Abstract
Treatment of neovascular ocular diseases involves intravitreal injections of therapeutic proteins using conventional hypodermic needles every 4-6 weeks. Due to the chronic nature of these diseases, these injections will be administrated to patients for the rest of their lives and their frequent nature can potentially pose a risk of sight-threatening complications and poor patient compliance. Therefore, we propose to develop nanoparticle (NP)-loaded bilayer dissolving microneedle (MN) arrays, to sustain delivery of protein drugs in a minimally invasive manner. In this research, a model protein, ovalbumin (OVA)-encapsulated PLGA NPs were prepared and optimised using a water-in-oil-in-water (W/O/W) double emulsion method. The impact of stabilisers and primary sonication time on the stability of encapsulated OVA was evaluated using an enzyme-linked immunosorbent assay (ELISA). Results showed that the lower primary sonication time was capable of sustaining release (77 days at 28.5% OVA loading) and improving the OVA bioactivity. The optimised NPs were then incorporated into a polymeric matrix to fabricate bilayer MNs and specifically concentrated into MN tips by high-speed centrifugation. Optimised bilayer MNs exhibited good mechanical and insertion properties and rapid dissolution kinetics (less than 3 min) in excised porcine sclera. Importantly, ex vivo transscleral distribution studies conducted using a multiphoton microscope confirmed the important function of MN arrays in the localisation of proteins and NPs in the scleral tissue. Furthermore, the polymers selected to prepare bilayer MNs and OVA NPs were determined to be biocompatible with retinal cells (ARPE-19). This delivery approach could potentially sustain the release of encapsulated proteins for more than two months and effectively bypass the scleral barrier, leading to a promising therapy for treating neovascular ocular diseases.
Original language | English |
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Pages (from-to) | 306-318 |
Journal | European Journal of Pharmaceutics and Biopharmaceutics |
Volume | 165 |
Early online date | 26 May 2021 |
DOIs | |
Publication status | Published - Aug 2021 |
Keywords
- Bilayer microneedle
- Nanoparticle
- long-acting drug delivery
- ocular delivery
- posterior segment
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Dive into the research topics of 'Long-acting nanoparticle-loaded bilayer microneedles for protein delivery to the posterior segment of the eye'. Together they form a unique fingerprint.Student Theses
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Development of nanoparticle-loaded microneedles for protein and hydrophobic molecules delivery to the posterior segment of the eye
Author: Wu, Y., Jul 2022Supervisor: Thakur, R. (Supervisor) & Landa, E. L. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy
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Development of preformed photo-crosslinked intravitreal implants for protein delivery to the posterior segment of the eye
Author: Adrianto, M., Jul 2022Supervisor: Thakur, R. (Supervisor) & Donnelly, R. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy