Development of hybrid exosome-mimetic nanoparticles for eye disease
Topical instillation is the most common route of ocular drug delivery due to its ease of administration and high patient compliance. However, with the complex structure and numerous barriers of the eye, the bioavailability of drugs administered topically is <5%. Thus, there is a need to introd...
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| 格式: | Final Year Project |
| 語言: | English |
| 出版: |
Nanyang Technological University
2021
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| 主題: | |
| 在線閱讀: | https://hdl.handle.net/10356/148728 |
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| 總結: | Topical instillation is the most common route of ocular drug delivery due to its ease of
administration and high patient compliance. However, with the complex structure and
numerous barriers of the eye, the bioavailability of drugs administered topically is <5%. Thus,
there is a need to introduce a new drug delivery system for ocular medications to overcome the
low bioavailability.
Cell-derived nanovesicles (CDNs) are exosome-mimetic vesicles with a superior production
capability and possess membrane proteins that aid in cellular uptake. However, the CDNs
exhibit a negative surface charge and would experience electrostatic repulsion to the corneal
tissues. Consequently, the electrostatic repulsion would reduce the adsorption of the CDNs
onto the corneal surface, affecting their cellular uptake and permeation. Thus, in this study, the
aim was to hybridize CDNs with cationic materials to introduce a positive surface charge. This
was done by centrifugal serial extrusion.
Hybrid CDNs were synthesized using chitosan, polyallylamine hydrochloride (PAH), and
dioleoyl-3-trimethylammonium propane (DOTAP). The hybrid CDNs were then characterized
by nanoparticle tracking analysis and zeta potential (ZP), for hydrodynamic size and surface
charge, respectively. The hybridization was shown to reduce the negative surface charge of the
CDNs through the integration of cationic materials with the CDN membrane.
DOTAP and PAH had shown good integration with CDNs, creating cationic hybrid CDNs with
a zeta potential of 2.73 mV and 2.19 mV, respectively. Hence, DOTAP and PAH hybrid CDNs
have the potential to be used as an ocular drug delivery system. Although chitosan had
integrated with CDNs, the chitosan-hybrid CDNs failed to exhibit a positive ZP and were
deemed unsuitable for this application. |
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