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Pharmaceutics
Special Issues
Ocular Drug Delivery System
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Ocular Drug Delivery System

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

Deadline for manuscript submissions: 31 October 2026 | Viewed by 3708

Special Issue Editors

Dr. Xin Fan

E-Mail Website
Guest Editor
Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA 15260, USA
Interests: ocular drug delivery; tear biomarkers; biomaterials
Prof. Dr. Elena Sánchez-López

E-Mail Website
Guest Editor
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, Barcelona, Spain
Interests: drug delivery systems; nanoparticles; biodegradable nanoparticles; neurodegenerative diseases; ocular drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue on ocular drug delivery systems delves into the advancements and challenges in developing effective methods for treating several ocular diseases. Delivering drugs to the eye is fraught with difficulties due to its complex anatomical and physiological barriers, which hinder the delivery of therapeutic agents in adequate concentrations and for sufficient durations. This Special Issue aims to spotlight innovations that address these barriers, focusing on improving bioavailability, enhancing drug stability, and ensuring targeted delivery to specific ocular tissues. Recent progress in ocular drug delivery systems, including non-invasive and minimally invasive approaches, offers new hope for better patient outcomes. This Special Issue will cover cutting-edge developments in the field, from advanced materials for drug formulation to novel delivery methods, such as sustained-release systems, gene therapy, and retinal drug delivery. Research on diseases like age-related macular degeneration (AMD), glaucoma, diabetic retinopathy, and dry eye syndrome will also be explored, with emphasis on the need for personalized treatments that reduce side effects and improve patient compliance. This Special Issue invites the submission of high-quality research and review articles that address both basic science and clinical translation in ocular drug delivery. Its contributions will range from basic research on delivery mechanisms to translational studies and clinical applications, reflecting the interdisciplinary nature of this vital field in ophthalmology.

Dr. Xin Fan
Prof. Dr. Elena Sánchez-López
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 250 words) can be sent to the Editorial Office for assessment.

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

  • drug delivery
  • nanoparticles
  • controlled release
  • hydrogels
  • liposomes
  • microneedle arrays

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Published Papers (3 papers)

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Research

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16 pages, 1728 KB  
Article
Ocular and Systemic Pharmacokinetics of Baicalein and Baicalin After Intravitreal Injection and Oral Administration in Mice
by Yunshi Zhi, Li Pan, Wenjun Xiong, Thomas Chuen Lam, Huihui Xiao and Chi Wai Do
Pharmaceutics 2026, 18(2), 243; https://doi.org/10.3390/pharmaceutics18020243 - 15 Feb 2026
Viewed by 1188
Abstract
Background: Glaucoma requires therapies that extend beyond intraocular pressure (IOP)-lowering strategies, and baicalein (BA) offers dual IOP-lowering and neuroprotective potential. This study evaluated the pharmacokinetics of BA and its major metabolite baicalin (BG) in mouse eyes and serum after intravitreal (IVT) and oral [...] Read more.
Background: Glaucoma requires therapies that extend beyond intraocular pressure (IOP)-lowering strategies, and baicalein (BA) offers dual IOP-lowering and neuroprotective potential. This study evaluated the pharmacokinetics of BA and its major metabolite baicalin (BG) in mouse eyes and serum after intravitreal (IVT) and oral administration to determine whether non-invasive oral dosing can achieve IVT-comparable ocular exposure. Methods: BA was administered via IVT injection (100 μM) or oral gavage (20 and 200 mg/kg) in mice, and concentrations of BA and BG in serum and ocular tissues were quantified using a validated ultra-performance liquid chromatography–mass spectrometry (UHPLC/MS) method. Results: After IVT, ocular BA peaked at 331.56 ± 17.75 ng/g at 5 min and declined to 7.13 ± 0.79 ng/g at 4 h, with minimal systemic exposure. Oral administration achieved comparable or higher peak ocular BA levels (380.43 ± 52.85 ng/g at 15 min for 20 mg/kg; 309.70 ± 24.75 ng/g at 5 min for 200 mg/kg), with markedly higher ocular area under the concentration–time curve (AUC: 2455.48 ± 667.83 h·ng/g for 200 mg/kg and 1224.88 ± 751.13 h·ng/g for 20 mg/kg) versus IVT (247.07 h·ng/g). Serum BA and BG peaked at 5 min after oral dosing, with systemic BG exposure substantially exceeding BA. Conclusions: Non-invasive oral BA dosing achieves ocular concentrations comparable to IVT injection, with significantly greater overall exposure and favorable pharmacokinetic profiles. This study provides the first demonstration in mice that non-invasive oral BA administration can replace invasive IVT delivery, establishing a strong rationale for its clinical development in glaucoma and retinal disease management. Full article
(This article belongs to the Special Issue Ocular Drug Delivery System)
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26 pages, 2683 KB  
Article
Development of Brimonidine-Loaded Ethosomes for Glaucoma: Investigation of Intraocular Pressure-Lowering Potential In Vivo
by Samet Özdemir, Ali Asram Sağıroğlu, Eslim Şen, Büşra Gelmez Yıldız, Laman Karimli, Meltem Ezgi Durgun Kılıç, Ali Riza Cenk Celebi and Yıldız Özsoy
Pharmaceutics 2026, 18(2), 210; https://doi.org/10.3390/pharmaceutics18020210 - 6 Feb 2026
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Abstract
Background/Objectives: Brimonidine tartrate (BRT), a selective α2-adrenergic receptor agonist, is commonly used in the treatment of glaucoma. However, conventional eye drop formulations suffer from poor ocular bioavailability and rapid elimination. This study aimed to develop and evaluate BRT-loaded ethosomes as a nanocarrier-based [...] Read more.
Background/Objectives: Brimonidine tartrate (BRT), a selective α2-adrenergic receptor agonist, is commonly used in the treatment of glaucoma. However, conventional eye drop formulations suffer from poor ocular bioavailability and rapid elimination. This study aimed to develop and evaluate BRT-loaded ethosomes as a nanocarrier-based alternative to enhance intraocular delivery and therapeutic efficacy. Methods: Ethosomes were prepared using the thin-film hydration method and optimized via central composite design. The optimized formulation was subjected to physicochemical characterization, in vitro release testing, and ocular irritation assessment using the Hen egg test—chorioallantoic membrane (HET-CAM) model. Additionally, the intraocular pressure (IOP)-lowering efficacy of the formulation was evaluated in a rat glaucoma model. Results: The optimized ethosomal formulation exhibited favorable physicochemical properties, including a mean particle size of 122.6 ± 0.7 nm, zeta potential of −1.8 ± 0.9 mV, and encapsulation efficiency of 87.33 ± 0.04%. In vitro release data followed Higuchi kinetics. HET-CAM analysis indicated non-irritancy. In vivo, the ethosomal BRT formulation achieved comparable IOP-lowering effects to the marketed eye drops at one-third of the dose. Conclusions: The developed BRT-loaded ethosomal system demonstrated promising physicochemical stability, sustained release, and therapeutic potential. These findings suggest that ethosomes may offer a safe and effective strategy for enhancing the ocular delivery of BRT in glaucoma therapy. Full article
(This article belongs to the Special Issue Ocular Drug Delivery System)
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Review

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24 pages, 1239 KB  
Review
Anatomically Guided Non-Viral CRISPR/Cas9 Delivery in the Eye: Overcoming Barriers for Precision Gene Therapy
by Zhixiang Hua, Yang Shen and Xingtao Zhou
Pharmaceutics 2026, 18(3), 282; https://doi.org/10.3390/pharmaceutics18030282 - 24 Feb 2026
Viewed by 1001
Abstract
Background/Objectives: While CRISPR/Cas9 technology offers a revolutionary approach for correcting genetic ocular blindness, efficient and safe delivery remains the primary bottleneck. Traditional viral vectors, despite their efficacy, face challenges regarding cargo size limitations and potential genomic integration risks. Non-viral vectors offer distinct comparative [...] Read more.
Background/Objectives: While CRISPR/Cas9 technology offers a revolutionary approach for correcting genetic ocular blindness, efficient and safe delivery remains the primary bottleneck. Traditional viral vectors, despite their efficacy, face challenges regarding cargo size limitations and potential genomic integration risks. Non-viral vectors offer distinct comparative advantages, including large cargo capacity for diverse CRISPR tools and transient expression to minimize off-target effects, but must overcome the eye’s formidable static and dynamic barriers, specifically the corneal epithelium, vitreous humor, and the inner limiting membrane. In this review, we present an anatomically guided framework for non-viral CRISPR/Cas9 delivery, mapping engineering strategies to specific ocular tissue targets. We first delineate the mechanisms of key physiological barriers, including the corneal stroma, aqueous humor circulation, and the vitreous–retina interface. Subsequently, we critically evaluate the latest advancements in non-viral platforms, such as pH-responsive lipid nanoparticles and engineered virus-like particles. The core focus of this review is on site-specific breakthrough strategies: from utilizing mucoadhesive polymers to counteract tear clearance in the cornea to exploiting specialized administration routes, such as suprachoroidal space and subretinal injection, to bypass retinal barriers, and deep-penetrating intravitreal carriers for targeting the photoreceptor-RPE complex. By integrating material science with precise administration routes, this review highlights feasible translational pathways for next-generation, carrier-free, or biomimetic ocular gene editing therapies. Full article
(This article belongs to the Special Issue Ocular Drug Delivery System)
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