Intestinal permeability enhancement of benzopyran HP1-loaded nanoemulsions.


Federal University of Rio Grande do Sul, Postgraduate Program in Pharmaceutical Sciences, 2752 Ipiranga Avenue, Porto Alegre, Brazil. Electronic address: [Email]


The benzopyran HP1, a compound isolated from Hypericum polyanthemum, has demonstrated significant opioid-mediated antinociceptive activity after its oral administration. Despite the pharmacological potential, the poor aqueous solubility limits the oral absorption of this compound. For this reason, HP1 has been alternatively incorporated in lipid-based drug delivery systems. Given that nanoemulsions showed higher antinociceptive action than the free compound in a previous report, in this study, the main objective was to investigate the intestinal transport mechanisms of this system. The Ussing chamber model and rat jejunum were selected for this purpose. The apparent permeability coefficient of HP1 increased approximately 5.3 times after its incorporation in nanoemulsions. Considering that the absorptive transport of HP1 was significantly higher than the secretory transport, the participation of active transporters was suggested. The amount of HP1 in the acceptor chamber was reduced during permeability assays performed at 4 °C, supporting the hypothesis that active transporters are involved in the intestinal transport of this compound. The amount of free fatty acids released from nanoemulsion was approximately 60% after 90 min, demonstrating that part of this system is disassembled before absorption. Nanoemulsion constituents would be able to form new structures with biological constituents, leading to a rapid solubilization of HP1. A mucoadhesion rate of 50% was achieved by nanoemulsion after 30 min, which would also contribute to explain the higher absorption of this system. The particle size of the nanoemulsion is also compatible with endocytosis-mediated transport. Taken together, these results suggest that nanoemulsions containing HP1 could be efficiently delivered to humans considering that different absorption mechanisms are exploited.


Benzopyran HP1,Intestinal permeability,Nanoemulsion,Ussing chambers,