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RESEARCH ARTICLE
Contents Vol 73(10)

Encapsulation and Controlled Release of the Therapeutic Neuropeptides Somatostatin and Oxytocin from the Lipidic Bicontinuous Cubic Phase

Jamie B. Strachan A , Durga Dharmadana A B , Brendan P. Dyett A , Céline Valéry B and Charlotte E. Conn https://orcid.org/0000-0002-3362-3453 A C
+ Author Affiliations
- Author Affiliations

A School of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Vic. 3000, Australia.

B School of Health and Biomedical Sciences, Translational Immunology and Nanotechnology Research Program, College of Science, Engineering and Health, RMIT University, Melbourne, Vic. 3083, Australia.

C Corresponding author. Email: charlotte.conn@rmit.edu.au

Australian Journal of Chemistry 73(10) 1042-1050 https://doi.org/10.1071/CH19573
Submitted: 4 November 2019  Accepted: 17 April 2020   Published: 17 June 2020

Abstract

Therapeutic delivery of neuropeptides including oxytocin and somatostatin is associated with numerous difficulties including low stability, low oral bioavailability, and a short half-life in vivo. For delivery to the brain, these issues are exacerbated by difficulties in crossing the blood–brain barrier. Lipid-based nanomaterials may offer specific advantages for the delivery of therapeutic peptides including good biocompatibility, retention of peptide activity, and controlled release properties. Herein we have investigated the use of the lipid bicontinuous cubic phase as a depot formulation for the controlled release of the neuropeptides oxytocin and somatostatin. Retention of the cubic architecture was confirmed up to high peptide concentrations of at least 30 mg mL−1 for both peptides. Encapsulation had only minimal effect on the peptide secondary structure in both cases. Controlled release of the peptides from the cubic phase was diffusion controlled over the first 24 h. The time-dependent self-assembly of somatostatin into nanofibrils within the bicontinuous cubic phase led to a unique two-stage release mechanism, with diffusion-controlled release of the peptide monomer over the first 24 h followed by a much slower linear release of the peptide from the nanofibrils. Results suggest that the lipid bicontinuous cubic phase is a highly prospective nanomaterial for the encapsulation and controlled release of neuropeptide therapeutics.


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