Diamond Nanogel-Embedded Contact Lenses Mediate Lysozyme-Dependent Therapeutic Release

Temporarily implanted devices, such as drug-loaded contact lenses, are emerging as the preferred treatment method for ocular diseases like glaucoma. Localizing the delivery of glaucoma drugs, such as timolol maleate (TM), can minimize adverse effects caused by systemic administration. Although eye drops and drug-soaked lenses allow for local treatment, their utility is limited by burst release and a lack of sustained therapeutic delivery. Additionally, wet transportation and storage of drug-soaked lenses result in drug loss due to elution from the lenses. Here we present a nanodiamond (ND)-embedded contact lens capable of lysozyme-triggered release of TM for sustained therapy. We find that ND-embedded lenses composed of enzyme-cleavable polymers allow for controlled and sustained release of TM in the presence of lysozyme. Retention of drug activity is verified in primary human trabecular meshwork cells. These results demonstrate the translational potential of an ND-embedded lens capable of drug sequestration and enzyme activation.

[1]  Dean Ho,et al.  Diamond‐Lipid Hybrids Enhance Chemotherapeutic Tolerance and Mediate Tumor Regression , 2013, Advanced materials.

[2]  F. Caruso,et al.  Enzyme encapsulation in layer-by-layer engineered polymer multilayer capsules. , 2000 .

[3]  Robert Langer,et al.  Preclinical Development and Clinical Translation of a PSMA-Targeted Docetaxel Nanoparticle with a Differentiated Pharmacological Profile , 2012, Science Translational Medicine.

[4]  Dean Ho,et al.  Gd(III)-nanodiamond conjugates for MRI contrast enhancement. , 2010, Nano letters.

[5]  Erik Pierstorff,et al.  Nanodiamond-embedded microfilm devices for localized chemotherapeutic elution. , 2008, ACS nano.

[6]  J. Tour,et al.  Effective drug delivery, in vitro and in vivo, by carbon-based nanovectors noncovalently loaded with unmodified Paclitaxel. , 2010, ACS nano.

[7]  M. Morales i Ballús,et al.  The number of people with glaucoma worldwide in 2010 and 2020 , 2006 .

[8]  Antonios Kontsos,et al.  Mechanical properties and biomineralization of multifunctional nanodiamond-PLLA composites for bone tissue engineering. , 2012, Biomaterials.

[9]  Takeshi Azami,et al.  Toxicity of single-walled carbon nanohorns. , 2008, ACS nano.

[10]  R. Langer,et al.  A drug-eluting contact lens. , 2009, Investigative ophthalmology & visual science.

[11]  Dean Ho,et al.  Cancer Nanomedicine: From Drug Delivery to Imaging , 2013, Science Translational Medicine.

[12]  Yolanda Diebold,et al.  Applications of nanoparticles in ophthalmology , 2010, Progress in Retinal and Eye Research.

[13]  J. Avorn,et al.  Treatment for glaucoma: adherence by the elderly. , 1993, American journal of public health.

[14]  Q. Garrett,et al.  Hydrogel lens monomer constituents modulate protein sorption. , 2000, Investigative ophthalmology & visual science.

[15]  Lei Tao,et al.  A comparative study of cellular uptake and cytotoxicity of multi-walled carbon nanotubes, graphene oxide, and nanodiamond , 2012 .

[16]  Carmen Alvarez-Lorenzo,et al.  Ocular release of timolol from molecularly imprinted soft contact lenses. , 2005, Biomaterials.

[17]  Steven Castleberry,et al.  Nanolayered siRNA dressing for sustained localized knockdown. , 2013, ACS nano.

[18]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[19]  N. Rozhkova,et al.  Consequences of strong and diverse electrostatic potential fields on the surface of detonation nanodiamond particles , 2009 .

[20]  A. Izzotti,et al.  Ability of dorzolamide hydrochloride and timolol maleate to target mitochondria in glaucoma therapy. , 2011, Archives of ophthalmology.

[21]  Yury Gogotsi,et al.  Fluorescent PLLA-nanodiamond composites for bone tissue engineering. , 2011, Biomaterials.

[22]  Eiji Osawa,et al.  Confirmation of the electrostatic self-assembly of nanodiamonds. , 2011, Nanoscale.

[23]  Xiaojun Ma,et al.  The enzymatic degradation and swelling properties of chitosan matrices with different degrees of N-acetylation. , 2005, Carbohydrate research.

[24]  H. Quigley,et al.  The number of people with glaucoma worldwide in 2010 and 2020 , 2006, British Journal of Ophthalmology.

[25]  Tim Liedl,et al.  Nanoengineered polymer capsules: tools for detection, controlled delivery, and site-specific manipulation. , 2005, Small.

[26]  Huan-Cheng Chang,et al.  Tracking the Engraftment and Regenerative Capabilities of Transplanted Lung Stem Cells using Fluorescent Nanodiamonds , 2014 .

[27]  A. Chauhan,et al.  Temperature sensitive contact lenses for triggered ophthalmic drug delivery. , 2012, Biomaterials.

[28]  Ashish A. Pandya,et al.  Rapidly–Dissolvable Microneedle Patches Via a Highly Scalable and Reproducible Soft Lithography Approach , 2013, Advanced materials.

[29]  Betty Y. S. Kim,et al.  Advances and challenges of nanotechnology-based drug delivery systems , 2007, Expert opinion on drug delivery.

[30]  D. Irvine,et al.  Layer-by-layer-assembled multilayer films for transcutaneous drug and vaccine delivery. , 2009, ACS nano.

[31]  Po-Ying Li,et al.  An electrochemical intraocular drug delivery device , 2008, 2007 IEEE 20th International Conference on Micro Electro Mechanical Systems (MEMS).

[32]  Priscilla Kailian Ang,et al.  Supported Lipid Bilayer on Nanocrystalline Diamond: Dual Optical and Field‐Effect Sensor for Membrane Disruption , 2009 .

[33]  Benjamin C. Tang,et al.  Mucus-Penetrating Nanoparticles for Vaginal Drug Delivery Protect Against Herpes Simplex Virus , 2012, Science Translational Medicine.

[34]  Hu Yang,et al.  Hybrid dendrimer hydrogel/PLGA nanoparticle platform sustains drug delivery for one week and antiglaucoma effects for four days following one-time topical administration. , 2012, ACS nano.

[35]  Ali Khademhosseini,et al.  Development of functional biomaterials with micro‐ and nanoscale technologies for tissue engineering and drug delivery applications , 2014, Journal of tissue engineering and regenerative medicine.

[36]  Chia‐Chen Li,et al.  Preparation of clear colloidal solutions of detonation nanodiamond in organic solvents , 2010 .

[37]  Tejal A Desai,et al.  Nanostructure-mediated transport of biologics across epithelial tissue: enhancing permeability via nanotopography. , 2013, Nano letters.

[38]  K. Anseth,et al.  Poly(ethylene glycol) hydrogels formed by thiol-ene photopolymerization for enzyme-responsive protein delivery. , 2009, Biomaterials.

[39]  E. Lavik,et al.  Sustained delivery of timolol maleate from poly(lactic-co-glycolic acid)/poly(lactic acid) microspheres for over 3 months , 2008, Journal of microencapsulation.

[40]  Young H. Kwon,et al.  Novel drug delivery systems for glaucoma , 2011, Eye.

[41]  Thisbe K Lindhorst,et al.  Saccharide-modified nanodiamond conjugates for the efficient detection and removal of pathogenic bacteria. , 2012, Chemistry.

[42]  A. Goga,et al.  Nanodiamond Therapeutic Delivery Agents Mediate Enhanced Chemoresistant Tumor Treatment , 2011, Science Translational Medicine.

[43]  Yury Gogotsi,et al.  The properties and applications of nanodiamonds. , 2011, Nature nanotechnology.

[44]  Robert Langer,et al.  Impact of nanotechnology on drug delivery. , 2009, ACS nano.

[45]  S. Withers,et al.  Catalysis by hen egg-white lysozyme proceeds via a covalent intermediate , 2001, Nature.

[46]  David J. Mooney,et al.  Active scaffolds for on-demand drug and cell delivery , 2010, Proceedings of the National Academy of Sciences.

[47]  Lyndon Jones,et al.  Nanomaterials for ocular drug delivery. , 2012, Macromolecular bioscience.

[48]  Anuj Chauhan,et al.  Extended drug delivery by contact lenses for glaucoma therapy. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[49]  A. Chauhan,et al.  Extended release of timolol from nanoparticle-loaded fornix insert for glaucoma therapy. , 2013, Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics.