Novel oleic acid derivatives enhance buccal permeation of didanosine

Abstract

The aim of this study was to explore the potential of novel oleic acid (OA) derivatives as buccal permeation enhancers for the delivery of didanosine (ddI). The OA derivatives, i.e. ester derivative (OA1E), the dicarboxylic acid derivative (OA1A) and the bicephalous dianionic surfactant (OA1ANa) were synthesized and their effects were compared to the parent OA. OA, OA1E, OA1A and OA1ANa at 1% w/w all showed potential for enhancing the buccal permeability of ddI with enhancement ratio (ER) of 1.29, 1.33, 1.01 and 1.72, respectively. OA1ANa at 1% w/w demonstrated the highest flux (80.30 ± 10.37 µg cm⁻²h), permeability coefficient (4.01 ± 0.57 × 10⁻³ cm h⁻¹) and ER (1.72). The highest flux for ddI (144.00 ± 53.54 µg cm⁻²h) was reported with OA1ANa 2% w/w, which displayed an ER of 3.09 more than that with ddI alone. At equivalent concentrations, OA1ANa (ER = 3.09) had a significantly higher permeation-enhancing effect than its parent OA (ER = 1.54). Histomorphological studies confirmed that OA1ANa at all concentrations (0.5, 2.0 and 6.0% w/w) had no adverse effects on the mucosae. Morphological changes such as vacuoles formation and increased intercellular spaces were attributed to the buccal permeation-enhancing effect of OA1ANa. This study demonstrated the potential of novel OA derivatives as buccal permeation enhancers. OA1ANa at 2% w/w was also identified as the optimal novel OA derivative to widen the pool of fatty acid derivatives as chemical permeation enhancers for buccal drug delivery.

• Antiretroviral
• buccal
• didanosine
• oleic acid derivatives
• permeation enhancers

Acknowledgements

The authors are grateful to University of KwaZulu-Natal (UKZN), Medical Research Council of South Africa and National Research Foundation of South Africa for the financial support of this study. We acknowledge staff of The BRU (UKZN), Dr. Sanil Singh, Dr. Linda Bester and Ms. Ritta Radebe for assisting with sourcing the pigs for buccal mucosa. The authors sincerely acknowledge staff of Electron Microscope Unit (UKZN), Dr. Nelisha Murugan, Mr. Phillip Christopher and Mr. Vishal for technical assistance with LM and TEM microphotographs. Dr. Chunderika Mocktar, Mr. Leslie Murugan and Ms. Melissa Ramtahal are also appreciated for general technical assistance in the laboratory.