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

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 (28 February 2022) | Viewed by 21381

Special Issue Editors

Prof. Dr. María Ángeles Solinís

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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: 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
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ana Del Pozo-Rodríguez

E-Mail Website
Guest Editor
Universidad del Pais Vasco—Euskal Herriko Unibertsitatea, Campus Álava, Nanotechnology and Gene Therapy Group (PharmaNanoGene), 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

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

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

  • 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

Published Papers (7 papers)

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Research

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16 pages, 7966 KiB  
Article
Dextran Sulfate Polymer Wafer Promotes Corneal Wound Healing
by Remya Ammassam Veettil, Daniela C. Marcano, Xiaoyong Yuan, Mahira Zaheer, Aparna Adumbumkulath, Richard Lee, Lucas C. Isenhart, Nicole Soriano, Kirti Mhatre, Robiya Joseph, Sendurai A. Mani, Crystal S. Shin and Ghanashyam Acharya
Pharmaceutics 2021, 13(10), 1628; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101628 - 06 Oct 2021
Cited by 5 | Viewed by 2263
Abstract
Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid [...] Read more.
Eye injuries due to corneal abrasions, chemical spills, penetrating wounds, and microbial infections cause corneal scarring and opacification that result in impaired vision or blindness. However, presently available eye drop formulations of anti-inflammatory and antibiotic drugs are not effective due to their rapid clearance from the ocular surface or due to drug-related side effects such as cataract formation or increased intraocular pressure. In this article, we presented the development of a dextran sulfate-based polymer wafer (DS-wafer) for the effective modulation of inflammation and fibrosis and demonstrated its efficacy in two corneal injury models: corneal abrasion mouse model and alkali induced ocular burn mouse model. The DS-wafers were fabricated by the electrospinning method. We assessed the efficacy of the DS-wafer by light microscopy, qPCR, confocal fluorescence imaging, and histopathological analysis. These studies demonstrated that the DS-wafer treatment is significantly effective in modulating corneal inflammation and fibrosis and inhibited corneal scarring and opacification compared to the unsulfated dextran-wafer treated and untreated corneas. Furthermore, these studies have demonstrated the efficacy of dextran sulfate as an anti-inflammatory and antifibrotic polymer therapeutic. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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22 pages, 2902 KiB  
Article
mRNA-Based Nanomedicinal Products to Address Corneal Inflammation by Interleukin-10 Supplementation
by Itziar Gómez-Aguado, Julen Rodríguez-Castejón, Marina Beraza-Millor, Mónica Vicente-Pascual, Alicia Rodríguez-Gascón, Sara Garelli, Luigi Battaglia, Ana del Pozo-Rodríguez and María Ángeles Solinís
Pharmaceutics 2021, 13(9), 1472; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091472 - 15 Sep 2021
Cited by 10 | Viewed by 3263
Abstract
The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 [...] Read more.
The anti-inflammatory cytokine Interleukin-10 (IL-10) is considered an efficient treatment for corneal inflammation, in spite of its short half-life and poor eye bioavailability. In the present work, mRNA-based nanomedicinal products based on solid lipid nanoparticles (SLNs) were developed in order to produce IL-10 to treat corneal inflammation. mRNA encoding green fluorescent protein (GFP) or human IL-10 was complexed with different SLNs and ligands. After, physicochemical characterization, transfection efficacy, intracellular disposition, cellular uptake and IL-10 expression of the nanosystems were evaluated in vitro in human corneal epithelial (HCE-2) cells. Energy-dependent mechanisms favoured HCE-2 transfection, whereas protein production was influenced by energy-independent uptake mechanisms. Nanovectors with a mean particle size between 94 and 348 nm and a positive superficial charge were formulated as eye drops containing 1% (w/v) of polyvinyl alcohol (PVA) with 7.1–7.5 pH. After three days of topical administration to mice, all formulations produced GFP in the corneal epithelium of mice. SLNs allowed the obtaining of a higher transfection efficiency than naked mRNA. All formulations produce IL-10, and the interleukin was even observed in the deeper layers of the epithelium of mice depending on the formulation. This work shows the potential application of mRNA-SLN-based nanosystems to address corneal inflammation by gene augmentation therapy. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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13 pages, 2293 KiB  
Article
Preclinical Evaluations of Modified Rice Hydrogel for Topical Ophthalmic Drug Delivery of Praziquantel on Avian Philophalmiasis
by Treepecth Prompetch, Akawat Chailorm, Saruda Tiwananthagorn, Nithidol Buranapim, Siriporn Okonogi, Hirotomo Kato, Wasan Katip and Raktham Mektrirat
Pharmaceutics 2021, 13(7), 952; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13070952 - 24 Jun 2021
Cited by 2 | Viewed by 2019
Abstract
The present study aims to evaluate the efficacy of a novel drug delivery system of the modified rice hydrogel containing praziquantel (PZQ) against Philophthalmus gralli isolated from ostrich eyes and determine the toxicity of the preparation on chicken eye model. The parasiticidal activity [...] Read more.
The present study aims to evaluate the efficacy of a novel drug delivery system of the modified rice hydrogel containing praziquantel (PZQ) against Philophthalmus gralli isolated from ostrich eyes and determine the toxicity of the preparation on chicken eye model. The parasiticidal activity of PZQ (0, 1, 10, and 100 µg/mL) was tested on P. gralli. The ophthalmic antiparasitic hydrogel was formulated with appropriate amount of PZQ and chemically modified rice gel. The parasitic morphology after exposure with the preparation was examined under scanning electron microscope (SEM). The anthelminthic efficacy of the preparation on motility and mortality of parasites was performed by visual inspection and vital dye staining. The ocular irritation of the preparation was evaluated for 21 days using standard avian model followed by OECD 405. The results demonstrated that the parasiticidal activity of PZQ against P. gralli appears to be in a concentration- and time-dependent manner. In addition, the concentration of PZQ 10 µg/mL (Chi squared test, p = 0.003) and exposure time for 24 h (log-rank test, p = 0.0004) is sufficient to kill parasites, when statistically compared to negative control group. Rice hydrogel containing a lethal concentration of 10 µg/mL PZQ was successfully prepared. The preparation illustrated good parasitic killing and motile inhibiting effect on P. gralli compared with PZQ 10 µg/mL and its control (p < 0.05). An appearance under SEM of non-viable parasite after being incubated with the preparation, showing parasitic deformity, was observed comparing with the viable parasite in 0.9% normal saline solution (NSS). Moreover, no irritation of chicken eyes was also observed. Our results contribute to understanding the efficacy and the safety of the rice hydrogel of PZQ which have a predictive value for controlling P. gralli on the animal eyes. However, the pharmacological application needs to be further investigated for the best possible therapeutic approach. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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14 pages, 14401 KiB  
Article
Maturation and Protection Effect of Retinal Tissue-Derived Bioink for 3D Cell Printing Technology
by Jongmin Kim, Jeong Sik Kong, Hyeonji Kim, Wonil Han, Jae Yon Won and Dong-Woo Cho
Pharmaceutics 2021, 13(7), 934; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13070934 - 23 Jun 2021
Cited by 6 | Viewed by 2572
Abstract
Retinal degeneration is a leading cause of incurable vision loss and blindness. The increasing incidence of retinal degeneration has triggered research into the development of in vitro retinal models for drug development and retinal alternatives for transplantation. However, the complex retinal structure and [...] Read more.
Retinal degeneration is a leading cause of incurable vision loss and blindness. The increasing incidence of retinal degeneration has triggered research into the development of in vitro retinal models for drug development and retinal alternatives for transplantation. However, the complex retinal structure and the retinal microenvironment pose serious challenges. Although 3D cell printing technology has been widely used in tissue engineering, including in vitro model development and regeneration medicine, currently available bioinks are insufficient to recapitulate the complex extracellular matrix environment of the retina. Therefore, in this study, we developed a retinal decellularized extracellular matrix (RdECM) from the porcine retina and evaluated its characteristics. The RdECM conserved the ECM components from the native retina without cellular components. Then, we mixed the RdECM with collagen to form a bioink and confirmed its suitability for 3D cell printing. We further studied the effect of the RdECM bioink on the differentiation of Muller cells. The retinal protective effect of the RdECM bioink was confirmed through a retinal degeneration animal model. Thus, we believe that the RdECM bioink is a promising candidate for retinal tissue engineering. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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19 pages, 2384 KiB  
Article
Ion-Complex Microcrystal Formulation Provides Sustained Delivery of a Multimodal Kinase Inhibitor from the Subconjunctival Space for Protection of Retinal Ganglion Cells
by Henry T. Hsueh, Yoo-Chun Kim, Ian Pitha, Matthew D. Shin, Cynthia A. Berlinicke, Renee Ti Chou, Elizabeth Kimball, Julie Schaub, Sarah Quillen, Kirby T. Leo, Hyounkoo Han, Amy Xiao, Youngwook Kim, Matthew Appell, Usha Rai, HyeYoung Kwon, Patricia Kolodziejski, Laolu Ogunnaike, Nicole M. Anders, Avelina Hemingway, Joan L. Jefferys, Abhijit A. Date, Charles Eberhart, Thomas V. Johnson, Harry A. Quigley, Donald J. Zack, Justin Hanes and Laura M. Ensignadd Show full author list remove Hide full author list
Pharmaceutics 2021, 13(5), 647; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050647 - 01 May 2021
Cited by 10 | Viewed by 3494
Abstract
Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may [...] Read more.
Glaucoma is the leading cause of irreversible blindness worldwide. Elevated intraocular pressure (IOP) is one of the major risk factors for glaucoma onset and progression, and available pharmaceutical interventions are exclusively targeted at IOP lowering. However, degeneration of retinal ganglion cells (RGCs) may continue to progress despite extensive lowering of IOP. A complementary strategy to IOP reduction is the use of neuroprotective agents that interrupt the process of cell death by mechanisms independent of IOP. Here, we describe an ion complexation approach for formulating microcrystals containing ~50% loading of a protein kinase inhibitor, sunitinib, to enhance survival of RGCs with subconjunctival injection. A single subconjunctival injection of sunitinib-pamoate complex (SPC) microcrystals provided 20 weeks of sustained retina drug levels, leading to neuroprotection in a rat model of optic nerve injury. Furthermore, subconjunctival injection of SPC microcrystals also led to therapeutic effects in a rat model of corneal neovascularization. Importantly, therapeutically relevant retina drug concentrations were achieved with subconjunctival injection of SPC microcrystals in pigs. For a chronic disease such as glaucoma, a formulation that provides sustained therapeutic effects to complement IOP lowering therapies could provide improved disease management and promote patient quality of life. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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10 pages, 3362 KiB  
Article
Development of an In Vitro Blink Model for Ophthalmic Drug Delivery
by Chau-Minh Phan, Manish Shukla, Hendrik Walther, Miriam Heynen, David Suh and Lyndon Jones
Pharmaceutics 2021, 13(3), 300; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13030300 - 25 Feb 2021
Cited by 11 | Viewed by 2596
Abstract
Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model [...] Read more.
Purpose: The purpose of this study was to develop an advanced in vitro blink model that can be used to examine the release of a wide variety of components (for example, topical ophthalmic drugs, comfort-inducing agents) from soft contact lenses. Methods: The model was designed using computer-aided design software and printed using a stereolithography 3D printer. The eyelid and eyeball were synthesized from polyvinyl alcohol and silicone material, respectively. Simulated tear fluid was infused through tubing attached to the eyelid using a syringe pump. With each blink cycle, the eyelid slides and flexes across the eyeball to create an artificial tear film layer. The flow-through fluid was collected using a specialized trough. Two contact lenses, etafilcon A and senofilcon A, were incubated in 2 mL of a water-soluble red dye for 24 h and then placed on the eye model (n = 3). The release of the dye was measured over 24 h using a tear flow rate of 5 µL/min. Results: Approximately 25% of the fluid that flowed over the eye model was lost due to evaporation, nonspecific absorption, and residual dead volume. Senofilcon A absorbed more dye (47.6 ± 2.7 µL) than etafilcon A (22.3 ± 2.0 µL). For etafilcon A, the release of the dye followed a burst-plateau profile in the vial but was sustained in the eye model. For senofilcon A, the release of the dye was sustained in both the vial and the eye model, though more dye was released in the vial (p < 0.05). Overall, the release of the dye from the contact lenses was higher in the vial compared with the eye model (p < 0.05). Conclusion: The blink model developed in this study could be used to measure the release of topical ophthalmic drugs or comfort agents from contact lenses. Simulation of a blink mechanism, an artificial tear film, and nonspecific absorption in an eye model may provide better results than a simple, static vial incubation model. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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Review

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17 pages, 1113 KiB  
Review
A Review of Ocular Drug Delivery Platforms and Drugs for Infectious and Noninfectious Uveitis: The Past, Present, and Future
by Christopher D. Conrady and Steven Yeh
Pharmaceutics 2021, 13(8), 1224; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081224 - 08 Aug 2021
Cited by 11 | Viewed by 3171
Abstract
Uveitis refers to a broad group of inflammatory disorders of the eye that often require medical and surgical management to improve or stabilize vision and prevent vision-threatening pathological changes to the eye. Drug delivery to the eye to combat inflammation and subsequent complications [...] Read more.
Uveitis refers to a broad group of inflammatory disorders of the eye that often require medical and surgical management to improve or stabilize vision and prevent vision-threatening pathological changes to the eye. Drug delivery to the eye to combat inflammation and subsequent complications from uveitic conditions is complex as there are multiple barriers to absorption limiting availability of the needed drug in the affected tissues. As such, there has been substantial interest in developing new drugs and drug delivery platforms to help reduce intraocular inflammation and its complications. In this review, we discuss the challenges of drug delivery, novel technologies recently approved for uveitis patient care and promising drug delivery platforms for uveitis and sequelae of ocular inflammation. Full article
(This article belongs to the Special Issue Ocular Drug Delivery: Present Innovations and Future Challenges (Volume II))
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