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Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection

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ABSTRACT

Purpose

RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina.

Methods

Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double-stranded RNA (dsRNA) were administered via subconjunctival injection in mice. Alexa647 dye was a control. Topical administration was performed for comparison. Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed using whole-body fluorescence imaging of the eyes. The numbers of cells in the ocular tissues with nanoparticle cell internalization were determined in fluorescence microscopy of dissected eye tissues.

Results

After subconjunctival injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of the retina. Topical administration was not effective in delivering the nanoparticles to the eye.

Conclusions

The pRNA nanoparticles were delivered to the cells in the eye via subconjunctival injection, and cell internalization was achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X. Only the X-shape pRNA-X could enter the retina.

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ACKNOWLEDGMENTS AND DISCLOSURES

This paper is dedicated to Dr. Stephen J. Ryan, the founder of the Arnold and Mabel Beckman Initiative for Macular Research. The research was supported in part by NCI Cancer Nanotechnology Platform Partnership Program: RNA Nanotechnology for Cancer Therapy, as the NIH U01 CA151648 program directed by Peixuan Guo; and Beckman Initiative for Macular Research Grant 1108 (to Peixuan Guo) as well as 1210 (to David Gamm and Dan Shu). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Funding to P. Guo's Endowed Chair in Nanobiotechnology position is by the William Fairish Endowment Fund. P. Guo is a co-founder of Kylin Therapeutics, Inc., and Biomotor and Nucleic Acid Nanotechnology Development Corp. Ltd.. The authors thank Drs. Winston W-Y. Kao and Ying Xia for providing the AxioCam Observer Z1 microscopes in the study; Dr. Jinsong Hao for her technical support; and Dr. Jiukuan Hao for helpful discussion. The authors also thank Drs. Maria B. Grant for collaboration and discussion; David Gamm, Michael Boulton, and Mark Humayun for constructive comments and inspiring discussion.

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Authors and Affiliations

  1. Division of Pharmaceutical Sciences James L. Winkle College of Pharmacy, University of Cincinnati, 3225 Eden Avenue 136 HPB, Cincinnati, Ohio, 45267, USA

    Liang Feng & S. Kevin Li

  2. Department of Ophthalmology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, 45267, USA

    Hongshan Liu & Chia-Yang Liu

  3. Vontz Core Imaging Laboratory (VCIL), University of Cincinnati, Cincinnati, Ohio, 45267, USA

    Kathleen LaSance

  4. Department of Pharmaceutical Sciences School of Pharmacy and Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40536, USA

    Farzin Haque, Dan Shu & Peixuan Guo

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  1. Liang Feng
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Correspondence to S. Kevin Li.

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Feng, L., Li, S.K., Liu, H. et al. Ocular Delivery of pRNA Nanoparticles: Distribution and Clearance After Subconjunctival Injection. Pharm Res 31, 1046–1058 (2014). https://doi.org/10.1007/s11095-013-1226-x

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  • DOI: https://doi.org/10.1007/s11095-013-1226-x

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