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.

scholarly journals Nanotechnology for Age-Related Macular Degeneration

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2035
Author(s):  
Bo Yang ◽  
Ge Li ◽  
Jiaxin Liu ◽  
Xiangyu Li ◽  
Shixin Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Gene Therapy ◽  
Macular Degeneration ◽  
Vision Loss ◽  
Cumulative Risk ◽  
Age Related Macular Degeneration ◽  
Delivery Methods ◽  
Age Related ◽  
Therapy Strategies ◽  
Endothelial Growth Factor

Age-related macular degeneration (AMD) is a degenerative eye disease that is the leading cause of irreversible vision loss in people 50 years and older. Today, the most common treatment for AMD involves repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, the existing expensive therapies not only cannot cure this disease, they also produce a variety of side effects. For example, the number of injections increases the cumulative risk of endophthalmitis and other complications. Today, a single intravitreal injection of gene therapy products can greatly reduce the burden of treatment and improve visual effects. In addition, the latest innovations in nanotherapy provide the best drug delivery alternative for the treatment of AMD. In this review, we discuss the development of nano-drug delivery systems and gene therapy strategies for AMD in recent years. In addition, we discuss some novel targeting strategies and the potential application of these delivery methods in the treatment of AMD. Finally, we also propose that the combination of CRISPR/Cas9 technology with a new non-viral delivery system may be promising as a therapeutic strategy for the treatment of AMD.

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.

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.

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 Ocular Therapeutics and Molecular Delivery Strategies for Neovascular Age-Related Macular Degeneration (nAMD)

2021 ◽  
Vol 22 (19) ◽  
pp. 10594
Author(s):  
Aira Sarkar ◽  
Vijayabhaskarreddy Junnuthula ◽  
Sathish Dyawanapelly
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Macular Degeneration ◽  
Small Molecules ◽  
Vision Loss ◽  
Age Related Macular Degeneration ◽  
Treatment Modalities ◽  
Inherited Disease ◽  
Therapeutic Benefits ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of vision loss in geriatric population. Intravitreal (IVT) injections are popular clinical option. Biologics and small molecules offer efficacy but relatively shorter half-life after intravitreal injections. To address these challenges, numerous technologies and therapies are under development. Most of these strategies aim to reduce the frequency of injections, thereby increasing patient compliance and reducing patient-associated burden. Unlike IVT frequent injections, molecular therapies such as cell therapy and gene therapy offer restoration ability hence gained a lot of traction. The recent approval of ocular gene therapy for inherited disease offers new hope in this direction. However, until such breakthrough therapies are available to the majority of patients, antibody therapeutics will be on the shelf, continuing to provide therapeutic benefits. The present review aims to highlight the status of pre-clinical and clinical studies of neovascular AMD treatment modalities including Anti-VEGF therapy, upcoming bispecific antibodies, small molecules, port delivery systems, photodynamic therapy, radiation therapy, gene therapy, cell therapy, and combination therapies.

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.

Nanotherapies for the Treatment of Age-Related Macular Degeneration (AMD) Disease: Recent Advancements and Challenges

2020 ◽  
Vol 13 (4) ◽  
pp. 283-290 ◽  
Author(s):  
Vamshi Krishna Rapalli ◽  
Srividya Gorantla ◽  
Tejashree Waghule ◽  
Arisha Mahmood ◽  
Prem Prakash Singh ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Targeted Delivery ◽  
Large Population ◽  
Posterior Part ◽  
Therapeutic Agents ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Disease Site ◽  
Therapeutic Molecules ◽  
Invasive Techniques

Age-related Macular Degeneration (AMD) is one of the common diseases affecting the posterior part of the eye, of a large population above 45 years old. Anti-Vascular Endothelial Growth Factor- A (Anti-VEGF-A) agents have been considered and approved as therapeutic agents for the treatment of AMD. Due to the large molecular weight and poor permeability through various eye membranes, VEGF-A inhibitors are given through an intravitreal injection, even though the delivery of small therapeutic molecules by topical application to the posterior part of the eye exhibits challenges in the treatment. To overcome these limitations, nanocarrier based delivery systems have been utilized to a large extent for the delivery of therapeutics. Nanocarriers system offers prodigious benefits for the delivery of therapeutics to the posterior part of the eye in both invasive and non-invasive techniques. The nano size can improve the permeation of therapeutic agent across the biological membranes. They provide protection from enzymes present at the site, targeted delivery or binding with the disease site and extend the release of therapeutic agents with prolonged retention. This leads to improved therapeutic efficacy, patient compliance, and cost effectiveness of therapy with minimum dose associated side-effects. This review has summarized various nanocarriers explored for the treatment of AMD and challenges in translation.

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.

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