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Pharmaceutics
Special Issues
Recent Advances in Retinal Drug Delivery
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Recent Advances in Retinal Drug Delivery

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 (10 December 2021) | Viewed by 20249

Special Issue Editor

Dr. Ron Neumann

E-Mail Website
Guest Editor
Clinician and consultant on Inflammatory Eye Diseases at Maccabi Health Care Services, Tel Aviv-Yafo, Israel
Interests: retina; drug delivery; anti-VEGF; anti-inflammatory; macular edema; retinal vascular diseases; degenerative diseases

Special Issue Information

Dear Colleagues,

Wise people say that good and bad are interlinked. Each shortcoming on one hand is a blessing on the other. This is nicely presented by the unique situation of the retina regarding drug availability. Being sequestered from the rest of the body in a small eyeball and further isolated via the blood ocular barrier (BOB) makes it difficult for drugs given systemically to cross the vascular network and reach retinal structures. Nonetheless, if a drug is injected into the eyeball, it can easily reach local therapeutic levels and be relatively retained in the eye for a sizable amount of time. Moreover, the systemic dose that reaches the rest of the body following intravitreal injection is minute, and therefore, many adverse events can be bypassed.

This Special Issue will address this unique situation and will encompass topics extending from the trivial question of why repeated injections are not an appropriate solution, to the practicalities of reducing annual injection rates and bypassing injections via other technologies. The field seems to explode with innovative ideas, technologies, and start-up sprouting. Our issue will reflect this and present the reader with a snapshot of today, with a glimpse to the foreseeable future.

Dr. Ron Neumann
Guest Editor

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. Pharmaceutics 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

  • retina
  • drug delivery
  • anti-VEGF
  • anti-inflammatory
  • macular edema
  • retinal vascular diseases
  • degenerative diseases

Published Papers (5 papers)

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Research

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18 pages, 2455 KiB  
Article
Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice
by Daniele Veritti, Valentina Sarao, Gianluca Gorni and Paolo Lanzetta
Pharmaceutics 2022, 14(2), 265; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14020265 - 23 Jan 2022
Cited by 7 | Viewed by 2814
Abstract
Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF. Methods: A time-dependent mathematical model [...] Read more.
Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF. Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization. Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%. Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition. Full article
(This article belongs to the Special Issue Recent Advances in Retinal Drug Delivery)
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Review

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13 pages, 783 KiB  
Review
Retinal Diseases: The Next Frontier in Pharmacodelivery
by Assaf Ben-Arzi, Rita Ehrlich and Ron Neumann
Pharmaceutics 2022, 14(5), 904; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14050904 - 21 Apr 2022
Cited by 7 | Viewed by 3612
Abstract
The future continuous growth of the global older population augments the burden of retinal diseases worldwide. Retinal characteristics isolating and protecting the sensitive neuro-retina from the rest of the ocular tissues challenge drug delivery and promote research and development toward new horizons. In [...] Read more.
The future continuous growth of the global older population augments the burden of retinal diseases worldwide. Retinal characteristics isolating and protecting the sensitive neuro-retina from the rest of the ocular tissues challenge drug delivery and promote research and development toward new horizons. In this review, we wish to describe the unmet medical needs, discuss the novel modes of delivery, and disclose to the reader a spectrum of older-to-novel drug delivery technologies, innovations, and the frontier of pharmacodelivery to the retina. Treating the main retinal diseases in the everlasting war against blindness and its associated morbidity has been growing steadily over the last two decades. Implants, new angiogenesis inhibitor agents, micro- and nano-carriers, and the anchored port delivery system are becoming new tools in this war. The revolution and evolution of new delivery methods might be just a few steps ahead, yet its assimilation in our daily clinical work may take time, due to medical, economical, and regulatory elements that need to be met in order to allow successful development and market utilization of new technologies. Therefore, further work is warranted, as detailed in this Pharmaceutics Special Issue. Full article
(This article belongs to the Special Issue Recent Advances in Retinal Drug Delivery)
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20 pages, 1987 KiB  
Review
Nanotechnology for Age-Related Macular Degeneration
by Bo Yang, Ge Li, Jiaxin Liu, Xiangyu Li, Shixin Zhang, Fengying Sun and Wenhua Liu
Pharmaceutics 2021, 13(12), 2035; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122035 - 29 Nov 2021
Cited by 7 | Viewed by 3113
Abstract
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Advances in Retinal Drug Delivery)
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15 pages, 2052 KiB  
Review
Molecular Features of Classic Retinal Drugs, Retinal Therapeutic Targets and Emerging Treatments
by Alessandro Arrigo and Francesco Bandello
Pharmaceutics 2021, 13(7), 1102; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071102 - 20 Jul 2021
Cited by 10 | Viewed by 2724
Abstract
The management of exudative retinal diseases underwent a revolution due to the introduction of intravitreal treatments. There are two main classes of intravitreal drugs, namely anti-vascular endothelial growth factors (anti-VEGF) and corticosteroids molecules. The clinical course and the outcome of retinal diseases radically [...] Read more.
The management of exudative retinal diseases underwent a revolution due to the introduction of intravitreal treatments. There are two main classes of intravitreal drugs, namely anti-vascular endothelial growth factors (anti-VEGF) and corticosteroids molecules. The clinical course and the outcome of retinal diseases radically changed thanks to the efficacy of these molecules in determining the regression of the exudation and the restoration of the macular profile. In this review, we described the molecular features of classic retinal drugs, highlighting the main therapeutic targets, and we provided an overview of new emerging molecules. We performed a systematic review of the current literature available in the MEDLINE library, focusing on current intravitreal molecules and on new emerging therapies. The anti-VEGF molecules include Bevacizumab, Pegaptanib, Ranibizumab, Aflibercept, Conbercept, Brolucizumab, Abicipar-pegol and Faricimab. The corticosteroids approach is mainly based on the employment of triamcinolone acetonide, dexamethasone and fluocinolone acetonide molecules. Many clinical trials and real-life reports demonstrated their efficacy in exudative retinal diseases, highlighting differences in terms of molecular targeting and pharmacologic profiles. Furthermore, several new molecules are currently under investigation. Intravitreal drugs focus their activity on a wide range of therapeutic targets and are safe and efficacy in managing retinal diseases. Full article
(This article belongs to the Special Issue Recent Advances in Retinal Drug Delivery)
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18 pages, 1180 KiB  
Review
Drug Delivery via the Suprachoroidal Space for the Treatment of Retinal Diseases
by Liron Naftali Ben Haim and Elad Moisseiev
Pharmaceutics 2021, 13(7), 967; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13070967 - 26 Jun 2021
Cited by 30 | Viewed by 7132
Abstract
The suprachoroidal space (SCS), a potential space between the sclera and choroid, is becoming an applicable method to deliver therapeutics to the back of the eye. In recent years, a vast amount of research in the field has been carried out, with new [...] Read more.
The suprachoroidal space (SCS), a potential space between the sclera and choroid, is becoming an applicable method to deliver therapeutics to the back of the eye. In recent years, a vast amount of research in the field has been carried out, with new discoveries in different areas of interest, such as imaging, drug delivery methods, pharmacokinetics, pharmacotherapies in preclinical and clinical trials and advanced therapies. The SCS can be visualized via advanced techniques of optical coherence tomography (OCT) in eyes with different pathologies, and even in healthy eyes. Drugs can be delivered easily and safely via hollow microneedles fitted to the length of the approximate thickness of the sclera. SCS injections were found to reach greater baseline concentrations in the target layers compared to intravitreal (IVT) injection, while agent clearance was faster with highly aqueous soluble molecules. Clinical trials with SCS injection of triamcinolone acetonide (TA) were executed with promising findings for patients with noninfectious uveitis (NIU), NIU implicated with macular edema and diabetic macular edema (DME). Gene therapy is evolving rapidly with viral and non-viral vectors that were found to be safe and efficient in preclinical trials. Here, we review these novel different aspects and new developments in clinical treatment of the posterior segment of the eye. Full article
(This article belongs to the Special Issue Recent Advances in Retinal Drug Delivery)
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