Evaluating the role of amino acids and isothermal dry particle coating in modulating buccal permeation of large molecule drug vancomycin

Abstract

The formulation and delivery of macromolecules through the oral route pose considerable challenges due to factors such as large molecular weight, pH sensitivity, and limited formulation approaches. This challenge is compounded if the drug is poorly permeable, necessitating innovative drug delivery strategies. Vancomycin, a widely prescribed glycopeptide antibiotic, has an oral bioavailability of less than 10%, leading to predominantly intravenous administration and potential patient discomfort. This study explores the potential of the buccal route as a non-invasive, highly vascularised alternative route of administration, offering a rapid onset of action while bypassing the first-pass metabolism. In this study, vancomycin was coated with L-glutamic acid using an isothermal dry particle coater to modulate permeation through the buccal cell line, TR146. Results confirm significant impact of both amino acid concentration and dry particle coating on the rate and extent of drug permeability. With the introduction of L-glutamic acid and utilisation of the isothermal dry particle coater, vancomycin's permeation profile increased six-fold compared to the control due to the formation of drug ion-pair complex. Imaging studies showed the presence of layered micronized glutamic acid particles on the surface of dry coated vancomycin particles which confirms the role of dry coating and amino acid concentration in modulating drug permeation. Microbiology experiments in Staphylococcus aureus, minimum inhibitory concentration and biofilm disruption studies, provided confirmatory evidence of antimicrobial activity of dry coated glutamic acid-vancomycin ion pair particulate structure. This study demonstrates, for the first-time, buccal delivery of dry coated large molecule drug, vancomycin, through controlled deposition of amino acid using innovative particle coating strategy.

Publication DOI: https://doi.org/10.1038/s41598-024-69144-6
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Aston University (General)
Funding Information: This work was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) Midlands Integrative Biosciences Training Partnership (MIBTP) case award in partnership with Aston Particle Technologies (APT) (BB/T00746X/1).
Additional Information: Copyright © The Author(s) 2024. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/
Uncontrolled Keywords: Amino acids,Biofilm,Biologics,Buccal delivery,Dry particle coating,Ion pair,Permeation,Vancomycin
Publication ISSN: 2045-2322
Data Access Statement: All data generated or analysed during this study are included in this published article.
Last Modified: 02 Dec 2024 09:08
Date Deposited: 16 Sep 2024 15:40
Full Text Link:
Related URLs: https://www.nat ... 598-024-69144-6 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2024-12
Published Online Date: 2024-08-24
Accepted Date: 2024-08-01
Authors: Rajabi, Anthony
Idrees, Muhammed
Rahman, Ayesha
Iyire, Affiong (ORCID Profile 0000-0002-2684-2260)
Wyatt, David
Koner, Jasdip
Mohammed, Afzal R. (ORCID Profile 0000-0002-5212-3040)

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