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Pharmaceuticals
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Recent Advances in Ocular Drug Delivery Systems
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Recent Advances in Ocular Drug Delivery Systems

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (15 December 2023) | Viewed by 22202

Special Issue Editors

Dr. Sibel Cetinel

E-Mail Website
Guest Editor
Sabanci University Nanotechnology Research and Application Center, SUNUM, Tuzla, Istanbul 34956, Turkey
Interests: nanomedicine; tissue engineering; ocular drug delivery; cataract; glaucoma; AMD
Dr. Ali Zarrabi

E-Mail Website
Guest Editor
Biomedical Engineering Department, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Turkey
Interests: nanomedicine; theranpstics; diagnosis; therapy; drug delivery systems; cancer; neurodegenerative disease; miRNA; siRNA; wound healing; biomedical engineering; biomaterials
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nowadays, not only the aged population but also younger people are suffering from ocular diseases. Modern lifestyles are assumed to be the main causes of these diseases, which include macular degeneration, cataracts, diabetic retinopathy, glaucoma, dry eye syndrome, inflammation, and ocular allergies. While therapeutic agents are currently available for treating most of these diseases, new medicines or drug delivery systems are expected to improve clinical outcomes and combat such diseases. The main obstacles in evolving therapeutic formulations for treating diseases of different parts of the eye are dispatching the effective drug concentration to the target site in a sustained manner, while minimizing side effects and enhancing patient compliance. The unique anatomy and physiology of the eye make this challenging, and treatments require advanced developments in the field of minimally or noninvasive ocular drug delivery systems.

This Special Issue, entitled “Ocular Drug Delivery Systems”, aims to cover advanced developments in the field of drug delivery systems for the eye. The scope of these papers spans from applications of emerging/advanced materials in the prevention, diagnosis, and treatment of eye diseases to translation medicine and clinical trials. Submissions of original research work and review manuscripts are welcome.

We invite high-quality papers that are based around the following keywords:

  • Eye/ocular drug delivery systems;
  • Ocular nanomedicine;
  • Ocular diagnosis and theragnostics;
  • Ocular gene therapy;
  • Blood–aqueous barrier;
  • Blood–retina barrier;
  • Minimally or noninvasive methods;
  • nAMD;
  • Glaucoma;
  • Retinopathy;
  • Dry eye syndrome.

Dr. Sibel Cetinel
Dr. Ali Zarrabi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • eye/ocular drug delivery systems
  • ocular nanomedicine
  • ocular diagnosis and theragnostics
  • ocular gene therapy
  • blood–aqueous barrier
  • blood–retina barrier
  • minimally or noninvasive methods
  • nAMD
  • glaucoma
  • retinopathy
  • dry eye syndrome

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Published Papers (6 papers)

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Research

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14 pages, 7751 KiB  
Article
Microscopic and Biopharmaceutical Evaluation of Emulsion and Self-Emulsifying Oil with Cyclosporine
by Eliza Wolska, Małgorzata Sznitowska, Juliusz Chorążewicz, Katarzyna Krzemińska, Oliwia Szerkus, Aleksandra Radwańska, Michał J. Markuszewski, Roman Kaliszan and Krystyna Raczyńska
Pharmaceuticals 2023, 16(12), 1713; https://doi.org/10.3390/ph16121713 - 11 Dec 2023
Cited by 2 | Viewed by 1905
Abstract
Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research [...] Read more.
Among the currently available commercial eye drops with cyclosporine A (Cs) there is a lack of long-acting dosage forms and products with a concentration of the drug substance higher than 0.1%, although Cs is widely used in ophthalmology. The aim of the research was to conduct the microscopic and biopharmaceutical evaluation of two formulations, an emulsion (EM) and a self-emulsifying oil (SEO), both with 0.5% of Cs, proposed for use in eye drops, and the comparison of both. SEO eye drops with Cs or any other drug substance are currently not available as marketed products, and the highest concentration of Cs in the ocular emulsion is only 0.1%. The microscopic evaluation of the emulsion and the SEO after emulsification with water was carried out using a high-resolution digital microscopy. The properties of both preparations were compared using the high dynamic range function or optical shadow effect mode. Images in the 3D composition mode were also recorded. The in vivo study of the Cs formulations was performed on male albino rabbits. The eye tolerance of the preparations was assessed using the ocular irritation test, which is a modified Draize test. Placebo carriers (without the drug substance) were also subjected to irritation testing. The concentration of Cs in the tissues (cornea and conjunctiva) and fluids (tear fluid and aqueous humor) of the rabbit eye was determined after multiple instillations of Cs–EM or Cs–SEO. The tested preparations were compared using the digital microscopy technique, which highlights the features of the formulations and eliminates the risk of unnoticeable properties that are difficult to observe in classical optical microscopy. Both tested Cs-loaded formulations are classified as practically non-irritating. There were also no significant differences when testing the placebo carriers. After a topical administration, Cs was widely distributed in all tissues (e.g., in cornea 1.3 ng/mg and 1.0 ng/mg) and fluids of the eye (e.g., in tear fluid 11.6 µg/mL and 4.3 µg/mL), after the administration of Cs–SEO and Cs–EM, respectively. The obtained results allow us to recognize both tested formulations, the emulsion and the self-emulsifying oil with 0.5% Cs content, as carriers safe for ophthalmic use and effective in delivering the drug substance to the structures of the eye. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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18 pages, 1302 KiB  
Article
Binary Polymeric Surfactant Mixtures for the Development of Novel Loteprednol Etabonate Nanomicellar Eyedrops
by Silvia Tampucci, Daniela Monti, Susi Burgalassi, Eleonora Terreni, Valentina Paganini, Mariacristina Di Gangi and Patrizia Chetoni
Pharmaceuticals 2023, 16(6), 864; https://doi.org/10.3390/ph16060864 - 10 Jun 2023
Cited by 5 | Viewed by 2118
Abstract
The treatment of several ocular inflammatory conditions affecting different areas of the ocular globe involves the administration of topical ophthalmic formulations containing corticosteroids. This research was aimed at evaluating the solubilising efficacy of 5.0% w/w of different binary mixtures of commercial [...] Read more.
The treatment of several ocular inflammatory conditions affecting different areas of the ocular globe involves the administration of topical ophthalmic formulations containing corticosteroids. This research was aimed at evaluating the solubilising efficacy of 5.0% w/w of different binary mixtures of commercial amphiphilic polymeric surfactants with the purpose of obtaining nanomicellar solutions containing a high amount of loteprednol etabonate (LE). The selected LE-TPGS/HS nanomicelles, containing 0.253 mg/mL of the drug, had a small size (=13.57 nm) and uniform distribution (Polydispersity Index = 0.271), appeared completely transparent and perfectly filterable through 0.2 μm membrane filter, and remained stable up to 30 days at 4 °C. The critical micellar concentration (CMCTPGS/HS) was 0.0983 mM and the negative value of the interaction parameter between the polymeric-surfactant-building unit (βTPGS/HS = −0.1322) confirmed the ability of the polymeric surfactants to interact, favouring the dissolution of LE into nanomicelles. The disappearance of the endothermic peak of LE in the DSC analysis confirmed the interactions of LE with the polymeric surfactants. LE-TPGS/HS produced in vitro LE which sustained diffusion for 44 h (more than 40% of encapsulated LE). Furthermore, the lack of a significant cytotoxic effect on a sensitive corneal epithelial cell line makes it a candidate for further biological studies. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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Review

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35 pages, 3821 KiB  
Review
What’s New in Ocular Drug Delivery: Advances in Suprachoroidal Injection since 2023
by Kevin Y. Wu, Angel Gao, Michel Giunta and Simon D. Tran
Pharmaceuticals 2024, 17(8), 1007; https://doi.org/10.3390/ph17081007 - 30 Jul 2024
Cited by 2 | Viewed by 4078
Abstract
Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing [...] Read more.
Despite significant advancements in ocular drug delivery, challenges persist in treating posterior segment diseases like macular edema (ME) and age-related macular degeneration (AMD). Suprachoroidal (SC) injections are a promising new method for targeted drug delivery to the posterior segment of the eye, providing direct access to the choroid and retina while minimizing systemic exposure and side effects. This review examines the anatomical and physiological foundations of the SC space; evaluates delivery devices such as microcatheters, hypodermic needles, and microneedles; and discusses pharmacokinetic principles. Additionally, advancements in gene delivery through SC injections are explored, emphasizing their potential to transform ocular disease management. This review also highlights clinical applications in treating macular edema, diabetic macular edema, age-related macular degeneration, choroidal melanoma, and glaucoma. Overall, SC injections are emerging as a promising novel route for administering ophthalmic treatments, with high bioavailability, reduced systemic exposure, and favorable safety profiles. Key therapeutic agents such as triamcinolone acetonide, dexamethasone, AAV-based gene therapy, and axitinib have shown promise. The field of suprachoroidal injection is progressing rapidly, and this review article, while attempting to encapsulate most of the published preclinical and clinical studies, mainly focuses on those that are published within 2023 and 2024. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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17 pages, 3326 KiB  
Review
Advanced Therapy Medicinal Products for Age-Related Macular Degeneration; Scaffold Fabrication and Delivery Methods
by Hanieh Khalili, Hamid Heidari Kashkoli, David Edward Weyland, Sama Pirkalkhoran and Wiktoria Roksana Grabowska
Pharmaceuticals 2023, 16(4), 620; https://doi.org/10.3390/ph16040620 - 20 Apr 2023
Cited by 5 | Viewed by 4677
Abstract
Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal [...] Read more.
Retinal degenerative diseases such as age-related macular degeneration (AMD) represent a leading cause of blindness, resulting in permanent damage to retinal cells that are essential for maintaining normal vision. Around 12% of people over the age of 65 have some form of retinal degenerative disease. Whilst antibody-based drugs have revolutionised treatment of neovascular AMD, they are only effective at an early stage and cannot prevent eventual progression or allow recovery of previously lost vision. Hence, there is a clear unmet need to find innovative treatment strategies to develop a long-term cure. The replacement of damaged retinal cells is thought to be the best therapeutic strategy for the treatment of patients with retinal degeneration. Advanced therapy medicinal products (ATMPs) are a group of innovative and complex biological products including cell therapy medicinal products, gene therapy medicinal products, and tissue engineered products. Development of ATMPs for the treatment of retinal degeneration diseases has become a fast-growing field of research because it offers the potential to replace damaged retinal cells for long-term treatment of AMD. While gene therapy has shown encouraging results, its effectiveness for treatment of retinal disease may be hampered by the body’s response and problems associated with inflammation in the eye. In this mini-review, we focus on describing ATMP approaches including cell- and gene-based therapies for treatment of AMD along with their applications. We also aim to provide a brief overview of biological substitutes, also known as scaffolds, that can be used for delivery of cells to the target tissue and describe biomechanical properties required for optimal delivery. We describe different fabrication methods for preparing cell-scaffolds and explain how the use of artificial intelligence (AI) can aid with the process. We predict that combining AI with 3D bioprinting for 3D cell-scaffold fabrication could potentially revolutionise retinal tissue engineering and open up new opportunities for developing innovative platforms to deliver therapeutic agents to the target tissues. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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32 pages, 3958 KiB  
Review
Application of Convergent Science and Technology toward Ocular Disease Treatment
by Ayça Bal-Öztürk, Ece Özcan-Bülbül, Hazal Ezgi Gültekin, Berivan Cecen, Ebru Demir, Atefeh Zarepour, Sibel Cetinel and Ali Zarrabi
Pharmaceuticals 2023, 16(3), 445; https://doi.org/10.3390/ph16030445 - 16 Mar 2023
Cited by 5 | Viewed by 4633
Abstract
Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so [...] Read more.
Eyes are one of the main critical organs of the body that provide our brain with the most information about the surrounding environment. Disturbance in the activity of this informational organ, resulting from different ocular diseases, could affect the quality of life, so finding appropriate methods for treating ocular disease has attracted lots of attention. This is especially due to the ineffectiveness of the conventional therapeutic method to deliver drugs into the interior parts of the eye, and the also presence of barriers such as tear film, blood-ocular, and blood-retina barriers. Recently, some novel techniques, such as different types of contact lenses, micro and nanoneedles and in situ gels, have been introduced which can overcome the previously mentioned barriers. These novel techniques could enhance the bioavailability of therapeutic components inside the eyes, deliver them to the posterior side of the eyes, release them in a controlled manner, and reduce the side effects of previous methods (such as eye drops). Accordingly, this review paper aims to summarize some of the evidence on the effectiveness of these new techniques for treating ocular disease, their preclinical and clinical progression, current limitations, and future perspectives. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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17 pages, 2854 KiB  
Review
A Cross Talk between the Endocannabinoid System and Different Systems Involved in the Pathogenesis of Hypertensive Retinopathy
by Farhan Khashim Alswailmi
Pharmaceuticals 2023, 16(3), 345; https://doi.org/10.3390/ph16030345 - 23 Feb 2023
Cited by 3 | Viewed by 3207
Abstract
The prognosis of hypertension leads to organ damage by causing nephropathy, stroke, retinopathy, and cardiomegaly. Retinopathy and blood pressure have been extensively discussed in relation to catecholamines of the autonomic nervous system (ANS) and angiotensin II of the renin–angiotensin aldosterone system (RAAS) but [...] Read more.
The prognosis of hypertension leads to organ damage by causing nephropathy, stroke, retinopathy, and cardiomegaly. Retinopathy and blood pressure have been extensively discussed in relation to catecholamines of the autonomic nervous system (ANS) and angiotensin II of the renin–angiotensin aldosterone system (RAAS) but very little research has been conducted on the role of the ECS in the regulation of retinopathy and blood pressure. The endocannabinoid system (ECS) is a unique system in the body that can be considered as a master regulator of body functions. It encompasses the endogenous production of its cannabinoids, its degrading enzymes, and functional receptors which innervate and perform various functions in different organs of the body. Hypertensive retinopathy pathologies arise normally due to oxidative stress, ischemia, endothelium dysfunction, inflammation, and an activated renin–angiotensin system (RAS) and catecholamine which are vasoconstrictors in their biological nature. The question arises of which system or agent counterbalances the vasoconstrictors effect of noradrenaline and angiotensin II (Ang II) in normal individuals? In this review article, we discuss the role of the ECS and its contribution to the pathogenesis of hypertensive retinopathy. This review article will also examine the involvement of the RAS and the ANS in the pathogenesis of hypertensive retinopathy and the crosstalk between these three systems in hypertensive retinopathy. This review will also explain that the ECS, which is a vasodilator in its action, either independently counteracts the effect produced with the vasoconstriction of the ANS and Ang II or blocks some of the common pathways shared by the ECS, ANS, and Ang II in the regulation of eye functions and blood pressure. This article concludes that persistent control of blood pressure and normal functions of the eye are maintained either by decreasing systemic catecholamine, ang II, or by upregulation of the ECS which results in the regression of retinopathy induced by hypertension. Full article
(This article belongs to the Special Issue Recent Advances in Ocular Drug Delivery Systems)
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