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Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops

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Abstract

Glaucoma is a chronic progressive optic neuropathy that is characterized by optic nerve changes and visual field loss. Elevated intraocular pressure (IOP) is the main modifiable risk factor. Chronic instillation of daily eyedrops to lower IOP is the primary treatment of choice, although it requires patient adherence and correct performance. We have developed a nanoliposome drug delivery system for the longer term delivery of latanoprost. In the present open-label, pilot study, the safety and efficacy of a single subconjunctival injection of liposomal latanoprost was evaluated in six subjects with a diagnosis of either ocular hypertension (OHT) or primary open-angle glaucoma (POAG). Subconjunctival injection of liposomal latanoprost was well tolerated by all six subjects. From a baseline IOP of 27.55 ± 3.25 mmHg, the mean IOP decreased within 1 h to 14.52 ± 3.31 mmHg (range 10–18 mmHg). This represented a mean decrease of 13.03 ± 2.88 mmHg (range 9–17 mmHg), or 47.43 ± 10.05 % (range 37–63 %). A clinically and statistically significant IOP reduction (≥20 % IOP reduction, P = 0.001 to 0.049) was observed through 3 months after injection. The nanomedicine reported here is the first nanocarrier formulation that has an extended duration of action in humans, beyond a couple of weeks. The findings in this study open up a new treatment modality, which will greatly enhance patient compliance and improve treatment outcomes. The current study provides the evidence and support for further clinical studies of liposomal latanoprost in the treatment of glaucoma.

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Acknowledgement

R. S. Crockett, Ph.D. of D.A.T.A. Inc. for advice and support in statistical analysis. Ms Toh Ai Nee, clinical trial coordinator of the study, for ensuring a smooth process at every scheduled visit for the enrolled subjects. We thank the patients and families for their support and commitment to the study. This research was funded by the National Medical Research Council of Singapore, Translational Clinical Research grant no., NMRC/TCR/002-SERI/2008.

Conflict of interest

Tina Wong, Jayaganesh Natarajan and Subbu Venkatraman are named on the patent for the technology reported in the manuscript.

Gary Novack has received consultancy fees in the past 3 years from AbbVie, Inc., Aciont, Inc., Actelion, Acucela, Inc., Advanstar, Aerie Pharmaceuticals, Inc., Aerpio Therapeutics, Akebia, Alcon Laboratories, Alexion, Allergan Pharmaceuticals, Altacor, Ltd., Altheos, Inc., Amakem NV, Ampio, Apple Tree, Aquesys, Astellas Pharma Global Development, Astex, Aton Pharma, Inc., Auspex Pharmaceuticals, Inc., Avedro, Axar, Axon Advisors, Balance Therapeutics, Inc., BioGeneration Venture, Brickell Biotech, Inc., Calvert, Canaan Partners, Carlsbad Biotech, Celtic, Ceregene, Charlesson LLC, Chiltern, Clearside Biomedical, Concert Pharmaceuticals, Inc., Drais, Effcon Laboratories, Inc., EGS, Eleven Biotherapeutics, Elmedtech, LLC, Elsevier, Essex Woodlands, Ethis Communications, EyeCyte, Eyetech, Inc., Fidelity Biosciences, Fish & Richardson, Forest, Fovea Pharmaceuticals, Inc., Gerson Lehman Council, Glaukos, Inc., GREG, Harbor, Hatteras Partners, High Point Pharma, InnoPharma LLC, Innovent Biologics, InSite Vision, Inc., Inspire Pharmaceuticals, Inc., Investor Growth Capital, Inc., IOP, Inc., Johnson & Johnson, LEK Consulting LLC, Lexicon, Liquidia Technologies, Inc., Lithera (formerly Lipothera), Mati Therapeutics, Inc., Merck & Co., Mimetogen Pharmaceuticals, Mystic Pharmaceuticals, Nanyang Technical University (NTU), Nicox, NovaBay Pharmaceuticals, Inc., Novagali Pharma, Novartis, OcuCure Therapeutics, Inc., Ocular Theraputix, Inc., Ocularis Pharma, Omeros Corp., Ono Pharma USA, Onyx, OrbiMed Advisors, Panoptica, Inc., Parion Sciences, Inc., Perrigo Pharmaceuticals, PGTi Biosciences, Inc., Pieris, AG, Principia, Procter & Gamble, Promedior, Inc., QLT PhotoTherapeutics, Inc., Retina Pharmaceuticals, Inc., Rho Ventures, Rho, Inc., Santen Inc., SARCode, Senju Pharmaceutical Co., Ltd., Shire Pharmaceuticals, Inc., Sristek, Surmodics, Sylentis, Tear Film & Ocular Surface Society, Teva Pharmaceutical Industries, Thomas McNerney & Partners, Thrombogenics, Ltd., Usher III Initiative, Valeant, Velocity, Vistakon, Wells Fargo Securities, LLC, Xoma

Ching Lin Ho and Hla Myint Htoon declare they have no conflict of interest.

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Authors and Affiliations

  1. Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, Singapore, 168751

    Tina T. Wong & Hla M. Htoon

  2. Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, Singapore, 168751

    Tina T. Wong & Ching Lin Ho

  3. School of Materials Science and Engineering, Nanyang Technological University, Blk N4.1, Nanyang Avenue, Singapore, Singapore, 639798

    Tina T. Wong, Jayaganesh V. Natarajan & Subbu S. Venkatraman

  4. PharmaLogic Development Inc., San Rafael, CA, USA

    Gary D. Novack

Authors
  1. Tina T. Wong
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  2. Gary D. Novack
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  3. Jayaganesh V. Natarajan
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  4. Ching Lin Ho
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  5. Hla M. Htoon
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  6. Subbu S. Venkatraman
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Corresponding authors

Correspondence to Tina T. Wong or Subbu S. Venkatraman.

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Wong, T.T., Novack, G.D., Natarajan, J.V. et al. Nanomedicine for glaucoma: sustained release latanoprost offers a new therapeutic option with substantial benefits over eyedrops. Drug Deliv. and Transl. Res. 4, 303–309 (2014). https://doi.org/10.1007/s13346-014-0196-9

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  • DOI: https://doi.org/10.1007/s13346-014-0196-9

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