Engineering a Novel Mesoporous Silica-Lipid Hybrid Carrier for Oral Peptide Delivery

Abstract

The cornerstone of drug administration routes is oral delivery due to its convenience, non-invasiveness, and safety. Yet, utilising this route for peptide oral delivery is quite challenging due to the harsh environment and limited permeability of the gastrointestinal tract. Nonetheless, many researchers have worked extensively to enhance the oral delivery of peptides using numerous approaches, such as lipids, physical approaches, and mesoporous silica. Poor delivery and absorption through the intestinal epithelium constitute some of the key barriers. Hence, a novel carrier was formulated using mesoporous silica equipped with stearic acid needle-like structures on the surface, to enhance the peptide interaction with epithelial cells. This carrier was successfully constructed with microparticle silica after studying the factors that govern the peptide loading and the needles’ presence on the surface. Subsequently, this carrier was loaded with a model peptide (octreotide acetate), and its absorption profile studied using Caco-2 cells. Octreotide absorption from the carrier was higher than the unloaded peptide. In addition, using this carrier has presented levels of permeation similar to values of permeation enhancers, which could be attributed to stearic acid needles presence on the surface that enhanced cell interaction. The factors that affect protein loading into silica carriers were investigated by incorporating two proteins with different molecular weights into the carrier. The loading process was governed by diffusion, while loading efficiency seemed to be highly controlled by solvent’s viscosity, polarity, and protein size. Furthermore, utilising imaging techniques such as confocal microscopy proved valuable in identifying protein’s positioning after diffusion based on 3D imaging. Finally, the ability to compress silica into a dosage form was studied in addition to determining the release behaviour of protein from the carrier. Ultimately, compressing silica into tablets is achievable; however, this process is driven by the silica type, amount used, diluent composition, and compression force.

Publication DOI: https://doi.org/10.48780/publications.aston.ac.uk.00047172
Divisions: College of Health & Life Sciences > Aston Pharmacy School
Additional Information: Copyright © Mohamad Anas Al Tahan, 2023. Mohamad Anas Al Tahan asserts his moral right to be identified as the author of this thesis. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that its copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without appropriate permission or acknowledgement. If you have discovered material in Aston Publications Explorer which is unlawful e.g. breaches copyright, (either yours or that of a third party) or any other law, including but not limited to those relating to patent, trademark, confidentiality, data protection, obscenity, defamation, libel, then please read our Takedown Policy and contact the service immediately.
Institution: Aston University
Uncontrolled Keywords: Protein Oral Delivery,Mesoporous Silica,Absorption,Permeation Enhancers,Cell Culture,Protein Diffusion,Tablets
Last Modified: 23 Jan 2025 16:51
Date Deposited: 23 Jan 2025 16:49
Completed Date: 2023-12
Authors: Al Tahan, Mohamad Anas

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