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

2014 ◽  
Vol 8 (2) ◽  
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.

scholarly journals Design of an Implantable Device for Ocular Drug Delivery

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jae-Hwan Lee ◽  
Ramana M. Pidaparti ◽  
Gary M. Atkinson ◽  
Ramana S. Moorthy
Keyword(s):  
Drug Delivery ◽  
Ocular Drug Delivery ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Drug Management ◽  
Drug Delivery Device ◽  
Age Related ◽  
Diffusion Characteristics ◽  
Drug Reservoir ◽  
Silicon Based

Ocular diseases, such as, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy, and retinitis pigmentosa require drug management in order to prevent blindness and affecting million of adults in USA and worldwide. There is an increasing need to develop devices for drug delivery to address ocular diseases. This study focuses on the design, simulation, and development of an implantable ocular drug delivery device consisting of micro-/nanochannels embedded between top and bottom covers with a drug reservoir made from polydimethylsiloxane (PDMS) which is silicon-based organic and biodegradable polymer. Several simulations were carried out with six different micro-channel configurations in order to see the feasibility for ocular drug delivery applications. Based on the results obtained, channel design of osmotic I and osmotic II satisfied the diffusion rates required for ocular drug delivery. Finally, a prototype illustrating the three components of the drug delivery design is presented. In the future, the device will be tested for its functionality and diffusion characteristics.

An Implantable Device Design Concept for Ocular Drug Delivery

2012 ◽  
Author(s):  
Jae-Hwan Lee ◽  
Ramana M. Pidaparti
Keyword(s):  
Drug Delivery ◽  
Macular Degeneration ◽  
Ocular Drug Delivery ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Intravitreal Injections ◽  
Delivery Device ◽  
Drug Delivery Device ◽  
Age Related ◽  
Intraocular Hemorrhage

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.

Nanotechnology for Omics-Based Ocular Drug Delivery

Oncology ◽  
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.

scholarly journals Nanotechnology for Omics-Based Ocular Drug Delivery

Ophthalmology ◽  
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.

Nanotechnology for Omics-Based Ocular Drug Delivery

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.

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

Pharmaceutics ◽  
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.

Oxidative Stress, Ocular Disease and Diabetes Retinopathy

2019 ◽  
Vol 24 (40) ◽  
pp. 4726-4741 ◽  
Author(s):  
Orathai Tangvarasittichai ◽  
Surapon Tangvarasittichai
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Death ◽  
Protein Modification ◽  
Morphological Changes ◽  
Corneal Dystrophy ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Retinal Light Damage ◽  
Age Related

Background: Oxidative stress is caused by free radicals or oxidant productions, including lipid peroxidation, protein modification, DNA damage and apoptosis or cell death and results in cellular degeneration and neurodegeneration from damage to macromolecules. Results: Accumulation of the DNA damage (8HOdG) products and the end products of LPO (including aldehyde, diene, triene conjugates and Schiff’s bases) were noted in the research studies. Significantly higher levels of these products in comparison with the controls were observed. Oxidative stress induced changes to ocular cells and tissues. Typical changes include ECM accumulation, cell dysfunction, cell death, advanced senescence, disarrangement or rearrangement of the cytoskeleton and released inflammatory cytokines. It is involved in ocular diseases, including keratoconus, Fuchs endothelial corneal dystrophy, and granular corneal dystrophy type 2, cataract, age-related macular degeneration, primary open-angle glaucoma, retinal light damage, and retinopathy of prematurity. These ocular diseases are the cause of irreversible blindness worldwide. Conclusions: Oxidative stress, inflammation and autophagy are implicated in biochemical and morphological changes in these ocular tissues. The development of therapy is a major target for the management care of these ocular diseases.

Advanced Hydrogels Based Drug Delivery Systems for Ophthalmic Delivery

2020 ◽  
Vol 13 (4) ◽  
pp. 291-300 ◽  
Author(s):  
Srividya Gorantla ◽  
Tejashree Waghule ◽  
Vamshi Krishna Rapalli ◽  
Prem Prakash Singh ◽  
Sunil Kumar Dubey ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Age Related Macular Degeneration ◽  
Stimuli Responsive ◽  
Duration Of Action ◽  
Age Related ◽  
Aqueous Gels ◽  
Ophthalmic Delivery ◽  
3D Printed

Hydrogels are aqueous gels composed of cross-linked networks of hydrophilic polymers. Stimuli-responsive based hydrogels have gained focus over the past 20 years for treating ophthalmic diseases. Different stimuli-responsive mechanisms are involved in forming polymer hydrogel networks, including change in temperature, pH, ions, and others including light, thrombin, pressure, antigen, and glucose-responsive. Incorporation of nanocarriers with these smart stimuli-responsive drug delivery systems that can extend the duration of action by increasing ocular bioavailability and reducing the dosing frequency. This review will focus on the hydrogel drug delivery systems highlighting the gelling mechanisms and emerging stimuli-responsive hydrogels from preformed gels, nanogels, and the role of advanced 3D printed hydrogels in vision-threatening diseases like age-related macular degeneration and retinitis pigmentosa. It also provides insight into the limitations of hydrogels along with the safety and biocompatibility of the hydrogel drug delivery systems.

scholarly journals Nanocarriers, Progenitor Cells, Combinational Approaches, and New Insights on the Retinal Therapy

2021 ◽  
Vol 22 (4) ◽  
pp. 1776
Author(s):  
Elham Pishavar ◽  
Hongrong Luo ◽  
Johanna Bolander ◽  
Antony Atala ◽  
Seeram Ramakrishna
Keyword(s):  
Drug Delivery ◽  
Progenitor Cells ◽  
Transfection Efficiency ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Therapeutic Approaches ◽  
Age Related ◽  
Nanofibrous Scaffolds ◽  
The Stability

Progenitor cells derived from the retinal pigment epithelium (RPECs) have shown promise as therapeutic approaches to degenerative retinal disorders including diabetic retinopathy, age-related macular degeneration and Stargardt disease. However, the degeneration of Bruch’s membrane (BM), the natural substrate for the RPE, has been identified as one of the major limitations for utilizing RPECs. This degeneration leads to decreased support, survival and integration of the transplanted RPECs. It has been proposed that the generation of organized structures of nanofibers, in an attempt to mimic the natural retinal extracellular matrix (ECM) and its unique characteristics, could be utilized to overcome these limitations. Furthermore, nanoparticles could be incorporated to provide a platform for improved drug delivery and sustained release of molecules over several months to years. In addition, the incorporation of tissue-specific genes and stem cells into the nanostructures increased the stability and enhanced transfection efficiency of gene/drug to the posterior segment of the eye. This review discusses available drug delivery systems and combination therapies together with challenges associated with each approach. As the last step, we discuss the application of nanofibrous scaffolds for the implantation of RPE progenitor cells with the aim to enhance cell adhesion and support a functionally polarized RPE monolayer.

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