Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

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, R...

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Autores principales:	Bashyal S, Seo JE, Keum T, Noh G, Lamichhane S, Kim JH, Kim CH, Choi YW, Lee S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hydrophobic ion-pairing bile salts peptide delivery buccal drug delivery buccal absorption tr146 cells porcine buccal tissue Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bbbd43bafaa4455395fb3c2f76475982
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spelling	oai:doaj.org-article:bbbd43bafaa4455395fb3c2f764759822021-12-02T15:05:55ZFacilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation1178-2013https://doaj.org/article/bbbd43bafaa4455395fb3c2f764759822021-07-01T00:00:00Zhttps://www.dovepress.com/facilitated-buccal-insulin-delivery-via-hydrophobic-ion-pairing-approa-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Santosh 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 skdavid@kmu.ac.krBackground: 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 < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18- and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > 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 tissueBashyal SSeo JEKeum TNoh GLamichhane SKim JHKim CHChoi YWLee SDove Medical Pressarticlehydrophobic ion-pairingbile saltspeptide deliverybuccal drug deliverybuccal absorptiontr146 cellsporcine buccal tissueMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 4677-4691 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydrophobic ion-pairing bile salts peptide delivery buccal drug delivery buccal absorption tr146 cells porcine buccal tissue Medicine (General) R5-920
spellingShingle	hydrophobic ion-pairing bile salts peptide delivery buccal drug delivery buccal absorption tr146 cells porcine buccal tissue Medicine (General) R5-920 Bashyal S Seo JE Keum T Noh G Lamichhane S Kim JH Kim CH Choi YW Lee S Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
description	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 skdavid@kmu.ac.krBackground: 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 < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18- and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > 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
format	article
author	Bashyal S Seo JE Keum T Noh G Lamichhane S Kim JH Kim CH Choi YW Lee S
author_facet	Bashyal S Seo JE Keum T Noh G Lamichhane S Kim JH Kim CH Choi YW Lee S
author_sort	Bashyal S
title	Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
title_short	Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
title_full	Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
title_fullStr	Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
title_full_unstemmed	Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation
title_sort	facilitated buccal insulin delivery via hydrophobic ion-pairing approach: in vitro and ex vivo evaluation
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/bbbd43bafaa4455395fb3c2f76475982
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Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

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