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Open AccessArticle

Rationally Designed Dendritic Silica Nanoparticles for Oral Delivery of Exenatide

1
School of Pharmacy, The University of Queensland, Brisbane QLD 4072, Australia
2
Mater Research Institute—The University of Queensland, Translational Research Institute, Woolloongabba QLD 4102, Australia
3
Center for Advanced Imaging, The University of Queensland, Brisbane QLD 4072, Australia
4
Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
5
Instituto de Engenharia Biomédica (INEB), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
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CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal
7
Australian Infectious Disease Research Centre—The University of Queensland Building 76 Room 155 Cooper Road, St. Lucia QLD 4067, Australia
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(8), 418; https://doi.org/10.3390/pharmaceutics11080418
Received: 9 July 2019 / Revised: 4 August 2019 / Accepted: 15 August 2019 / Published: 19 August 2019
(This article belongs to the Special Issue Porous Micro and Nanoparticles for Drug Delivery)
Type 2 diabetes makes up approximately 85% of all diabetic cases and it is linked to approximately one-third of all hospitalisations. Newer therapies with long-acting biologics such as glucagon-like peptide-1 (GLP-1) analogues have been promising in managing the disease, but they cannot reverse the pathology of the disease. Additionally, their parenteral administration is often associated with high healthcare costs, risk of infections, and poor patient adherence associated with phobia of needles. Oral delivery of these compounds would significantly improve patient compliance; however, poor enzymatic stability and low permeability across the gastrointestinal tract makes this task challenging. In the present work, large pore dendritic silica nanoparticles (DSNPs) with a pore size of ~10 nm were prepared, functionalized, and optimized in order to achieve high peptide loading and improve intestinal permeation of exenatide, a GLP-1 analogue. Compared to the loading capacity of the most popular, Mobil Composition of Matter No. 41 (MCM-41) with small pores, DSNPs showed significantly high loading owing to their large and dendritic pore structure. Among the tested DSNPs, pristine and phosphonate-modified DSNPs (PDSNPs) displayed remarkable loading of 40 and 35% w/w, respectively. Furthermore, particles successfully coated with positively charged chitosan reduced the burst release of exenatide at both pH 1.2 and 6.8. Compared with free exenatide, both chitosan-coated and uncoated PDSNPs enhanced exenatide transport through the Caco-2 monolayer by 1.7 fold. Interestingly, when a triple co-culture model of intestinal permeation was used, chitosan-coated PDSNPs performed better compared to both PDSNPs and free exenatide, which corroborated our hypothesis behind using chitosan to interact with mucus and improve permeation. These results indicate the emerging role of large pore silica nanoparticles as promising platforms for oral delivery of biologics such as exenatide. View Full-Text
Keywords: large pore silica nanoparticles; exenatide; oral delivery; anti-diabetic peptides large pore silica nanoparticles; exenatide; oral delivery; anti-diabetic peptides
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MDPI and ACS Style

Abeer, M.M.; Meka, A.K.; Pujara, N.; Kumeria, T.; Strounina, E.; Nunes, R.; Costa, A.; Sarmento, B.; Hasnain, S.Z.; Ross, B.P.; Popat, A. Rationally Designed Dendritic Silica Nanoparticles for Oral Delivery of Exenatide. Pharmaceutics 2019, 11, 418.

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