June 2015
Volume 56, Issue 7
ARVO Annual Meeting Abstract  |   June 2015
Cubosomes nanoparticles for ocular delivery
Author Affiliations & Notes
  • Hong Zhang
    Ophthalmology, Ctr for Eye Resrch Australia, East Melbourne, VIC, Australia
    Eye Hospital, Harbin Medical University, Harbin, China
  • Jonathan P Wigg
    Ophthalmology, Ctr for Eye Resrch Australia, East Melbourne, VIC, Australia
  • Vicki Chrysostomou
    Ophthalmology, Ctr for Eye Resrch Australia, East Melbourne, VIC, Australia
  • Terence Hartnett
    Department of Chemical and Biomolecular Engineering, University of Melbourne, Melbourne, VIC, Australia
  • Footnotes
    Commercial Relationships Hong Zhang, None; Jonathan Wigg, None; Vicki Chrysostomou, None; Terence Hartnett, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 5033. doi:
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      Hong Zhang, Jonathan P Wigg, Vicki Chrysostomou, Terence Hartnett; Cubosomes nanoparticles for ocular delivery. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5033.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Intraocular injection is presently the only route of administration for large protein therapeutics; however this invasive intraocular procedure needs to be repeated frequently with potential risks. We hypothesized that bicontinuous, lyotrophic liquid crystalline phases and their dispersions (cubosomes) has the potential for the prolonged and safe delivery of large molecules into the eye. We tested this hypothesis in the present study.<br />

Methods: GMO - 1, 2 - dipalmitoyl phosphatidyl serine (DPPS) cubosomes was generated and stabilised using F127 and Pluronic® F108 (F108), a larger and more hydrophilic Pluronic® than F127. Particle size and polydispersity of the dispersions were characterized by dynamic light scattering size (DLS). A laboratory-built humidity-controlled vitrification system was used to prepare the samples for Cryo-TEM. The drug loading efficacy was also tested using the freeze-thaw technique. In vitro safety study was performed in SHSY, PRE and human scleral fibroblast cells (n=3). For in vivo safety testing, cubosomes was injected intravitreally or subconjunctivally in Sprague-Dawley rats (n=18), the functional and structural changes were evaluated by ERG and H&E staining. To test the sustained release profile, fluorescence loaded cubosomes were intravitreally injected into the eyes of Sprague-Dawley rats (n=3) and compared with the control group injected with fluorescence alone.

Results: Stabiliser selection is important as it influences the size and polydispersity of the cubosomes and demonstrate that the stability of these cubosomes is affected by changes in the temperature. In addition, we reveal that the use of F108 as a stabilising agent elicits a reduced toxic response in vitro compared to cubosomes stabilised with Pluronic® F127 (p<0.05). Encapsulation efficacy of FITC-BSA is 30 %. Intravitreal and Subconjunctival injections of 100ug/ml cubosome solutions into Rats have shown no evidence of changes to retinal function up to 3 months, nor changes to retinal layer thickness (p<0.05). We have also shown evidence of fluorescence labelled cubosomes in the ganglion cell layer after 24 hours after an intravitreal injection, however there was no fluorescence in the control group, suggesting the sustained release of fluorescence by cubosomes.

Conclusions: GMO - 1, 2 - dipalmitoyl phosphatidyl serine (DPPS) cubosomes can safely deliver large molecules into the eye and prolong the retention time of the drugs within the eye.


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