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

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.

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.

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 Emerging Nano-Formulations and Nanomedicines Applications for Ocular Drug Delivery

Nanomaterials ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 173
Author(s):  
Dawin Khiev ◽  
Zeinab A. Mohamed ◽  
Riddhi Vichare ◽  
Ryan Paulson ◽  
Sofia Bhatia ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Inorganic Nanoparticles ◽  
In Vivo Studies ◽  
Ocular Diseases ◽  
Sustained Drug Release ◽  
Blood Retinal Barrier ◽  
Vast Number ◽  
Recent Developments

Ocular diseases can deteriorate vision to the point of blindness and thus can have a major impact on the daily life of an individual. Conventional therapies are unable to provide absolute therapy for all ocular diseases due to the several limitations during drug delivery across the blood-retinal barrier, making it a major clinical challenge. With recent developments, the vast number of publications undergird the need for nanotechnology-based drug delivery systems in treating ocular diseases. The tool of nanotechnology provides several essential advantages, including sustained drug release and specific tissue targeting. Additionally, comprehensive in vitro and in vivo studies have suggested a better uptake of nanoparticles across ocular barriers. Nanoparticles can overcome the blood-retinal barrier and consequently increase ocular penetration and improve the bioavailability of the drug. In this review, we aim to summarize the development of organic and inorganic nanoparticles for ophthalmic applications. We highlight the potential nanoformulations in clinical trials as well as the products that have become a commercial reality.

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

Pharmaceutics ◽  
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.

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.

scholarly journals Drusen in patient-derived hiPSC-RPE models of macular dystrophies

2017 ◽  
Vol 114 (39) ◽  
pp. E8214-E8223 ◽  
Author(s):  
Chad A. Galloway ◽  
Sonal Dalvi ◽  
Sandy S. C. Hung ◽  
Leslie A. MacDonald ◽  
Lisa R. Latchney ◽  
...  
Keyword(s):  
Vision Loss ◽  
Retinal Pigment ◽  
Retinal Dystrophy ◽  
Age Related Macular Degeneration ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Rpe Cells ◽  
Age Related ◽  
Pathway Gene ◽  
Human Pathology

Age-related macular degeneration (AMD) and related macular dystrophies (MDs) are a major cause of vision loss. However, the mechanisms underlying their progression remain ill-defined. This is partly due to the lack of disease models recapitulating the human pathology. Furthermore, in vivo studies have yielded limited understanding of the role of specific cell types in the eye vs. systemic influences (e.g., serum) on the disease pathology. Here, we use human induced pluripotent stem cell-retinal pigment epithelium (hiPSC-RPE) derived from patients with three dominant MDs, Sorsby’s fundus dystrophy (SFD), Doyne honeycomb retinal dystrophy/malattia Leventinese (DHRD), and autosomal dominant radial drusen (ADRD), and demonstrate that dysfunction of RPE cells alone is sufficient for the initiation of sub-RPE lipoproteinaceous deposit (drusen) formation and extracellular matrix (ECM) alteration in these diseases. Consistent with clinical studies, sub-RPE basal deposits were present beneath both control (unaffected) and patient hiPSC-RPE cells. Importantly basal deposits in patient hiPSC-RPE cultures were more abundant and displayed a lipid- and protein-rich “drusen-like” composition. Furthermore, increased accumulation of COL4 was observed in ECM isolated from control vs. patient hiPSC-RPE cultures. Interestingly, RPE-specific up-regulation in the expression of several complement genes was also seen in patient hiPSC-RPE cultures of all three MDs (SFD, DHRD, and ADRD). Finally, although serum exposure was not necessary for drusen formation, COL4 accumulation in ECM, and complement pathway gene alteration, it impacted the composition of drusen-like deposits in patient hiPSC-RPE cultures. Together, the drusen model(s) of MDs described here provide fundamental insights into the unique biology of maculopathies affecting the RPE–ECM interface.

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