Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin

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Title: Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin-based nanoparticles designed to enhance intestinal delivery of insulin
Authors: Presas, Elena
McCartney, Fiona
Sultan, Eric
Brayden, David J.
et al.
Permanent link: http://hdl.handle.net/10197/10198
Date: 31-Jul-2018
Online since: 2019-04-29T11:49:46Z
Abstract: Due to excellent efficacy, low toxicity, and well-defined selectivity, development of new injectable peptides is increasing. However, the translation of these drugs into products for effective oral delivery has been restricted due to poor oral bioavailability. Nanoparticle (NP) formulations have potential to overcome the barriers to oral peptide delivery through protecting the payload and increasing bioavailability. This study describes the rational design, optimization and evaluation of a cyclodextrin-based NP entrapping insulin glulisine for intestinal administration. A cationic amphiphilic cyclodextrin (click propyl-amine cyclodextrin (CD)) was selected as the primary complexing agent for NP development. Following NP synthesis, in vitro characterization was performed. The insulin glulisine NPs exhibited an average size of 109 ± 9 nm, low polydispersity index (0.272) negative zeta potential (−25 ± 3 mV), high association efficiency (71.4 ± 3.37%) and an insulin loading of 10.2%. In addition, the NPs exhibited colloidal stability in intestinal-biorelevant media (SIF, supplemented-SIF 1% (w/v) and FaSSIF-V2) for up to 4 h. Proteolysis studies indicated that the NPs conferred protection to the entrapped insulin relative to free insulin. In vivo rat jejunal instillation studies demonstrated that the NPs mediated systemic insulin absorption, accompanied by a decrease in blood glucose levels. The relative bioavailability of the instilled insulin (50 IU/kg) from the NP was 5.5% compared to subcutaneous administration of insulin solution (1 IU/kg). The pharmacodynamic and pharmacokinetic data indicate that this cyclodextrin-based formulation may have potential for further research as an oral insulin dosage form.
Funding Details: European Commission - Seventh Framework Programme (FP7)
Type of material: Journal Article
Publisher: Elsevier
Journal: Journal of Controlled Release
Volume: 286
Start page: 402
End page: 414
Copyright (published version): 2018 Elsevier
Keywords: NanoparticlesCyclodextrinInsulinOral protein delivery
DOI: 10.1016/j.jconrel.2018.07.045
Language: en
Status of Item: Peer reviewed
Appears in Collections:Veterinary Medicine Research Collection
Veterinary Medicine Research Collection

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