International Journal of Nanomedicine (Jul 2021)
Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
Abstract
Santosh Bashyal,1 Jo-Eun Seo,1 Taekwang Keum,1,2 Gyubin Noh,1,2 Shrawani Lamichhane,1,2 Jeong Hwan Kim,1,2 Chang Hyun Kim,3 Young Wook Choi,3 Sangkil Lee1,2 1College of Pharmacy, Keimyung University, Daegu, Republic of Korea; 2Center for Forensic Pharmaceutical Science, Keimyung University, Daegu, Republic of Korea; 3College of Pharmacy, Chung-Ang University, Seoul, Republic of KoreaCorrespondence: Sangkil LeeCollege of Pharmacy, Keimyung University, 1095 Dalgubeol-Daero, Dalseo-Gu, Daegu, 42601, Republic of KoreaTel +82 53 580 6655Fax +82 53 580 5164Email [email protected]: The clinical use of therapeutic peptides has been limited because of their inefficient delivery approaches and, therefore, inadequate delivery to target sites. Buccal administration of therapeutic peptides offers patients a potential alternative to the current invasive routes of administration.Purpose: The aim of the study was to fabricate hydrophobic ion-pairing (HIP)-nanocomplexes (C1 and C2) utilizing anionic bile salts and cationic peptides, and to assess their permeability across TR146 buccal cell layers and porcine buccal tissue.Methods: C1 and C2-nanocomplexes were fabricated using the HIP approach. In addition, their physiochemical and morphological attributes, in vitro and ex vivo permeability properties, and qualitative and quantitative cellular uptake were evaluated and compared. The localization of C1 and C2-nanocomplexes in porcine buccal tissue was determined using confocal laser scanning microscopy.Results: The C1-nanocomplex was the superior nanocarrier and significantly enhanced the transport of insulin across TR146 cell layers and porcine buccal tissue, exhibiting a 3.00- and 51.76-fold increase in permeability coefficient, respectively, when compared with insulin solution (p C2 > insulin solution.Conclusion: In this study, we highlighted the efficacy of potential nanocarriers in addressing the daunting issues associated with the invasive administration of insulin and indicated a promising strategy for the buccal administration and delivery of this life-saving peptide hormone.Keywords: hydrophobic ion-pairing, bile salts, peptide delivery, buccal drug delivery, buccal absorption, TR146 cells, porcine buccal tissue
