Ophthalmic Drug Delivery, 2nd Edition

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 (30 November 2022) | Viewed by 55598

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
Interests: ocular drug delivery; ocular pharmacokinetic; drug development; pharmacogenetics; clinical and translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Research in ophthalmic drug delivery has developed significant advances in the last years, and efforts have been made to develop more effective topical formulations to increase drug bioavailability, efficiency, and safety. Drug delivery to the posterior segment of the eye remains a great challenge in the pharmaceutical industry due to the complexity and particularity of the anatomy and physiology of the eye. Some advances have been made with the purpose of maintaining constant drug levels in the site of action. The anatomical ocular barriers have a great impact on drug pharmacokinetics and, subsequently, on the pharmacological effect.

Despite the increasing interest in efficiently reaching the posterior segment of the eye with reduced adverse effects, there is still a need to expand the knowledge of ocular pharmacokinetics that allow the development of safer and more innovative drug delivery systems. These novel approaches may greatly help to improve the lives of patients with ocular pathologies.

In this Special Issue, our goal is to highlight papers describing the advances in ophthalmic drug delivery systems for topical and specialized ocular administration.

Prof. Dr. Francisco Javier Otero-Espinar
Dr. Anxo Fernández Ferreiro
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 pharmacokinetics
  • ocular drug delivery systems
  • ocular routs of drug administration
  • intravitreal administration
  • topical administration

Related Special Issues

Published Papers (18 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

14 pages, 5131 KiB  
Article
Topical Sustained Delivery of Miltefosine Via Drug-Eluting Contact Lenses to Treat Acanthamoeba Keratitis
by Lin Chen, Liangju Kuang, Amy E. Ross, Wissam Farhat, Nikolay Boychev, Sina Sharfi, Levi N. Kanu, Longqian Liu, Daniel S. Kohane and Joseph B. Ciolino
Pharmaceutics 2022, 14(12), 2750; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14122750 - 08 Dec 2022
Cited by 2 | Viewed by 1597
Abstract
This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of [...] Read more.
This study aimed to develop a miltefosine-eluting contact lens (MLF-CL) device that would allow sustained and localized miltefosine release for the treatment of Acanthamoeba keratitis. MLF-CLs were produced in three different miltefosine doses by solvent-casting a thin miltefosine-polymer film around the periphery of a methafilcon hydrogel, which was then lathed into a contact lens. During seven days of in vitro testing, all three formulations demonstrated sustained release from the lens at theoretically therapeutic levels. Based on the physicochemical characterization of MLF-CLs, MLF-CL’s physical properties are not significantly different from commercial contact lenses in terms of light transmittance, water content and wettability. MLF-CLs possessed a slight reduction in compression modulus that was attributed to the inclusion of polymer-drug films but still remain within the optimal range of soft contact lenses. In cytotoxicity studies, MLF-CL indicated up to 91% viability, which decreased proportionally as miltefosine loading increased. A three-day biocompatibility test on New Zealand White rabbits revealed no impact of MLF-CLs on the corneal tissue. The MLF-CLs provided sustained in vitro release of miltefosine for a week while maintaining comparable physical features to a commercial contact lens. MLF-CL has a promising potential to be used as a successful treatment method for Acanthamoeba keratitis. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

21 pages, 3288 KiB  
Article
Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation
by José Izo Santana da Silva de Jesus, Felipe Rebello Lourenço, Kelly Ishida, Thayná Lopes Barreto, Valdir Carlos Avino, Edson dos Santos Neto and Nádia Araci Bou-Chacra
Pharmaceutics 2022, 14(10), 2221; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14102221 - 18 Oct 2022
Cited by 4 | Viewed by 1428
Abstract
Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly [...] Read more.
Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly used for treatment. Among the most recent antibiotics, besifloxacin is a fourth-generation fluoroquinolone antibiotic indicated exclusively for topical ophthalmic use. Due to its importance in treating bacterial conjunctivitis and its low solubility in water, limiting its efficacy, a nanotechnology-based drug delivery preparation was developed to overcome this hurdle. Besifloxacin nanocrystals were prepared by small-scale wet milling and response surface methodology, using Povacoat® as a stabilizer. The particle’s average hydrodynamic diameter (Z-ave) was approximately 550 nm (17 times smaller than raw material), with a polydispersity index (PdI) of less than 0.2. The saturation solubility increased about two times compared to the raw material, making it possible to increase the dissolution rate of this drug substance, potentially improving its bioavailability and safety. The optimized preparation was stable under an accelerated stability study (90 days). The Z-ave, PZ, PdI, and content did not alter significantly during this period. Furthermore, the 0.6% m/m besifloxacin nanocrystals at the maximum dose and the Povacoat® stabilizer did not show toxicity in Galleria mellonella larvae. The innovative ophthalmic preparation minimum inhibitory concentration (MIC) was 0.0960 µg/mL and 1.60 µg/mL against Staphylococcus aureus and Pseudomonas aeruginosa, respectively, confirming in vitro efficacy. Therefore, besifloxacin nanocrystals revealed the potential for reduced dosing of the drug substance, with a minor occurrence of adverse effects and greater patient adherence to treatment. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

18 pages, 2850 KiB  
Article
Cysteamine Eye Drops in Hyaluronic Acid Packaged in Innovative Single-Dose Systems: Stability and Ocular Biopermanence
by Ana Castro-Balado, Enrique Bandín-Vilar, Andrea Cuartero-Martínez, Laura García-Quintanilla, Gonzalo Hermelo-Vidal, Xurxo García-Otero, Lorena Rodríguez-Martínez, Jesús Mateos, Manuela Hernández-Blanco, Pablo Aguiar, Irene Zarra-Ferro, Miguel González-Barcia, Cristina Mondelo-García, Francisco J. Otero-Espinar and Anxo Fernández-Ferreiro
Pharmaceutics 2022, 14(10), 2194; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14102194 - 15 Oct 2022
Cited by 2 | Viewed by 2184
Abstract
Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that [...] Read more.
Cystinosis is a rare genetic disorder characterized by the accumulation of cystine crystals in different tissues and organs causing, among other symptoms, severe ocular manifestations. Cysteamine eye drops are prepared in hospital pharmacy departments to facilitate access to treatment, for which vehicles that provide adequate biopermanence, as well as adaptable containers that maintain its stability, are required. Difficulties related to cysteamine preparation, as well as its tendency to oxidize to cystamine, show the importance of conducting rigorous galenic characterization studies. This work aims to develop and characterize an ophthalmic compounded formulation of cysteamine prepared with hyaluronic acid and packaged in innovative single-dose systems. For this task, the effect of different storage temperatures and the presence/absence of nitrogen on the physicochemical stability of the formulation and its packaging was studied in a scaled manner, until reaching the optimal storage conditions. The results showed that 0.55% cysteamine, prepared with hyaluronic acid and packaged in single-dose containers, is stable for 30 days when stored at −20 °C. In addition, opening vials every 4 h at room temperature after 30 days of freezing maintains the stability of the cysteamine formulation for up to 16 h. Moreover, ocular biopermanence studies were conducted using molecular imaging, concluding that the biopermanence offered by the vehicle is not affected by the freezing process, where a half-life of 31.11 min for a hyaluronic acid formulation stored for 30 days at −20 °C was obtained, compared with 14.63 min for 0.9% sodium chloride eye drops. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

25 pages, 7958 KiB  
Article
Mucoadhesive PLGA Nanospheres and Nanocapsules for Lactoferrin Controlled Ocular Delivery
by Rubén Varela-Fernández, Xurxo García-Otero, Victoria Díaz-Tomé, Uxía Regueiro, Maite López-López, Miguel González-Barcia, María Isabel Lema and Francisco Javier Otero-Espinar
Pharmaceutics 2022, 14(4), 799; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14040799 - 06 Apr 2022
Cited by 11 | Viewed by 2456
Abstract
Background: the present work describes the preparation, characterization and optimization of eight types of PLGA-based nanosystems (nanospheres and nanocapsules) as innovative mucoadhesive drug delivery systems of lactoferrin, in order to achieve a preclinical consistent base as an alternative pharmacological treatment to different ocular [...] Read more.
Background: the present work describes the preparation, characterization and optimization of eight types of PLGA-based nanosystems (nanospheres and nanocapsules) as innovative mucoadhesive drug delivery systems of lactoferrin, in order to achieve a preclinical consistent base as an alternative pharmacological treatment to different ocular syndromes and diseases. Methods: All different nanoparticles were prepared via two modified nanoprecipitation techniques, using a three-component mixture of drug/polymer/surfactant (Lf/PLGA/Poloxamer), as a way to overcome the inherent limitations of conventional PLGA NPs. These modified polymeric nanocarriers, intended for topical ophthalmic administration, were subjected to in vitro characterization, surface modification and in vitro and in vivo assessments. Results: An appropriate size range, uniform size distribution and negative ζ potential values were obtained for all types of formulations. Lactoferrin could be effectively included into all types of nanoparticles with appropriate encapsulation efficiency and loading capacity values. A greater, extended, and controlled delivery of Lf from the polymeric matrix was observed through the in vitro release studies. No instability or cytotoxicity was proved for all the formulations by means of organotypic models. Additionally, mucoadhesive in vitro and in vivo experiments show a significant increase in the residence time of the nanoparticles in the eye surface. Conclusions: all types of prepared PLGA nanoparticles might be a potential alternative for the topical ophthalmic administration of lactoferrin. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

23 pages, 6270 KiB  
Article
Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases
by Marion Barrieu, Philip Chennell, Mouloud Yessaad, Yassine Bouattour, Mathieu Wasiak, Mireille Jouannet, Yoann Le Basle and Valérie Sautou
Pharmaceutics 2022, 14(1), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14010118 - 04 Jan 2022
Cited by 6 | Viewed by 2971
Abstract
Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability [...] Read more.
Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

12 pages, 2355 KiB  
Article
Anti-Inflammatory Effect of Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drops in an Endotoxin-Induced Uveitis Model
by Xurxo García-Otero, Cristina Mondelo-García, Francisco González, Roman Perez-Fernandez, Leandro Avila, Jose Ramón Antúnez-López, Miguel González-Barcia, Alfredo Adan, Pablo Aguiar, Francisco J. Otero-Espinar, Maria A. Bermúdez and Anxo Fernández-Ferreiro
Pharmaceutics 2021, 13(10), 1737; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101737 - 19 Oct 2021
Cited by 7 | Viewed by 2634
Abstract
Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of contraindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has [...] Read more.
Background: Uveitis is an infrequent disease which constitutes a major cause of ocular morbidity. Correct management is essential, being corticosteroids its cornerstone. In case of contraindication to corticosteroids or treatment failure, the use of topical tacrolimus (TAC) could be an alternative which has already demonstrated safety and effectiveness in other ocular pathologies. However, TAC eye drops are not marketed, thus their elaboration must be carried out in Hospital Pharmacy Departments (HPDs). Methods: 32 Sprague-Dawley rats were divided into 4 groups of 8 rats each: (a) untreated healthy rats (Healthy); (b) untreated Endotoxin-Induced Uveitis model-rats (EIU); (c) EIU-rats treated with standard treatment of dexamethasone ophthalmic drops (DXM) and (d) EIU-rats treated with TAC-hydroxypropyl-β-cyclodextrin eye drops previously developed by our group (TAC-HPβCD). The mRNA expression levels of IL-6, IL-8, MIP-1α and TNF-α, quantitative analysis of leucocytes in aqueous humor and histological evaluation were performed. Results: TAC-HPβCD eye drops demonstrated to reduce ocular inflammation, expression of IL-6, TNF-α, MIP-1α and leukocyte infiltration in aqueous humor. Conclusions: TAC-HPβCD eye drops showed beneficial effect in EIU model in rats, positioning as an alternative for uveitis treatment in case of corticosteroids resistance or intolerance. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

10 pages, 3109 KiB  
Article
Sustained-Release Microspheres of Rivoceranib for the Treatment of Subfoveal Choroidal Neovascularization
by E Seul Kim, Min Sang Lee, Hayoung Jeong, Su Yeon Lim, Doha Kim, Dahwun Kim, Jaeback Jung, Siyan Lyu, Hee Joo Cho, Dong Min Kim, Wonhee Suh and Ji Hoon Jeong
Pharmaceutics 2021, 13(10), 1548; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13101548 - 24 Sep 2021
Cited by 2 | Viewed by 2843
Abstract
The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial [...] Read more.
The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial role in the pathogenesis of the disease. In this study, we tried to repurpose an investigational anticancer drug, rivoceranib, which is a selective inhibitor of VEGF receptor-2 (VEGFR2), and evaluate the therapeutic potential of the drug for the treatment of wet-type AMD in a laser-induced CNV mouse model using microsphere-based sustained drug release formulations. The PLGA-based rivoceranib microsphere can carry out a sustained delivery of rivoceranib for 50 days. When administered intravitreally, the sustained microsphere formulation of rivoceranib effectively inhibited the formation of subfoveal neovascular lesions in mice. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

13 pages, 1477 KiB  
Article
Comprehensive Evidence of Carrier-Mediated Distribution of Amantadine to the Retina across the Blood–Retinal Barrier in Rats
by Yusuke Shinozaki, Shin-ichi Akanuma, Yuika Mori, Yoshiyuki Kubo and Ken-ichi Hosoya
Pharmaceutics 2021, 13(9), 1339; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091339 - 26 Aug 2021
Cited by 6 | Viewed by 2222
Abstract
Amantadine, a drug used for the blockage of NMDA receptors, is well-known to exhibit neuroprotective effects. Accordingly, assessment of amantadine transport at retinal barriers could result in the application of amantadine for retinal diseases such as glaucoma. The objective of this study was [...] Read more.
Amantadine, a drug used for the blockage of NMDA receptors, is well-known to exhibit neuroprotective effects. Accordingly, assessment of amantadine transport at retinal barriers could result in the application of amantadine for retinal diseases such as glaucoma. The objective of this study was to elucidate the retinal distribution of amantadine across the inner and outer blood–retinal barrier (BRB). In vivo blood-to-retina [3H]amantadine transport was investigated by using the rat retinal uptake index method, which was significantly reduced by unlabeled amantadine. This result indicated the involvement of carrier-mediated processes in the retinal distribution of amantadine. In addition, in vitro model cells of the inner and outer BRB (TR-iBRB2 and RPE-J cells) exhibited saturable kinetics (Km in TR-iBRB2 cells, 79.4 µM; Km in RPE-J cells, 90.5 and 9830 µM). The inhibition of [3H]amantadine uptake by cationic drugs/compounds indicated a minor contribution of transport systems that accept cationic drugs (e.g., verapamil), as well as solute carrier (SLC) organic cation transporters. Collectively, these outcomes suggest that carrier-mediated transport systems, which differ from reported transporters and mechanisms, play a crucial role in the retinal distribution of amantadine across the inner/outer BRB. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

15 pages, 2012 KiB  
Article
Investigating Ex Vivo Animal Models to Test the Performance of Intravitreal Liposomal Drug Delivery Systems
by Gustav Christensen, Leon Barut, Dileep Urimi, Nicolaas Schipper and François Paquet-Durand
Pharmaceutics 2021, 13(7), 1013; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13071013 - 02 Jul 2021
Cited by 14 | Viewed by 3054
Abstract
There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh [...] Read more.
There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh porcine eyes obtained from the local slaughterhouse as a model for testing the intravitreal biodistribution and retention of liposomes with or without polyethylene glycol (PEG) conjugation and with different surface charges. The histology of the eyes was analyzed to localize the liposomes, and it was found that liposomes with PEG absorbed rapidly on the retina (within 1 h), with positively charged and PEG-coated liposomes being retained for at least 24 h. In parallel, fluorophotometry was employed on intact eyes, to determine the pharmacokinetics of the fluorophore calcein, as a substitute for a small hydrophilic therapeutic compound. We found a 4.5-fold increase in the vitreous half-life of calcein loaded in liposomes, compared with the free solution. Retinal toxicity was addressed using murine-derived retinal explant cultures. Liposomes were non-toxic up to 500 µg/mL. Toxicity was observed at 5 mg/mL for anionic and cationic liposomes, with 2-fold and 2.5-fold increased photoreceptor cell death, respectively. Overall, we could show that important ocular drug delivery considerations such as pharmacokinetics and biodistribution can be estimated in ex vivo porcine eyes, and may guide subsequent in vivo experiments. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

17 pages, 2819 KiB  
Article
Distribution of Gold Nanoparticles in the Anterior Chamber of the Eye after Intracameral Injection for Glaucoma Therapy
by Tobias Sonntag, Franziska Froemel, W. Daniel Stamer, Andreas Ohlmann, Rudolf Fuchshofer and Miriam Breunig
Pharmaceutics 2021, 13(6), 901; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13060901 - 17 Jun 2021
Cited by 8 | Viewed by 2922
Abstract
In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the [...] Read more.
In glaucoma therapy, nanoparticles (NPs) are a favorable tool for delivering drugs to the outflow tissues of the anterior chamber of the eye where disease development and progression take place. In this context, a prerequisite is an efficient enrichment of NPs in the trabecular meshwork with minimal accumulation in off-target tissues such as the cornea, lens, iris and ciliary body. We evaluated the optimal size for targeting the trabecular meshwork by using gold NPs of 5, 60, 80 and 120 nm with a bare surface (AuNPs) or coated with hyaluronic acid (HA-AuNPs). NPs were compared regarding their colloidal stability, distribution in the anterior chamber of the eye ex vivo and cellular uptake in vitro. HA-AuNPs demonstrated an exceptional colloidal stability. Even after application into porcine eyes ex vivo, the HA coating prevented an aggregation of NPs inside the trabecular meshwork. NPs with a diameter of 120 nm exhibited the highest volume-based accumulation in the trabecular meshwork. Off-target tissues in the anterior chamber demonstrated an exceptionally low gold content. Our findings are particularly important for NPs with encapsulated anti-glaucoma drugs because a higher particle volume would be accompanied by a higher drug payload. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

11 pages, 708 KiB  
Article
Permeability of the Retina and RPE-Choroid-Sclera to Three Ophthalmic Drugs and the Associated Factors
by Hyeong Min Kim, Hyounkoo Han, Hye Kyoung Hong, Ji Hyun Park, Kyu Hyung Park, Hyuncheol Kim and Se Joon Woo
Pharmaceutics 2021, 13(5), 655; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13050655 - 04 May 2021
Cited by 8 | Viewed by 1732
Abstract
In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time–concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the [...] Read more.
In this study, Retina-RPE-Choroid-Sclera (RCS) and RPE-Choroid-Sclera (CS) were prepared by scraping them off neural retina, and using the Ussing chamber we measured the average time–concentration values in the acceptor chamber across five isolated rabbit tissues for each drug molecule. We determined the outward direction permeability of the RCS and CS and calculated the neural retina permeability. The permeability coefficients of RCS and CS were as follows: ganciclovir, 13.78 ± 5.82 and 23.22 ± 9.74; brimonidine, 15.34 ± 7.64 and 31.56 ± 12.46; bevacizumab, 0.0136 ± 0.0059 and 0.0612 ± 0.0264 (×10−6 cm/s). The calculated permeability coefficients of the neural retina were as follows: ganciclovir, 33.89 ± 12.64; brimonidine, 29.83 ± 11.58; bevacizumab, 0.0205 ± 0.0074 (×10−6 cm/s). Between brimonidine and ganciclovir, lipophilic brimonidine presented better RCS and CS permeability, whereas ganciclovir showed better calculated neural retinal permeability. The large molecular weight drug bevacizumab demonstrated a much lower permeability than brimonidine and ganciclovir. In conclusion, the ophthalmic drug permeability of RCS and CS is affected by the molecular weight and lipophilicity, and influences the intravitreal half-life. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

14 pages, 3495 KiB  
Article
Comparative Analysis of Morphological and Release Profiles in Ocular Implants of Acetazolamide Prepared by Electrospinning
by Mariana Morais, Patrícia Coimbra and Maria Eugénia Pina
Pharmaceutics 2021, 13(2), 260; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020260 - 15 Feb 2021
Cited by 12 | Viewed by 2175
Abstract
The visual impairment that often leads to blindness causes a higher morbidity rate. The goal of this work is to create a novel biodegradable polymeric implant obtained from coaxial fibers containing the dispersed drug—acetazolamide—in order to achieve sustained drug release and increase patient [...] Read more.
The visual impairment that often leads to blindness causes a higher morbidity rate. The goal of this work is to create a novel biodegradable polymeric implant obtained from coaxial fibers containing the dispersed drug—acetazolamide—in order to achieve sustained drug release and increase patient compliance, which is of the highest importance. Firstly, during this work, uncoated implants were produced by electrospinning, and rolled in the shape of small cylinders that were composed of uniaxial and coaxial fibers with immobilized drug inside. The fibers were composed by PCL (poly ε-caprolactone) and Lutrol F127 (poly (oxyethylene-b-oxypropylene-b-oxyethylene)). The prepared implants exhibited a fast rate of drug release, which led to the preparation of new implants incorporating the same formulation but with an additional coating film prepared by solvent casting and comprising PCL and Lutrol F127 or PCL and Luwax EVA 3 ((poly (ethylene-co-vinyl acetate)). Implants were characterized and in vitro release profiles of acetazolamide were obtained in phosphate buffered saline (PBS) at 37 °C. The release profile of the acetazolamide from coated implant containing Luwax EVA 3 is considerably slower than what was observed in case of coated implants containing Lutrol F127, allowing a sustained release and an innovation relatively to other ocular drug delivery systems. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

27 pages, 6555 KiB  
Article
Development and Characterization of a Tacrolimus/Hydroxypropyl-β-Cyclodextrin Eye Drop
by Xurxo García-Otero, Victoria Díaz-Tomé, Rubén Varela-Fernández, Manuel Martín-Pastor, Miguel González-Barcia, José Blanco-Méndez, Cristina Mondelo-García, Maria A. Bermudez, Francisco Gonzalez, Pablo Aguiar, Anxo Fernández-Ferreiro and Francisco J. Otero-Espinar
Pharmaceutics 2021, 13(2), 149; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13020149 - 23 Jan 2021
Cited by 19 | Viewed by 3639
Abstract
Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was [...] Read more.
Uveitis is a vision inflammatory disorder with a high prevalence in developing countries. Currently, marketed treatments remain limited and reformulation is usually performed to obtain a tacrolimus eye drop as a therapeutic alternative in corticosteroid-refractory eye disease. The aim of this work was to develop a mucoadhesive, non-toxic and stable topical ophthalmic formulation that can be safely prepared in hospital pharmacy departments. Four different ophthalmic formulations were prepared based on the tacrolimus/hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complexes’ formation. Phase solubility diagrams, Nuclear Magnetic Resonance (NMR) and molecular modeling studies showed the formation of 1:1 and 1:2 tacrolimus/HPβCD inclusion complexes, being possible to obtain a 0.02% (w/v) tacrolimus concentration by using 40% (w/v) HPβCD aqueous solutions. Formulations also showed good ophthalmic properties in terms of pH, osmolality and safety. Stability studies proved these formulations to be stable for at least 3 months in refrigeration. Ex vivo bioadhesion and in vivo ocular permanence showed good mucoadhesive properties with higher ocular permanence compared to the reference pharmacy compounding used in clinical settings (t1/2 of 86.2 min for the eyedrop elaborated with 40% (w/v) HPβCD and Liquifilm® versus 46.3 min for the reference formulation). Thus, these novel eye drops present high potential as a safe alternative for uveitis treatment, as well as a versatile composition to include new drugs intended for topical ophthalmic administration. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

11 pages, 1345 KiB  
Article
Formulation and Stability of Ataluren Eye Drop Oily Solution for Aniridia
by Celia Djayet, Dominique Bremond-Gignac, Justine Touchard, Philippe-Henri Secretan, Fabrice Vidal, Matthieu P. Robert, Alejandra Daruich, Salvatore Cisternino and Joël Schlatter
Pharmaceutics 2021, 13(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010007 - 22 Dec 2020
Cited by 6 | Viewed by 5333
Abstract
Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, [...] Read more.
Congenital aniridia is a rare and severe panocular disease characterized by a complete or partial iris defect clinically detectable at birth. The most common form of aniridia occurring in around 90% of cases is caused by PAX6 haploinsufficiency. The phenotype includes ptosis, nystagmus, corneal limbal insufficiency, glaucoma, cataract, optic nerve, and foveal hypoplasia. Ataluren eye drops aim to restore ocular surface PAX6 haploinsufficiency in aniridia-related keratopathy (ARK). However, there are currently no available forms of the ophthalmic solution. The objective of this study was to assess the physicochemical and microbiological stability of ataluren 1% eye drop in preservative-free low-density polyethylene (LDPE) bottle with an innovative insert that maintains sterility after opening. Because ataluren is a strongly lipophilic compound, the formulation is complex and involves a strategy based on co-solvents in an aqueous phase or an oily formulation capable of totally dissolving the active ingredient. The visual aspect, ataluren quantification by a stability-indicating chromatographic method, and microbiological sterility were analyzed. The oily formulation in castor oil and DMSO (10%) better protects ataluren hydrolysis and oxidative degradation and permits its complete solubilization. Throughout the 60 days period, the oily solution in the LDPE bottle remained clear without any precipitation or color modification, and no drug loss and no microbial development were detected. The demonstrated physical and microbiological stability of ataluren 1% eye drop formulation at 22–25 °C might facilitate clinical research in aniridia. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

17 pages, 3211 KiB  
Article
Quantification of Drugs in Distinctly Separated Ocular Substructures of Albino and Pigmented Rats
by Anna-Kaisa Rimpelä, Michel Garneau, Katja S. Baum-Kroker, Tanja Schönberger, Frank Runge and Achim Sauer
Pharmaceutics 2020, 12(12), 1174; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12121174 - 02 Dec 2020
Cited by 7 | Viewed by 2192
Abstract
The rat is a commonly used species in ocular drug research. Detailed methods of separating rat ocular tissues have not been described in literature. To understand the intraocular drug distribution, we developed a robust method for the separation of individual anterior and posterior [...] Read more.
The rat is a commonly used species in ocular drug research. Detailed methods of separating rat ocular tissues have not been described in literature. To understand the intraocular drug distribution, we developed a robust method for the separation of individual anterior and posterior substructures of pigmented Brown Norway (BN) and albino Wistar Han (WH) rat eyes, followed by quantification of drug concentration in these substructures. A short formalin incubation, which did not interfere with drug quantification, enabled the preservation of individual tissue sections while minimizing cross-tissue contamination, as demonstrated by histological analysis. Following oral administration, we applied the tissue separation method, in order to determine the ocular concentrations of dexamethasone and levofloxacin, as well as two in-house molecules BI 113823 and BI 1026706, compounds differing in their melanin binding. The inter-individual variability in tissue partitioning coefficients (Kp) was low, demonstrating the reproducibility of the separation method. Kp values of individual tissues varied up to 100-fold in WH and up to 46,000-fold in BN rats highlighting the importance of measuring concentration directly from the ocular tissue of interest. Additionally, clear differences were observed in the BN rat tissue partitioning compared to the WH rat. Overall, the developed method enables a reliable determination of small molecule drug concentrations in ocular tissues to support ocular drug research and development. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Graphical abstract

Review

Jump to: Research

13 pages, 1908 KiB  
Review
Aqueous Prostaglandin Eye Drop Formulations
by Phatsawee Jansook and Thorsteinn Loftsson
Pharmaceutics 2022, 14(10), 2142; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14102142 - 09 Oct 2022
Cited by 6 | Viewed by 2615
Abstract
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the [...] Read more.
Glaucoma is one of the leading causes of irreversible blindness worldwide. It is characterized by progressive optic neuropathy in association with damage to the optic nerve head and, subsequently, visual loss if it is left untreated. Among the drug classes used for the long-term treatment of open-angle glaucoma, prostaglandin analogues (PGAs) are the first-line treatment and are available as marketed eye drop formulations for intraocular pressure (IOP) reduction by increasing the trabecular and uveoscleral outflow. PGAs have low aqueous solubility and are very unstable (i.e., hydrolysis) in aqueous solutions, which may hamper their ocular bioavailability and decrease their chemical stability. Additionally, treatment with PGA in conventional eye drops is associated with adverse effects, such as conjunctival hyperemia and trichiasis. It has been a very challenging for formulation scientists to develop stable aqueous eye drop formulations that increase the PGAs’ solubility and enhance their therapeutic efficacy while simultaneously lowering their ocular side effects. Here the physiochemical properties and chemical stabilities of the commercially available PGAs are reviewed, and the compositions of their eye drop formulations are discussed. Furthermore, the novel PGA formulations for glaucoma treatment are reviewed. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

22 pages, 4089 KiB  
Review
Research Progress Concerning a Novel Intraocular Lens for the Prevention of Posterior Capsular Opacification
by Yidong Zhang, Chengshou Zhang, Silong Chen, Jianghua Hu, Lifang Shen and Yibo Yu
Pharmaceutics 2022, 14(7), 1343; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14071343 - 25 Jun 2022
Cited by 8 | Viewed by 4266
Abstract
Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, [...] Read more.
Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, and intraocular lens (IOL) pitting. Therefore, finding how to prevent PCO development is the subject of active investigations. As a replacement organ, the IOL is implanted into the lens capsule after cataract surgery, but it is also associated with the occurrence of PCO. Using IOL as a medium for PCO prophylaxis is a more facile and efficient method that has demonstrated various clinical application prospects. Thus, scientists have conducted a lot of research on new intraocular lens fabrication methods, such as optimizing IOL materials and design, and IOL surface modification (including plasma/ultraviolet/ozone treatment, chemical grafting, drug loading, coating modification, and layer-by-layer self-assembly methods). This paper summarizes the research progress for different types of intraocular lenses prepared by different surface modifications, including anti-biofouling IOLs, enhanced-adhesion IOLs, micro-patterned IOLs, photothermal IOLs, photodynamic IOLs, and drug-loading IOLs. These modified intraocular lenses inhibit PCO development by reducing the residual intraoperative lens epithelial cells or by regulating the cellular behavior of lens epithelial cells. In the future, more works are needed to improve the biosecurity and therapeutic efficacy of these modified IOLs. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

22 pages, 15722 KiB  
Review
Factors Affecting Posterior Capsule Opacification in the Development of Intraocular Lens Materials
by Grace Cooksley, Joseph Lacey, Marcus K. Dymond and Susan Sandeman
Pharmaceutics 2021, 13(6), 860; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13060860 - 10 Jun 2021
Cited by 15 | Viewed by 7724
Abstract
Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule [...] Read more.
Posterior capsule opacification (PCO) is the most common complication arising from the corrective surgery used to treat cataract patients. PCO arises when lens epithelial cells (LEC) residing in the capsular bag post-surgery undergo hyper-proliferation and transdifferentiation into myofibroblasts, migrating from the posterior capsule over the visual axis of the newly implanted intraocular lens (IOL). The developmental pathways underlying PCO are yet to be fully understood and the current literature is contradictory regarding the impact of the recognised risk factors of PCO. The aim of this review is firstly to collate the known biochemical pathways that lead to PCO development, providing an up-to-date chronological overview from surgery to established PCO formation. Secondly, the risk factors of PCO are evaluated, focussing on the impact of IOLs’ properties. Finally, the latest experimental model designs used in PCO research are discussed to demonstrate the ongoing development of clinical PCO models, the efficacy of newly developed IOL technology, and potential therapeutic interventions. This review will contribute to current PCO literature by presenting an updated overview of the known developmental pathways of PCO, an evaluation of the impact of the risk factors underlying its development, and the latest experimental models used to investigate PCO. Furthermore, the review should provide developmental routes for research into the investigation of potential therapeutic interventions and improvements in IOL design in the aid of preventing PCO for new and existing patients. Full article
(This article belongs to the Special Issue Ophthalmic Drug Delivery, 2nd Edition)
Show Figures

Figure 1

Back to TopTop