J Pharm Sci. 2022 Oct 10;S0022-3549(22)00454-3. doi: 10.1016/j.xphs.2022.10.003.
Po-Chang Chiang 1 Jia Liu 2 Karthik Nagapudi 2 Ricky Wu 2 Michael Dolton 3 Jacob Chen 4 Emile Plise 4 Liling Liu 4 Matthew R Durk 4
Affiliations

Affiliations

  • 1 Small Molecule Pharmaceutical Sciences, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: chiang.pochang@gene.com.
  • 2 Small Molecule Pharmaceutical Sciences, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
  • 3 Roche Products Pty Ltd, Millers Point NSW, Australia.
  • 4 Drug Metabolism and Pharmacokinetics, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
Abstract

Oral administration is the most popular and convenient route for drug delivery, yet the success of oral drug delivery is dependent on the ADME properties of the drug. Among those ADME properties, permeability is considered one of the key attributes for successful oral drug absorption. Hence, the utilization of permeability enhancers to improve drug oral absorption is an important area of research in drug delivery. A multitude of data suggests that sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) is an effective permeability enhancer. Despite its success, the mechanism of how SNAC works to enhance the oral absorption of compounds is poorly understood. To better understand how SNAC worked, we investigated the hypothesis of SNAC promotes lymphatic absorption of target compounds. In this study, cyanocobalamin was used as the model compound and mesenteric lymph duct cannulated rats were used to investigate its absorption with or without SNAC. The present study demonstrated that SNAC enhanced the lymphatic absorption of cyanocobalamin when the two were co-dosed in rats. Furthermore, levels of SNAC in lymph fluid and the systemic circulation were higher when co-dosed with cyanocobalamin.

Keywords

SNAC; lymph; oral absorption permeation enhancer; permeability; pharmacokinetics.

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