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Ocular Drug Delivery: Present Innovations and Future Challenges

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 64847

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Prof. Dr. María Ángeles Solinís

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Nanotechnology and Gene Therapy Group (PharmaNanoGene), Campus Alava, Universidad del Pais Vasco—Euskal Herriko Unibertsitatea, Vitoria-Gasteiz, Spain
Interests: gene therapy; controlled drug delivery; retinal gene therapy; nonviral vectors; lipid nanoparticles; ocular drug delivery; bioavailability; pharmacokinetics; formulations; nanoparticles drug delivery; pharmacology; nanomedicine; nanotechnology; bioequivalence studies; messenger RNA; therapeutic nucleic acids; lysosomal storage diseases
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Prof. Dr. Ana Del Pozo-Rodríguez

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Guest Editor

Nanotechnology and Gene Therapy Group (PharmaNanoGene), Campus Alava, Universidad del Pais Vasco—Euskal Herriko Unibertsitatea, Vitoria-Gasteiz, Spain
Interests: pharmaceutics and pharmaceutical technology; controlled drug delivery; drug formulation development; nanotechnology in drug delivery; pharmaceutical research and development; ocular drug delivery; novel drug delivery systems; gene therapy; retinal gene therapy; nonviral vectors; lipid nanoparticles; messenger RNA; therapeutic nucleic acids; lysosomal storage diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The eye has been largely at the forefront of translational therapy due to appropriate disease targets and its suitable anatomic features. However, the eye possesses very limiting barriers to the accessibility of drugs, and the design of effective delivery systems to the anterior and, more particularly, the posterior segment of the eye is a challenging issue for the pharmaceutical scientists.

The increasing demand for effective and, ideally, non-invasive drug delivery methods is especially important in the case of ocular administration, to overcome bioavailability hurdles and provide effective concentrations of drug at the target cells or tissues, for a suitable period of time. In addition, ocular delivery systems have to face new therapeutic approaches including the administration of biological entities, such us monoclonal antibodies, peptides, proteins, cellular therapies or nucleic acids.

This Special Issue attempts to highlight the current state and future perspectives in the research area of ocular drug delivery systems. It will be focused on innovative devices for topical and intraocular drug administration, in vivo, ex vivo and in vitro 3D models, and the challenges and opportunities for implementation of advanced therapy medicinal products that comprise cell therapies, gene therapeutics, and tissue engineered products.

Prof. Dr. María Ángeles Solinís
Prof. Dr. Ana Del Pozo-Rodríguez
Guest Editors

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Keywords

ocular drug delivery
intraocular administration
topical administration
ocular devices
nanotechnology
gene therapy
gene editing
manufacturing and quality control
tissue engineering
in vitro 3D models

Related Special Issue

Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II) in Pharmaceutics (7 articles)

Published Papers (12 papers)

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Research

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19 pages, 17043 KiB

Open AccessArticle

An Injectable Nano-Enabled Thermogel to Attain Controlled Delivery of p11 Peptide for the Potential Treatment of Ocular Angiogenic Disorders of the Posterior Segment

by Lisa Claire du Toit, Yahya Essop Choonara and Viness Pillay

Pharmaceutics 2021, 13(2), 176; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020176 - 28 Jan 2021

Cited by 11 | Viewed by 2721

Abstract

This investigation focused on the design of an injectable nano-enabled thermogel (nano-thermogel) system to attain controlled delivery of p11 anti-angiogenic peptide for proposed effective prevention of neovascularisation and to overcome the drawbacks of the existing treatment approaches for ocular disorders characterised by angiogenesis, which employ multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) antibodies. Synthesis of a polyethylene glycol-polycaprolactone-polyethylene glycol (PEG-PCL-PEG) triblock co-polymer was undertaken, followed by characterisation employing Fourier-transform infrared (FTIR) spectroscopy, nuclear magnetic resonance (NMR) spectroscopy and differential scanning calorimetry (DSC) to ascertain the chemical stability and integrity of the co-polymer instituted for nano-thermogel formulation. The p11 anti-angiogenic peptide underwent encapsulation within poly(lactic-co-glycolic acid) (PLGA) nanoparticles via a double emulsion solvent evaporation method and was incorporated into the thermogel following characterisation by scanning electron microscopy (SEM), zeta size and zeta-potential analysis. The tube inversion approach and rheological analysis were employed to ascertain the thermo-sensitive sol-gel conversion of the nano-thermogel system. Chromatographic assessment of the in vitro release of the peptide was performed, with stability confirmation via Tris-Tricine PAGE (Polyacrylamide Gel Electrophoresis). In vitro biocompatibility of the nano-thermogel system was investigated employing a retinal cell line (ARP-19). A nanoparticle size range of 100–200 nm and peptide loading efficiency of 67% was achieved. Sol-gel conversion of the nano-thermogel was observed between 32–45 °C. Release of the peptide in vitro was sustained, with maintenance of stability, for 60 days. Biocompatibility assessment highlighted 97–99% cell viability with non-haemolytic ability, which supports the potential applicability of the nano-thermogel system for extended delivery of peptide for ocular disorder treatment. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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15 pages, 2388 KiB

Open AccessArticle

Inhibition of MicroRNA 6937 Delays Photoreceptor and Vision Loss in a Mouse Model of Retinitis Pigmentosa

by Ander Anasagasti, Araceli Lara-López, Santiago Milla-Navarro, Leire Escudero-Arrarás, María Rodríguez-Hidalgo, Nerea Zabaleta, Gloria González Aseguinolaza, Pedro de la Villa and Javier Ruiz-Ederra

Pharmaceutics 2020, 12(10), 913; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12100913 - 24 Sep 2020

Cited by 8 | Viewed by 2636

Abstract

Inherited retinal dystrophies (IRDs) are a group of rare retinal conditions, including retinitis pigmentosa (RP), caused by monogenic mutations in 1 out of more than 250 genes. Despite recent advancements in gene therapy, there is still a lack of an effective treatment for this group of retinal conditions. MicroRNAs (miRNAs) are a class of highly conserved small non-coding RNAs that inhibit gene expression. Control of miRNAs-mediated protein expression has been described as a widely used mechanism for post-transcriptional regulation in many physiological and pathological processes in different organs, including the retina. Our main purpose was to test the hypothesis that modulation of a group of miRNAs can protect photoreceptor cells from death in the rd10 mouse model of retinitis pigmentosa. For this, we incorporated modulators of three miRNAs in adeno-associated viruses (AAVs), which were administered through sub-retinal injections. The results obtained indicate that inhibition of the miR-6937-5p slows down the visual deterioration of rd10 mice, reflected by an increased electroretinogram (ERG) wave response under scotopic conditions and significant preservation of the outer nuclear layer thickness. This work contributes to broadening our knowledge on the molecular mechanisms underlying retinitis pigmentosa and supports the development of novel therapeutic approaches for RP based on miRNA modulation. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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23 pages, 6238 KiB

Open AccessArticle

Topical Administration of SLN-Based Gene Therapy for the Treatment of Corneal Inflammation by De Novo IL-10 Production

by Mónica Vicente-Pascual, Itziar Gómez-Aguado, Julen Rodríguez-Castejón, Alicia Rodríguez-Gascón, Elisabetta Muntoni, Luigi Battaglia, Ana del Pozo-Rodríguez and María Ángeles Solinís Aspiazu

Pharmaceutics 2020, 12(6), 584; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12060584 - 23 Jun 2020

Cited by 15 | Viewed by 3658

Abstract

One of the main challenges in gene therapy is the issue of delivery, and it is especially relevant for the success of gene therapy in the cornea. In the present work, eye drops containing biocompatible non-viral vectors based on solid lipid nanoparticles (SLNs) as gene delivery systems to induce the expression of interleukin 10 (IL-10) were designed to address the treatment of corneal inflammation. Two kinds of SLNs combined with different ligands (protamine, dextran, or hyaluronic acid (HA)) and formulated with polyvinyl alcohol (PVA) were prepared. SLN-based vectors were characterized in terms of size, adhesiveness, viscosity, and pH, before topical administration to wild type and IL-10 knock out (KO) mice. The formulations showed a homogenous particle size below 400 nm and a positive surface charge to favor bioadhesion; the incorporation of PVA improved the corneal penetration. After three days of treatment by topical instillation, SLN-based vectors mainly transfected corneal epithelial cells, HA-formulations being the most effective ones. IL-10 was capable of reaching even the endothelial layer. Corneal sections showed no histological change and formulations seemed to be well tolerated after repeated topical administration. These promising results highlight the possible contribution of non-viral gene augmentation therapy to the future clinical approach of corneal gene therapy. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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19 pages, 1258 KiB

Open AccessArticle

Ciprofloxacin Loaded Nanostructured Lipid Carriers Incorporated into In-Situ Gels to Improve Management of Bacterial Endophthalmitis

by Ahmed Youssef, Narendar Dudhipala and Soumyajit Majumdar

Pharmaceutics 2020, 12(6), 572; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12060572 - 19 Jun 2020

Cited by 67 | Viewed by 5189

Abstract

Bacterial endophthalmitis (BE) is a potentially sight-threatening inflammatory reaction of the intraocular fluids or tissues caused by bacteria. Ciprofloxacin (CIP) eye drops are prescribed as first-line therapy in BE. However, frequent administration is necessary due to precorneal loss and poor ocular bioavailability. The objective of the current research was to prepare CIP containing nanostructured lipid carriers (CIP-NLCs) loaded an in situ gel system (CIP-NLC-IG) for topical ocular administration for enhanced and sustained antibacterial activity in BE treatment. CIP-NLCs were prepared by the hot homogenization method and optimized based on physicochemical characteristics and physical stability. The optimized CIP-NLC formulation was converted into CIP-NLC-IG with the addition of gellan gum as a gelling agent. Furthermore, optimized CIP-NLC and CIP-NLC-IG were evaluated for in vitro release and ex vivo transcorneal permeation studies, using commercial CIP ophthalmic solution (CIP-C) as the control. The optimized CIP-NLC formulation showed particle size, polydispersity index, zeta potential, assay and entrapment efficiency of 193.1 ± 5.1 nm, 0.43 ± 0.01, −32.5 ± 1.5 mV, 99.5 ± 5.5 and 96.3 ± 2.5%, respectively. CIP-NLC-IG with 0.2% w/v gellan gum showed optimal viscoelastic characteristics. The in vitro release studies demonstrated sustained release of CIP from CIP-NLC and CIP-NLC-IG formulations over a 24 h period. Transcorneal flux and permeability increased 4 and 3.5-fold, and 2.2 and 1.9-fold from CIP-NLC and CIP-NLC-IG formulations, respectively, when compared to CIP-C. The results demonstrate that CIP-NLC-IG could be considered as an alternate delivery system to prolong the residence time on the ocular surface after topical administration. Thus, the current CIP ophthalmic formulations may exhibit improved ocular bioavailability and prolonged antibacterial activity, which may improve therapeutic outcomes in the treatment of BE. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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13 pages, 451 KiB

Open AccessArticle

Microscale Thermophoresis as a Screening Tool to Predict Melanin Binding of Drugs

by Laura Hellinen, Sina Bahrpeyma, Anna-Kaisa Rimpelä, Marja Hagström, Mika Reinisalo and Arto Urtti

Pharmaceutics 2020, 12(6), 554; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12060554 - 16 Jun 2020

Cited by 17 | Viewed by 3782

Abstract

Interactions between drugs and melanin pigment may have major impacts on pharmacokinetics. Therefore, melanin binding can modify the efficacy and toxicity of medications in ophthalmic and other disease of pigmented tissues, such as melanoma. As melanin is present in many pigmented tissues in the human body, investigation of pigment binding is relevant in drug discovery and development. Conventionally, melanin binding assays have been performed using an equilibrium binding study followed by chemical analytics, such as LC/MS. This approach is laborious, relatively slow, and limited to facilities with high performance quantitation instrumentation. We present here a screening of melanin binding with label-free microscale thermophoresis (MST) that utilizes the natural autofluorescence of melanin. We determined equilibrium dissociation constants (K_d) of 11 model compounds with melanin nanoparticles. MST categorized the compounds into extreme (chloroquine, penicillin G), high (papaverine, levofloxacin, terazosin), intermediate (timolol, nadolol, quinidine, propranolol), and low melanin binders (atropine, methotrexate, diclofenac) and displayed good correlation with binding parameter values obtained with the conventional binding study and LC/MS analytics. Further, correlation was seen between predicted melanin binding in human retinal pigment epithelium and choroid (RPE-choroid) and K_d values obtained with MST. This method represents a useful and fast approach for classification of compounds regarding melanin binding. Thus, the method can be utilized in various fields, including drug discovery, pharmacokinetics, and toxicology. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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18 pages, 2287 KiB

Open AccessArticle

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents

by Sergio Esteban-Pérez, Vanessa Andrés-Guerrero, José Javier López-Cano, Irene Molina-Martínez, Rocio Herrero-Vanrell and Irene Bravo-Osuna

Pharmaceutics 2020, 12(4), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12040306 - 28 Mar 2020

Cited by 23 | Viewed by 3715

Abstract

The increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients. In the present work, we have explored the potential of gelatin nanoparticles (GNPs) loaded with timolol maleate (TM), a beta-adrenergic blocker widely used in the clinic for glaucoma treatment and a hybrid system of TM-GNPs included in a hydroxypropyl methylcellulose (HPMC) viscous solution. The TM- loaded nanoparticles (mean particle size of 193 ± 20 nm and drug loading of 0.291 ± 0.019 mg TM/mg GNPs) were well tolerated both in vitro (human corneal cells) and in vivo. The in vivo efficacy studies performed in normotensive rabbits demonstrated that these gelatin nanoparticles were able to achieve the same hypotensive effect as a marketed formulation (0.5% TM) containing a 5-fold lower concentration of the drug. When comparing commercial and TM-GNPs formulations with the same TM dose, nanoparticles generated an increased efficacy with a significant (p < 0.05) reduction of intraocular pressure (IOP) (from 21% to 30%) and an augmentation of 1.7-fold in the area under the curve (AUC)_(0–12h). On the other hand, the combination of timolol-loaded nanoparticles (TM 0.1%) and the viscous polymer HPMC 0.3%, statistically improved the IOP reduction up to 30% (4.65 mmHg) accompanied by a faster time of maximum effect (t_max = 1 h). Furthermore, the hypotensive effect was extended for four additional hours, reaching a pharmacological activity that lasted 12 h after a single instillation of this combination, and leading to an AUC_(0–12h) 2.5-fold higher than the one observed for the marketed formulation. According to the data presented in this work, the use of hybrid systems that combine well tolerated gelatin nanoparticles and a viscous agent could be a promising alternative in the management of high intraocular pressure in glaucoma. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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17 pages, 5202 KiB

Open AccessArticle

Development of Kaempferol-Loaded Gelatin Nanoparticles for the Treatment of Corneal Neovascularization in Mice

by Yu-Lun Chuang, Hsu-Wei Fang, Aditya Ajitsaria, Ko-Hua Chen, Chen-Ying Su, Guei-Sheung Liu and Ching-Li Tseng

Pharmaceutics 2019, 11(12), 635; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics11120635 - 28 Nov 2019

Cited by 37 | Viewed by 5207

Abstract

Cornea is the transparent layer in front of the eye that does not contain blood vessels. Among eye diseases, corneal neovascularization (NV) is one of the major causes of vision loss, since it can also lead to blindness. An herbal extraction containing flavonoid, kaempferol (KA), with antiangiogenic effect was chosen as a candidate drug for inhibited vessel formation. The use of nanomedicine has led to higher drug bioavailability and slow release of the drug as an effective therapeutic formulation in ocular drug delivery. In this study, we prepared gelatin nanoparticles (GNP) with kaempferol encapsulation (GNP-KA) for corneal NV treatment by topical delivery, i.e., eye drops. We found that GNP with/without KA loading was in the size of 85−150 nm, and its zeta potential was around 22−26 mV. The KA entrapment rate of GNP-KA was around 90−98%, and the loading rate was about 4.6%. The TEM results clearly indicated the GNP-KA NPs to be round spheres. The in vitro test involved the adoption of human umbilical vein endothelial cells (HUVECs) for coculture with these nanoparticles. From WST-8 assay, and cell migration examinations, it was evident that GNP-KA had the capacity to inhibit the cell viability and function of HUVECs. The results from in vivo tests such as ocular vessels observation, hematoxylin & eosin (H&E) stain, and metalloproteinases (MMP)/vascular endothelial growth factor (VEGF) quantification revealed the mice’s eyes with corneal NV treated by eye drops containing GNP-KA once daily for 7 days had better therapeutic effects with less vessels in-growths in the cornea, compared to the KA solution group by reducing the production of MMP and VEGF in the cornea. Therefore, we expected to achieve a comfortable treatment with a simple method using nanomedicine (GNP-KA) as ophthalmological agent delivered as eye drops. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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Review

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32 pages, 1545 KiB

Open AccessReview

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

by Hyeong Min Kim and Se Joon Woo

Pharmaceutics 2021, 13(1), 108; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010108 - 15 Jan 2021

Cited by 96 | Viewed by 12745

Abstract

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. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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38 pages, 2425 KiB

Open AccessReview

Advancement on Sustained Antiviral Ocular Drug Delivery for Herpes Simplex Virus Keratitis: Recent Update on Potential Investigation

by Manisha Pandey, Hira Choudhury, Azila Abdul-Aziz, Subrat Kumar Bhattamisra, Bapi Gorain, Jocelyn Sziou Ting Su, Choo Leey Tan, Woon Yee Chin and Khar Yee Yip

Pharmaceutics 2021, 13(1), 1; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010001 - 22 Dec 2020

Cited by 22 | Viewed by 5554

Abstract

The eyes are the window to the world and the key to communication, but they are vulnerable to multitudes of ailments. More serious than is thought, corneal infection by herpes simplex viruses (HSVs) is a prevalent yet silent cause of blindness in both the paediatric and adult population, especially if immunodeficient. Globally, there are 1.5 million new cases and forty thousand visual impairment cases reported yearly. The Herpetic Eye Disease Study recommends topical antiviral as the front-line therapy for HSV keratitis. Ironically, topical eye solutions undergo rapid nasolacrimal clearance, which necessitates oral drugs but there is a catch of systemic toxicity. The hurdle of antiviral penetration to reach an effective concentration is further complicated by drugs’ poor permeability and complex layers of ocular barriers. In this current review, novel delivery approaches for ocular herpetic infection, including nanocarriers, prodrugs, and peptides are widely investigated, with special focus on advantages, challenges, and recent updates on in situ gelling systems of ocular HSV infections. In general congruence, the novel drug delivery systems play a vital role in prolonging the ocular drug residence time to achieve controlled release of therapeutic agents at the application site, thus allowing superior ocular bioavailability yet fewer systemic side effects. Moreover, in situ gel functions synergistically with nanocarriers, prodrugs, and peptides. The findings support that novel drug delivery systems have potential in ophthalmic drug delivery of antiviral agents, and improve patient convenience when prolonged and chronic topical ocular deliveries are intended. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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31 pages, 5182 KiB

Open AccessReview

Three-Dimensional Human Cell Culture Models to Study the Pathophysiology of the Anterior Eye

by Laura García-Posadas and Yolanda Diebold

Pharmaceutics 2020, 12(12), 1215; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12121215 - 15 Dec 2020

Cited by 8 | Viewed by 3336

Abstract

In recent decades, the establishment of complex three-dimensional (3D) models of tissues has allowed researchers to perform high-quality studies and to not only advance knowledge of the physiology of these tissues but also mimic pathological conditions to test novel therapeutic strategies. The main advantage of 3D models is that they recapitulate the spatial architecture of tissues and thereby provide more physiologically relevant information. The eye is an extremely complex organ that comprises a large variety of highly heterogeneous tissues that are divided into two asymmetrical portions: the anterior and posterior segments. The anterior segment consists of the cornea, conjunctiva, iris, ciliary body, sclera, aqueous humor, and the lens. Different diseases in these tissues can have devastating effects. To study these pathologies and develop new treatments, the use of cell culture models is instrumental, and the better the model, the more relevant the results. Thus, the development of sophisticated 3D models of ocular tissues is a significant challenge with enormous potential. In this review, we present a comprehensive overview of the latest advances in the development of 3D in vitro models of the anterior segment of the eye, with a special focus on those that use human primary cells. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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25 pages, 1075 KiB

Open AccessReview

Adeno-Associated Virus Mediated Gene Therapy for Corneal Diseases

by Prabhakar Bastola, Liujiang Song, Brian C. Gilger and Matthew L. Hirsch

Pharmaceutics 2020, 12(8), 767; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12080767 - 13 Aug 2020

Cited by 21 | Viewed by 5421

Abstract

According to the World Health Organization, corneal diseases are the fourth leading cause of blindness worldwide accounting for 5.1% of all ocular deficiencies. Current therapies for corneal diseases, which include eye drops, oral medications, corrective surgeries, and corneal transplantation are largely inadequate, have undesirable side effects including blindness, and can require life-long applications. Adeno-associated virus (AAV) mediated gene therapy is an optimistic strategy that involves the delivery of genetic material to target human diseases through gene augmentation, gene deletion, and/or gene editing. With two therapies already approved by the United States Food and Drug Administration and 200 ongoing clinical trials, recombinant AAV (rAAV) has emerged as the in vivo viral vector-of-choice to deliver genetic material to target human diseases. Likewise, the relative ease of applications through targeted delivery and its compartmental nature makes the cornea an enticing tissue for AAV mediated gene therapy applications. This current review seeks to summarize the development of AAV gene therapy, highlight preclinical efficacy studies, and discuss potential applications and challenges of this technology for targeting corneal diseases. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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30 pages, 1097 KiB

Open AccessReview

Polysaccharides in Ocular Drug Delivery

by Natallia Dubashynskaya, Daria Poshina, Sergei Raik, Arto Urtti and Yury A. Skorik

Pharmaceutics 2020, 12(1), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12010022 - 24 Dec 2019

Cited by 99 | Viewed by 9303

Abstract

Polysaccharides, such as cellulose, hyaluronic acid, alginic acid, and chitosan, as well as polysaccharide derivatives, have been successfully used to augment drug delivery in the treatment of ocular pathologies. The properties of polysaccharides can be extensively modified to optimize ocular drug formulations and to obtain biocompatible and biodegradable drugs with improved bioavailability and tailored pharmacological effects. This review discusses the available polysaccharide choices for overcoming the difficulties associated with ocular drug delivery, and it explores the reasons for the dependence between the physicochemical properties of polysaccharide-based drug carriers and their efficiency in different formulations and applications. Polysaccharides will continue to be of great interest to researchers endeavoring to develop ophthalmic drugs with improved effectiveness and safety. Full article

(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges)

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