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Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria, 6, 95125 Catania, Italy

1. REQUIMTE, MEDTECH, Laboratory of Pharmaceutical Technology, Department of Drug Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
2. Mesosystem Investigação & Investimentos by Spinpark, Barco, 4805-017 Guimarães, Portugal

Dr. Debora Santonocito

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Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria, 6, 95125 Catania, Italy

Dr. Carmelo Puglia

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Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria, 6, 95125 Catania, Italy

New Challenges in Ocular Drug Delivery

Abstract submission deadline

closed (30 June 2023)

Manuscript submission deadline

closed (31 August 2023)

Viewed by

23433

Topic Information

Dear Colleagues,

The clinical treatment of diseases affecting the eye globe, and specifically the retina and posterior eye segment, is often hindered by the physiological protection structures and mechanisms of the organ, as well as by the unsuitable physico-chemical features of the active molecules. Intravitreal injections of drugs and monoclonal antibodies is at present the most common therapeutic procedure to reach the retinal area, however being associated to a high risk of side effects, apart than requiring the intervention of a physician. One of the ‘dream goals’ in this field still remains reaching the retinal area using a simple topically applied eye-drop formulation. Researches in the last years have progressively made available new strategies and technologies to overcome the problems that hinder an efficacious ocular drug bioavailability, leading to even more safe, easy-to-use and highly compliant therapeutic means. Controlled release as well as nanomedicine approaches, mainly based on polymeric or lipid matrices, are among the most largely explored strategies to pursue this aim. The Topic is aimed at collecting the most recent experiences from worldwide laboratories to make an update of the state-of-the-art and open new perspectives toward innovative and effective ocular therapies. In particular, studies dealing with biotech products and gene material will be welcommed, since the association of new therapeutic means with personalized treatments is ready to become the most exciting ambition for the next future of ophthalmology.

Prof. Dr. Rosario Pignatello
Dr. Hugo Almeida
Dr. Debora Santonocito
Dr. Carmelo Puglia
Topic Editors

Keywords

ophthalmology
ocular diseases
drug delivery
drug targeting
controlled drug release
ophthalmic formulations
eye drops
biopolymers
nanomedicine
nanoparticles
inserts
retina

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Journal of Nanotheranostics jnt	-	-	2020	26.8 Days	CHF 1000
Nanomaterials nanomaterials	5.3	7.4	2010	13.6 Days	CHF 2900
Pharmaceuticals pharmaceuticals	4.6	4.7	2004	14.6 Days	CHF 2900
Pharmaceutics pharmaceutics	5.4	6.9	2009	14.2 Days	CHF 2900
Journal of Functional Biomaterials jfb	4.8	5.0	2010	13.3 Days	CHF 2700

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Published Papers (13 papers)

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19 pages, 4570 KiB

Open AccessArticle

Rutin/Sulfobutylether-β-Cyclodextrin as a Promising Therapeutic Formulation for Ocular Infection

by Federica De Gaetano, Martina Pastorello, Venerando Pistarà, Antonio Rescifina, Fatima Margani, Vincenzina Barbera, Cinzia Anna Ventura and Andreana Marino

Pharmaceutics 2024, 16(2), 233; https://doi.org/10.3390/pharmaceutics16020233 - 05 Feb 2024

Viewed by 775

Abstract

Ocular pathologies present significant challenges to achieving effective therapeutic results due to various anatomical and physiological barriers. Natural products such as flavonoids, alone or in association with allopathic drugs, present many therapeutic actions including anticancer, anti-inflammatory, and antibacterial action. However, their clinical employment is challenging for scientists due to their low water solubility. In this study, we designed a liquid formulation based on rutin/sulfobutylether-β-cyclodextrin (RTN/SBE-β-CD) inclusion complex for treating ocular infections. The correct stoichiometry and the accurate binding constant were determined by employing SupraFit software (2.5.120) in the UV-vis titration experiment. A deep physical–chemical characterization of the RTN/SBE-β-CD inclusion complex was also performed; it confirmed the predominant formation of a stable complex (K_c, 9660 M⁻¹) in a 1:1 molar ratio, with high water solubility that was 20 times (2.5 mg/mL) higher than the free molecule (0.125 mg/mL), permitting the dissolution of the solid complex within 30 min. NMR studies revealed the involvement of the bicyclic flavonoid moiety in the complexation, which was also confirmed by molecular modeling studies. In vitro, the antibacterial and antibiofilm activity of the formulation was assayed against Staphylococcus aureus and Pseudomonas aeruginosa strains. The results demonstrated a significant activity of the formulation than that of the free molecules. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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27 pages, 5564 KiB

Open AccessArticle

Formulating Resveratrol and Melatonin Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Ocular Administration Using Design of Experiments

by Elide Zingale, Angela Bonaccorso, Agata Grazia D’Amico, Rosamaria Lombardo, Velia D’Agata, Jarkko Rautio and Rosario Pignatello

Pharmaceutics 2024, 16(1), 125; https://doi.org/10.3390/pharmaceutics16010125 - 18 Jan 2024

Cited by 2 | Viewed by 1172

Abstract

Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye’s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween^® 80, Tween^® 20, Solutol^® HS15, and Cremophor^® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween^® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol^® PGMC, Tween^® 80, and Transcutol^® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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16 pages, 3745 KiB

Open AccessArticle

Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material

by Susmita Bose, Chau-Minh Phan, Muhammad Rizwan, John Waylon Tse, Evelyn Yim and Lyndon Jones

Pharmaceutics 2024, 16(1), 26; https://doi.org/10.3390/pharmaceutics16010026 - 24 Dec 2023

Viewed by 3442

Abstract

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+). Methods: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlue^TM assay and the LIVE/DEAD^TM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations. Results: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels. Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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14 pages, 2423 KiB

Open AccessArticle

Celecoxib/Cyclodextrin Eye Drop Microsuspensions: Evaluation of In Vitro Cytotoxicity and Anti-VEGF Efficacy for Retinal Diseases

by Phatsawee Jansook, Hay Man Saung Hnin Soe, Rathapon Asasutjarit, Theingi Tun, Hay Marn Hnin, Phyo Darli Maw, Tanapong Watchararot and Thorsteinn Loftsson

Pharmaceutics 2023, 15(12), 2689; https://doi.org/10.3390/pharmaceutics15122689 - 28 Nov 2023

Viewed by 1118

Abstract

Celecoxib (CCB), a cyclooxygenase-2 inhibitor, is capable of reducing oxidative stress and vascular endothelial growth factor (VEGF) expression in retinal cells and has been shown to be effective in the treatment of diabetic retinopathy and age-related macular degeneration. However, the ocular bioavailability of CCB is hampered due to its very low aqueous solubility. In a previous study, we developed 0.5% (w/v) aqueous CCB eye drop microsuspensions (MS) containing randomly methylated β-cyclodextrin (RMβCD) or γ-cyclodextrin (γCD) and hyaluronic acid (HA) as ternary CCB/CD/HA nanoaggregates. Both formulations exhibited good physicochemical properties. Therefore, we further investigated their cytotoxicity and efficacy in a human retina cell line in this study. At a CCB concentration of 1000 μg/mL, both CCB/RMβCD and CCB/γCD eye drop MS showed low hemolysis activity (11.1 ± 0.3% or 4.9 ± 0.2%, respectively). They revealed no signs of causing irritation and were nontoxic to retinal pigment epithelial cells. Moreover, the CCB eye drop MS exhibited significant anti-VEGF activity by reducing VEGF mRNA and protein levels compared to CCB suspended in phosphate buffer saline. The ex vivo transscleral diffusion demonstrated that a high quantity of CCB (112.47 ± 37.27 μg/mL) from CCB/γCD eye drop MS was deposited in the porcine sclera. Our new findings suggest that CCB/CD eye drop MS could be safely delivered to the ocular tissues and demonstrate promising eye drop formulations for retinal disease treatment. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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12 pages, 3788 KiB

Open AccessArticle

A Rapid Screening Platform for Simultaneous Evaluation of Biodegradation and Therapeutic Release of an Ocular Hydrogel

by Brandon Ho, Chau-Minh Phan, Piyush Garg, Parvin Shokrollahi and Lyndon Jones

Pharmaceutics 2023, 15(11), 2625; https://doi.org/10.3390/pharmaceutics15112625 - 15 Nov 2023

Viewed by 1283

Abstract

This study attempts to address the challenge of accurately measuring the degradation of biodegradable hydrogels, which are frequently employed in drug delivery for controlled and sustained release. The traditional method utilizes a mass-loss approach, which is cumbersome and time consuming. The aim of this study was to develop an innovative screening platform using a millifluidic device coupled with automated image analysis to measure the degradation of Gelatin methacrylate (GelMA) and the subsequent release of an entrapped wetting agent, polyvinyl alcohol (PVA). Gel samples were placed within circular wells on a custom millifluidic chip and stained with a red dye for enhanced visualization. A camera module captured time-lapse images of the gels throughout their degradation. An image-analysis algorithm was used to translate the image data into degradation rates. Simultaneously, the eluate from the chip was collected to quantify the amount of GelMA degraded and PVA released at various time points. The visual method was validated by comparing it with the mass-loss approach (R = 0.91), as well as the amount of GelMA eluted (R = 0.97). The degradation of the GelMA gels was also facilitated with matrix metalloproteinases 9. Notably, as the gels degraded, there was an increase in the amount of PVA released. Overall, these results support the use of the screening platform to assess hydrogel degradation and the subsequent release of entrapped therapeutic compounds. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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15 pages, 2543 KiB

Open AccessArticle

Development of ARPE-19-Equipped Ocular Cell Model for In Vitro Investigation on Ophthalmic Formulations

by Simona Sapino, Giulia Chindamo, Elena Peira, Daniela Chirio, Federica Foglietta, Loredana Serpe, Barbara Vizio and Marina Gallarate

Pharmaceutics 2023, 15(10), 2472; https://doi.org/10.3390/pharmaceutics15102472 - 16 Oct 2023

Viewed by 655

Abstract

Repeated intravitreal (IVT) injections in the treatment of retinal diseases can lead to severe complications. Developing innovative drug delivery systems for IVT administration is crucial to prevent adverse reactions, but requires extensive investigation including the use of different preclinical models (in vitro, ex vivo and in vivo). Our previous work described an in vitro tricompartmental ocular flow cell (TOFC) simulating the anterior and posterior cavities of the human eye. Based on promising preliminary results, in this study, a collagen scaffold enriched with human retinal pigmented epithelial cells (ARPE-19) was developed and introduced into the TOFC to partially mimic the human retina. Cells were cultured under dynamic flow conditions to emulate the posterior segment of the human eye. Bevacizumab was then injected into the central compartment of the TOFC to treat ARPE-19 cells and assess its effects. The results showed an absence of cytotoxic activity and a significant reduction in VEGF fluorescent signal, underscoring the potential of this in vitro model as a platform for researching new ophthalmic formulations addressing the posterior eye segment, eventually decreasing the need for animal testing. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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15 pages, 4178 KiB

Open AccessArticle

Development and Bioactivity of Zinc Sulfate Cross-Linked Polysaccharide Delivery System of Dexamethasone Phosphate

by Natallia V. Dubashynskaya, Anton N. Bokatyi, Andrey S. Trulioff, Artem A. Rubinstein, Igor V. Kudryavtsev and Yury A. Skorik

Pharmaceutics 2023, 15(10), 2396; https://doi.org/10.3390/pharmaceutics15102396 - 28 Sep 2023

Viewed by 980

Abstract

Improving the biopharmaceutical properties of glucocorticoids (increasing local bioavailability and reducing systemic toxicity) is an important challenge. The aim of this study was to develop a dexamethasone phosphate (DexP) delivery system based on hyaluronic acid (HA) and a water-soluble cationic chitosan derivative, diethylaminoethyl chitosan (DEAECS). The DexP delivery system was a polyelectrolyte complex (PEC) resulting from interpolymer interactions between the HA polyanion and the DEAECS polycation with simultaneous incorporation of zinc ions as a cross-linking agent into the complex. The developed PECs had a hydrodynamic diameter of 244 nm and a ζ-potential of +24.4 mV; the encapsulation efficiency and DexP content were 75.6% and 45.4 μg/mg, respectively. The designed DexP delivery systems were characterized by both excellent mucoadhesion and prolonged drug release (approximately 70% of DexP was released within 10 h). In vitro experiments showed that encapsulation of DexP in polysaccharide nanocarriers did not reduce its anti-inflammatory activity compared to free DexP. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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21 pages, 6192 KiB

Open AccessArticle

Development of Osthole-Loaded Microemulsions as a Prospective Ocular Delivery System for the Treatment of Corneal Neovascularization: In Vitro and In Vivo Assessments

by Yali Zhang, Jingjing Yang, Yinjian Ji, Zhen Liang, Yuwei Wang and Junjie Zhang

Pharmaceuticals 2023, 16(10), 1342; https://doi.org/10.3390/ph16101342 - 22 Sep 2023

Viewed by 867

Abstract

Osthole (OST), a natural coumarin compound, has shown a significant inhibitory effect on corneal neovascularization (CNV). But, its effect on treating CNV is restricted by its water insolubility. To overcome this limitation, an OST-loaded microemulsion (OST-ME) was created to improve the drug’s therapeutic effect on CNV after topical administration. The OST-ME formulation comprised Capryol-90 (CP-90), Cremophor^® EL (EL-35), Transcutol-P (TSP) and water, and sodium hyaluronate (SH) was also included to increase viscosity. The OST-ME had a droplet size of 16.18 ± 0.02 nm and a low polydispersity index (0.09 ± 0.00). In vitro drug release from OST-ME fitted well to the Higuchi release kinetics model. Cytotoxicity assays demonstrated that OST-ME was not notably toxic to human corneal epithelial cells (HCECs), and the formulation had no irritation to rabbit eyes. Ocular pharmacokinetics studies showed that the areas under the concentration–time curves (AUC_0-t) in the cornea and conjunctiva were 19.74 and 63.96 μg/g*min after the administration of OST-ME, both of which were 28.2- and 102.34-fold higher than those after the administration of OST suspension (OST-Susp). Moreover, OST-ME (0.1%) presented a similar therapeutic effect to commercially available dexamethasone eye drops (0.025%) on CNV in mouse models. In conclusion, the optimized OST-ME exhibited good tolerance and enhanced 28.2- and 102.34-fold bioavailability in the cornea and conjunctiva tissues compared with suspensions in rabbit eyes. The OST-ME is a potential ocular drug delivery for anti-CNV. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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18 pages, 1897 KiB

Open AccessArticle

Discovery and Potential Utility of a Novel Non-Invasive Ocular Delivery Platform

by Weizhen (Jenny) Wang and Nonna Snider

Pharmaceutics 2023, 15(9), 2344; https://doi.org/10.3390/pharmaceutics15092344 - 19 Sep 2023

Viewed by 1086

Abstract

To this day, the use of oily eye drops and non-invasive retinal delivery remain a major challenge. Oily eye drops usually cause ocular irritation and interfere with the normal functioning of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here, the authors report a novel topical non-invasive ocular delivery platform (NIODP) through the periorbital skin for high-efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7 mg JV-MD2 (omega 3 DHA) was delivered via the NIODP and reached the retina at a Cmax of 111 µg/g and the cornea at a Cmax of 66 µg/g. The NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to the anterior segments of the NHP. The topical NIODP seems to transport drug candidates through the corneal pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery. This is especially the case for oily eye drops and retinal delivery, where the success of the treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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73 pages, 3632 KiB

Open AccessReview

Suprachoroidal Injection: A Novel Approach for Targeted Drug Delivery

by Kevin Y. Wu, Jamie K. Fujioka, Tara Gholamian, Marian Zaharia and Simon D. Tran

Pharmaceuticals 2023, 16(9), 1241; https://doi.org/10.3390/ph16091241 - 01 Sep 2023

Cited by 6 | Viewed by 3356

Abstract

Treating posterior segment and retinal diseases poses challenges due to the complex structures in the eye that act as robust barriers, limiting medication delivery and bioavailability. This necessitates frequent dosing, typically via eye drops or intravitreal injections, to manage diseases, often leading to side effects with long-term use. Suprachoroidal injection is a novel approach for targeted drug delivery to the posterior segment. The suprachoroidal space is the region between the sclera and the choroid and provides a potential route for minimally invasive medication delivery. Through a more targeted delivery to the posterior segment, this method offers advantages over other routes of administration, such as higher drug concentrations, increased bioavailability, and prolonged duration of action. Additionally, this approach minimizes the risk of corticosteroid-related adverse events such as cataracts and intraocular pressure elevation via compartmentalization. This review focuses on preclinical and clinical studies published between 2019 and 2023, highlighting the potential of suprachoroidal injection in treating a variety of posterior segment diseases. However, to fully harness its potential, more research is needed to address current challenges and limitations, such as the need for technological advancements, refinement of injection techniques, and consideration of cost and accessibility factors. Future studies exploring its use in conjunction with biotech products, gene therapies, and cell-based therapies can lead to personalized treatments that can revolutionize the field of ophthalmology. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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38 pages, 1095 KiB

Open AccessReview

Innovative Strategies for Drug Delivery to the Ocular Posterior Segment

by Andrea Gabai, Marco Zeppieri, Lucia Finocchio and Carlo Salati

Pharmaceutics 2023, 15(7), 1862; https://doi.org/10.3390/pharmaceutics15071862 - 01 Jul 2023

Cited by 4 | Viewed by 2319

Abstract

Innovative and new drug delivery systems (DDSs) have recently been developed to vehicle treatments and drugs to the ocular posterior segment and the retina. New formulations and technological developments, such as nanotechnology, novel matrices, and non-traditional treatment strategies, open new perspectives in this field. The aim of this mini-review is to highlight promising strategies reported in the current literature based on innovative routes to overcome the anatomical and physiological barriers of the vitreoretinal structures. The paper also describes the challenges in finding appropriate and pertinent treatments that provide safety and efficacy and the problems related to patient compliance, acceptability, effectiveness, and sustained drug delivery. The clinical application of these experimental approaches can help pave the way for standardizing the use of DDSs in developing enhanced treatment strategies and personalized therapeutic options for ocular pathologies. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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13 pages, 3039 KiB

Open AccessReview

by Julia Prinz, Nicola Maffulli, Matthias Fuest, Peter Walter, Frank Hildebrand and Filippo Migliorini

Pharmaceuticals 2023, 16(5), 762; https://doi.org/10.3390/ph16050762 - 18 May 2023

Cited by 2 | Viewed by 2114

Abstract

This systematic review and meta-analysis investigated whether honey-related treatment strategies improve the signs and symptoms of patients with dry eye disease (DED). In March 2023, the following databases were accessed for clinical trials investigating the efficacy of honey-related treatment strategies in DED: PubMed, Web of Science, Google Scholar, and EMBASE. The following data were extracted at baseline and at the last follow-up: Ocular Surface Disease Index, tear breakup time, Schirmer I test, and corneal staining. Data from 323 patients were retrieved (53.3% female, mean age 40.6 ± 18.1 years). The mean follow-up was 7.0 ± 4.2 weeks. All the endpoints of interest significantly improved from baseline to the last follow-up: tear breakup time (p = 0.01), Ocular Surface Disease Index (p < 0.0001), Schirmer I test (p = 0.0001), and corneal staining (p < 0.0001). No difference was found in tear breakup time (p = 0.3), Ocular Surface Disease Index (p = 0.4), Schirmer I test (p = 0.3), and corneal staining (p = 0.3) between the honey-related treatment strategies and the control groups. According to our main results, honey-related treatment strategies are effective and feasible to improve symptoms and signs of DED. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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27 pages, 4203 KiB

Open AccessArticle

Travoprost Liquid Nanocrystals: An Innovative Armamentarium for Effective Glaucoma Therapy

by Mohamed A. El-Gendy, Mai Mansour, Mona I. A. El-Assal, Rania A. H. Ishak and Nahed D. Mortada

Pharmaceutics 2023, 15(3), 954; https://doi.org/10.3390/pharmaceutics15030954 - 15 Mar 2023

Cited by 3 | Viewed by 1466

Abstract

To date, the ophthalmic application of liquid crystalline nanostructures (LCNs) has not been thoroughly reconnoitered, yet they have been extensively used. LCNs are primarily made up of glyceryl monooleate (GMO) or phytantriol as a lipid, a stabilizing agent, and a penetration enhancer (PE). For optimization, the D-optimal design was exploited. A characterization using TEM and XRPD was conducted. Optimized LCNs were loaded with the anti-glaucoma drug Travoprost (TRAVO). Ex vivo permeation across the cornea, in vivo pharmacokinetics, and pharmacodynamic studies were performed along with ocular tolerability examinations. Optimized LCNs are constituted of GMO, Tween^® 80 as a stabilizer, and either oleic acid or Captex^® 8000 as PE at 25 mg each. TRAVO-LNCs, F-1-L and F-3-L, showed particle sizes of 216.20 ± 6.12 and 129.40 ± 11.73 nm, with EE% of 85.30 ± 4.29 and 82.54 ± 7.65%, respectively, revealing the highest drug permeation parameters. The bioavailability of both attained 106.1% and 322.82%, respectively, relative to the market product TRAVATAN^®. They exhibited respective intraocular pressure reductions lasting for 48 and 72 h, compared to 36 h for TRAVATAN^®. All LCNs exhibited no evidence of ocular injury in comparison to the control eye. The findings revealed the competence of TRAVO-tailored LCNs in glaucoma treatment and suggested the potential application of a novel platform in ocular delivery. Full article

(This article belongs to the Topic New Challenges in Ocular Drug Delivery)

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Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Journal of Nanotheranostics jnt	-	-	2020	26.8 Days	CHF 1000
Nanomaterials nanomaterials	5.3	7.4	2010	13.6 Days	CHF 2900
Pharmaceuticals pharmaceuticals	4.6	4.7	2004	14.6 Days	CHF 2900
Pharmaceutics pharmaceutics	5.4	6.9	2009	14.2 Days	CHF 2900
Journal of Functional Biomaterials jfb	4.8	5.0	2010	13.3 Days	CHF 2700

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