Design of an Implantable Device for Ocular Drug Delivery

New drugs for curing eye diseases have been developing for a decade and are very unique for each eye diseases such as glaucoma, cataracts, and age-related macular degeneration (AMD). It is estimated that 1.6 million adults in the US over the age of 50 and above suffer from age-related macular degeneration and about 200,000 cases are diagnosed annually. Worldwide, about 500,000 cases are diagnosed annually [1]. Drugs currently utilized for AMD are delivered via repeated intravitreal injections of the drug into the eye. Risks of repeated intravitreal injections can include intraocular infections (endophthalmitis), intraocular hemorrhage, and retinal detachment. Also, reducing the frequency of dosing will clearly benefit the patient by reducing the need for risky intravitreal injections and improving the pharmacokinetics of the drug in the eye. The eye disease of posterior segment (Dry and Wet) has limits to deliver the drug to retina region using typical eye drop. The drug injection using a needle with syringe can deliver but it barely provide right amount of doses, or over doses that may cause more severe problem such as swelling, fatigue, and damaging photoreceptor molecules. Furthermore, most drugs run away in a month so that repeated injection is necessary. Developing an implantable drug delivery device will help reduce the costs and risks associated with frequent injections and facilitate delivering the drug in a controlled manner and in the required amounts, and improve therapeutic efficacy and safety of drugs. This study focuses on the design, simulation and development of the implantable ocular drug delivery device.

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Design Optimization of an Implantable Device Concept for Passive Ocular Drug Delivery

Journal of Medical Devices ◽

10.1115/1.4026451 ◽

2014 ◽

Vol 8 (2) ◽

Cited By ~ 4

Author(s):

Jonathan Marsh ◽

Ramana M. Pidaparti

Keyword(s):

Drug Delivery ◽

Drug Transport ◽

Implantable Device ◽

Age Related Macular Degeneration ◽

Design Parameters ◽

Ocular Diseases ◽

Drug Delivery Device ◽

Age Related ◽

Optimization Study ◽

Dynamics Simulations

This paper presents an implantable device concept with applications for treating ocular diseases such as glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa. The design of a biodegradable drug delivery device concept consisting of a polydimethylsiloxane (PDMS) shell with a fluid reservoir and micro/nanofluidic tubes that allow the drug to be stored and delivered at a specified rate is discussed. Computational fluid dynamics simulations were conducted through various tube configurations in order to obtain the drug diffusion characteristics. The results from the simulation studies revealed information related to drug transport under varying design parameters. The design simulations were conducted with a desired rate. Based on results from several simulations, an optimization study was conducted to achieve the required dosage for about 2 years. The results obtained from the optimization study shows that the device concept can be extended for different drugs to treat ocular diseases.

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Nanotechnology for Omics-Based Ocular Drug Delivery

Oncology ◽

10.4018/978-1-5225-0549-5.ch013 ◽

2017 ◽

pp. 366-381

Author(s):

Anjali Hirani ◽

Aditya Grover ◽

Yong Woo Lee ◽

Yashwant Pathak ◽

Vijaykumar Sutariya

Keyword(s):

Drug Delivery ◽

Molecular Markers ◽

Drug Delivery Systems ◽

Diagnostic Techniques ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Age Related ◽

Conventional Drug ◽

Genomics And Proteomics ◽

Translational Level

Millions of people suffer from ocular diseases that impair vision and can lead to blindness. Advances in genomics and proteomics have revealed a number of different molecular markers specific for different ocular diseases, thereby optimizing the processes of drug development and discovery. Nanotechnology can increase the throughput of data obtained in omics-based studies and allows for more sensitive diagnostic techniques as more efficient drug delivery systems. Biocompatible and biodegradable nanomaterials developed through omics-based research are able to target reported molecular markers for different ocular diseases and offer novel alternatives to conventional drug therapy. In this chapter, the authors review the pathophysiology, current genomic and proteomic information, and current nanomaterial-based therapies of four ocular diseases: glaucoma, uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Omics-based research can be used to elucidate specific genes and proteins and develop novel nanomedicine formulations to prevent, halt, or cure ocular diseases at the transcriptional or translational level.

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Nanotechnology for Omics-Based Ocular Drug Delivery

Ophthalmology ◽

10.4018/978-1-5225-5195-9.ch017 ◽

2018 ◽

pp. 283-298

Author(s):

Anjali Hirani ◽

Aditya Grover ◽

Yong Woo Lee ◽

Yashwant Pathak ◽

Vijaykumar Sutariya

Keyword(s):

Drug Delivery ◽

Molecular Markers ◽

Drug Delivery Systems ◽

Diagnostic Techniques ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Age Related ◽

Conventional Drug ◽

Genomics And Proteomics ◽

Translational Level

Millions of people suffer from ocular diseases that impair vision and can lead to blindness. Advances in genomics and proteomics have revealed a number of different molecular markers specific for different ocular diseases, thereby optimizing the processes of drug development and discovery. Nanotechnology can increase the throughput of data obtained in omics-based studies and allows for more sensitive diagnostic techniques as more efficient drug delivery systems. Biocompatible and biodegradable nanomaterials developed through omics-based research are able to target reported molecular markers for different ocular diseases and offer novel alternatives to conventional drug therapy. In this chapter, the authors review the pathophysiology, current genomic and proteomic information, and current nanomaterial-based therapies of four ocular diseases: glaucoma, uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Omics-based research can be used to elucidate specific genes and proteins and develop novel nanomedicine formulations to prevent, halt, or cure ocular diseases at the transcriptional or translational level.

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Nanotechnology for Omics-Based Ocular Drug Delivery

Handbook of Research on Diverse Applications of Nanotechnology in Biomedicine, Chemistry, and Engineering - Advances in Chemical and Materials Engineering ◽

10.4018/978-1-4666-6363-3.ch008 ◽

2015 ◽

pp. 152-166

Author(s):

Anjali Hirani ◽

Aditya Grover ◽

Yong Woo Lee ◽

Yashwant Pathak ◽

Vijaykumar Sutariya

Keyword(s):

Drug Delivery ◽

Molecular Markers ◽

Drug Delivery Systems ◽

Diagnostic Techniques ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Age Related ◽

Conventional Drug ◽

Genomics And Proteomics ◽

Translational Level

Millions of people suffer from ocular diseases that impair vision and can lead to blindness. Advances in genomics and proteomics have revealed a number of different molecular markers specific for different ocular diseases, thereby optimizing the processes of drug development and discovery. Nanotechnology can increase the throughput of data obtained in omics-based studies and allows for more sensitive diagnostic techniques as more efficient drug delivery systems. Biocompatible and biodegradable nanomaterials developed through omics-based research are able to target reported molecular markers for different ocular diseases and offer novel alternatives to conventional drug therapy. In this chapter, the authors review the pathophysiology, current genomic and proteomic information, and current nanomaterial-based therapies of four ocular diseases: glaucoma, uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Omics-based research can be used to elucidate specific genes and proteins and develop novel nanomedicine formulations to prevent, halt, or cure ocular diseases at the transcriptional or translational level.

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Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

Journal of Drug Delivery ◽

10.1155/2016/7913616 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Marcus J. Goudie ◽

Alyssa P. Ghuman ◽

Stephanie B. Collins ◽

Ramana M. Pidaparti ◽

Hitesh Handa

Keyword(s):

Drug Delivery ◽

Surface Chemistry ◽

Soft Lithography ◽

Age Related Macular Degeneration ◽

Delivery Rate ◽

Microfluidic Channels ◽

Age Related ◽

Diffusion Characteristics ◽

Drug Delivery Applications ◽

Model Drug

Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug.

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Suprachoroidal Delivery of Small Molecules, Nanoparticles, Gene and Cell Therapies for Ocular Diseases

Pharmaceutics ◽

10.3390/pharmaceutics13020288 ◽

2021 ◽

Vol 13 (2) ◽

pp. 288

Author(s):

Chen-rei Wan ◽

Leroy Muya ◽

Viral Kansara ◽

Thomas A. Ciulla

Keyword(s):

Drug Delivery ◽

Gene Therapy ◽

Small Molecules ◽

Small Molecule ◽

Viral Vector ◽

Choroidal Melanoma ◽

Therapeutic Agents ◽

Age Related Macular Degeneration ◽

Ocular Diseases ◽

Age Related

Suprachoroidal drug delivery technology has advanced rapidly and emerged as a promising administration route for a variety of therapeutic candidates, in order to target multiple ocular diseases, ranging from neovascular age-related macular degeneration to choroidal melanoma. This review summarizes the latest preclinical and clinical progress in suprachoroidal delivery of therapeutic agents, including small molecule suspensions, polymeric entrapped small molecules, gene therapy (viral and nonviral nanoparticles), viral nanoparticle conjugates (VNCs), and cell therapy. Formulation customization is critical in achieving favorable pharmacokinetics, and sustained drug release profiles have been repeatedly observed for multiple small molecule suspensions and polymeric formulations. Novel therapeutic agents such as viral and nonviral gene therapy, as well as VNCs, have demonstrated promise in animal studies. Several of these suprachoroidally-administered therapies have been assessed in clinical trials, including small molecule suspensions of triamcinolone acetonide and axitinib, viral vector RGX-314 for gene therapy, and VNC AU-011. With continued drug delivery research and optimization, coupled with customized drug formulations, suprachoroidal drug delivery may address large unmet therapeutic needs in ophthalmology, targeting affected tissues with novel therapies for efficacy benefits, compartmentalizing therapies away from unaffected tissues for safety benefits, and achieving durability to relieve the treatment burden noted with current agents.

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Biofabrication of Chitosan-Based Nanomedicines and Its Potential Use for Translational Ophthalmic Applications

Applied Sciences ◽

10.3390/app10124189 ◽

2020 ◽

Vol 10 (12) ◽

pp. 4189

Author(s):

Riddhi Vichare ◽

Inyoung Garner ◽

Ryan J. Paulson ◽

Radouil Tzekov ◽

Nurettin Sahiner ◽

...

Keyword(s):

Drug Delivery ◽

Chitosan Nanoparticles ◽

Drug Carriers ◽

Ocular Drug Delivery ◽

Age Related Macular Degeneration ◽

In Vivo Studies ◽

Sustained Drug Release ◽

Release Formulation ◽

Vast Number ◽

Age Related

Drug delivery to the anterior and posterior segment of eye remains a challenge. Nanoparticle-mediated drug delivery has indicated some promise. The presented review aims to summarize recent advancements in chitosan-based nanotherapies for ocular drug delivery and the challenges encountered during the process. Significant research using chitosan, a cationic linear polymer, is being conducted for ocular drug delivery. A vast number of publications exploit the mucoadhesive properties of the polymer, which arise due to interactions between the amino acids of chitosan and the sialic acid residues in mucous. The high degree of crosslinking in chitosan nanoparticles facilitates a dramatic increase in ocular drug retention of the desired drug, which subsequently helps in ocular penetration and improving the bioavailability of the drugs. A noted decrease in the initial burst of the drug is the basis for developing sustained drug release formulation using biodegradable and biocompatible chitosan polymer. In vitro as well as in vivo studies have indicated enhancement in the uptake, accumulation, and removal of chitosan nanoparticles from the site of delivery. In summary, chitosan- or modified-chitosan-based nanoparticles are being widely tested as drug carriers for treatment of bacterial and viral infections, glaucoma, age-related macular degeneration, and diabetic retinopathy.

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Ocular Drug Delivery to the Retina: Current Innovations and Future Perspectives

Pharmaceutics ◽

10.3390/pharmaceutics13010108 ◽

2021 ◽

Vol 13 (1) ◽

pp. 108

Author(s):

Hyeong Min Kim ◽

Se Joon Woo

Keyword(s):

Drug Delivery ◽

Treatment Options ◽

Drug Efficacy ◽

Delivery Systems ◽

Ocular Drug Delivery ◽

Age Related Macular Degeneration ◽

Future Perspectives ◽

Age Related ◽

Invasive Techniques

Treatment options for retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vascular disorders, have markedly expanded following the development of anti-vascular endothelial growth factor intravitreal injection methods. However, because intravitreal treatment requires monthly or bimonthly repeat injections to achieve optimal efficacy, recent investigations have focused on extended drug delivery systems to lengthen the treatment intervals in the long term. Dose escalation and increasing molecular weight of drugs, intravitreal implants and nanoparticles, hydrogels, combined systems, and port delivery systems are presently under preclinical and clinical investigations. In addition, less invasive techniques rather than intravitreal administration routes, such as topical, subconjunctival, suprachoroidal, subretinal, and trans-scleral, have been evaluated to reduce the treatment burden. Despite the latest advancements in the field of ophthalmic pharmacology, enhancing drug efficacy with high ocular bioavailability while avoiding systemic and local adverse effects is quite challenging. Consequently, despite the performance of numerous in vitro studies, only a few techniques have translated to clinical trials. This review discusses the recent developments in ocular drug delivery to the retina, the pharmacokinetics of intravitreal drugs, efforts to extend drug efficacy in the intraocular space, minimally invasive techniques for drug delivery to the retina, and future perspectives in this field.

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