Nanoparticles in Ocular Drug Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 32728

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Special Issue Editors

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
Interests: prolonged release; colloidal dispersions; solid lipid nanoparticles; nanostructured lipid carriers; pharmaceutical industry; medical devices; cosmetic products
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. UCIBIO, REQUIMTE, Laboratory of Pharmaceutical Technology/Centre of Research in Pharmaceutical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
2. Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal
3. FP-I3ID (Instituto de Investigação, Inovação e Desenvolvimento), FP-BHS (Biomedical and Health Sciences Research Unit), Faculty of Health Sciences, University Fernando Pessoa, 4249-004 Porto, Portugal
Interests: nasal and cutaneous drug delivery; nose-to-brain delivery; lipid nanoparticles; biopharmaceuticals; biological medicines; advanced therapy medicinal products (ATMPs)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Conventional ophthalmic formulations lack a prolonged drug release effect and mucoadhesive properties, decreasing their residence time in the precorneal area and, therefore, in drug penetration across ocular tissues, presenting a low bioavailability with a consequent reduction in the therapeutic efficacy. These limitations are related to the physiological mechanisms of the eye, for example, the diluting effect of formulations exerted by the tear fluid, constant turnover of the tear fluid, blink reflex, limited capacity of the conjunctival sac, and drainage of formulations applied by gravity.

To increase the residence time of formulations on the surface of ocular tissues and increase their ability to penetrate these tissues, different strategies can be used, namely, the use of viscosifying agents, mucoadhesive polymers, stimuli-responsive polymers, microparticles, and colloidal carriers (e.g., micelles, liposomes, nanosuspensions, nanoemulsions, polymeric, and lipid nanoparticles). This Special Issue combines the latest research and review works reporting the use of nanoparticles in ophthalmic formulations to increase their bioavailability and improve the therapeutic efficacy of ophthalmic formulations.

Dr. Hugo Almeida
Dr. Ana Catarina Silva
Guest Editors

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Keywords

  • ocular drug delivery
  • ophthalmic formulations
  • eye drops
  • prolonged release
  • colloidal dispersions
  • solid lipid nanoparticles

Published Papers (13 papers)

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Editorial

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2 pages, 183 KiB  
Editorial
Nanoparticles in Ocular Drug Delivery Systems
by Hugo Almeida and Ana Catarina Silva
Pharmaceutics 2023, 15(6), 1675; https://doi.org/10.3390/pharmaceutics15061675 - 08 Jun 2023
Cited by 2 | Viewed by 948
Abstract
Conventional ophthalmic formulations lack a prolonged drug release effect and mucoadhesive properties, decreasing their residence time in the precorneal area and, therefore, in drug penetration across ocular tissues, presenting low bioavailability with a consequent reduction in therapeutic efficacy [...] Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)

Research

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22 pages, 10487 KiB  
Article
Development of Triamcinolone Acetonide Nanocrystals for Ocular Administration
by María Lina Formica, Hamoudi Ghassan Awde Alfonso, Alejandro Javier Paredes, María Elisa Melian, Nahuel Matías Camacho, Ricardo Faccio, Luis Ignacio Tártara and Santiago Daniel Palma
Pharmaceutics 2023, 15(2), 683; https://doi.org/10.3390/pharmaceutics15020683 - 17 Feb 2023
Cited by 4 | Viewed by 2054
Abstract
Triamcinolone acetonide (TA) is a powerful anti-inflammatory drug used in the treatment of inflammatory ocular disorders; however, its poor aqueous solubility and ocular anatomical barriers hinder optimal treatment. The aim of this work was to obtain triamcinolone acetonide nanocrystals (TA-NC) to improve ocular [...] Read more.
Triamcinolone acetonide (TA) is a powerful anti-inflammatory drug used in the treatment of inflammatory ocular disorders; however, its poor aqueous solubility and ocular anatomical barriers hinder optimal treatment. The aim of this work was to obtain triamcinolone acetonide nanocrystals (TA-NC) to improve ocular corticosteroid therapy. Self-dispersible TA-NC were prepared by the bead milling technique followed by spray-drying, exhaustively characterized and then evaluated in vivo in an ocular model of endotoxin-induced uveitis (EIU). Self-dispersible TA-NC presented an average particle size of 257 ± 30 nm, a narrow size distribution and a zeta potential of −25 ± 3 mV, which remained unchanged for 120 days under storage conditions at 25 °C. In addition, SEM studies of the TA-NC showed uniform and spherical morphology, and FTIR and XRDP analyses indicated no apparent chemical and crystallinity changes. The subconjunctival administration of TA-NC in albino male white rabbits showed no clinical signs of ocular damage. In vivo studies proved that treatment with self-dispersible TA-NC alleviated the inflammatory response in the anterior chamber and iris in EUI rabbit eyes. Dispersible TA-NC are a promising approach to obtaining a novel nanometric TA formulation for ocular disorders. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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22 pages, 4589 KiB  
Article
Design, Characterization and Pharmacokinetic–Pharmacodynamic Evaluation of Poloxamer and Kappa-Carrageenan-Based Dual-Responsive In Situ Gel of Nebivolol for Treatment of Open-Angle Glaucoma
by Pradeep Singh Rawat, Punna Rao Ravi, Shahid Iqbal Mir, Mohammed Shareef Khan, Himanshu Kathuria, Prasanna Katnapally and Upendra Bhatnagar
Pharmaceutics 2023, 15(2), 405; https://doi.org/10.3390/pharmaceutics15020405 - 25 Jan 2023
Cited by 10 | Viewed by 1561
Abstract
This study developed a dual-responsive in situ gel of nebivolol (NEB), a selective β-adrenergic antagonist. The gel could achieve sustained concentrations in the aqueous humor to effectively treat glaucoma. The gel was prepared using a combination of poloxamers (Poloxamer-407 (P407) and Poloxamer-188 (P188)) [...] Read more.
This study developed a dual-responsive in situ gel of nebivolol (NEB), a selective β-adrenergic antagonist. The gel could achieve sustained concentrations in the aqueous humor to effectively treat glaucoma. The gel was prepared using a combination of poloxamers (Poloxamer-407 (P407) and Poloxamer-188 (P188)) and kappa-carrageenan (κCRG) as thermo-responsive and ion-sensitive polymers, respectively. Box–Behnken design (BBD) was used to optimize the effect of three critical formulation factors (concentration of P407, P188 and κCRG) on two critical response variables (sol-to-gel transition temperature of 33–35 °C and minimum solution state viscosity) of the in situ gel. A desirability function was employed to find the optimal concentrations of P407, P188 and κCRG that yielded a gel with the desired sol-to-gel transition temperature and solution state viscosity. An NEB-loaded gel was prepared using the optimized conditions and evaluated for in vitro drug release properties and ex vivo ocular irritation studies. Furthermore, ocular pharmacokinetic and pharmacodynamics studies were conducted in rabbits for the optimized formulation. The optimized NEB-loaded gel containing P407, P188 and κCRG had a sol-to-gel transition temperature of 34 °C and exhibited minimum viscosity (212 ± 2 cP at 25 °C). The optimized NEB-loaded gel sustained drug release with 86% drug release at the end of 24 h. The optimized formulation was well tolerated in the eye. Ocular pharmacokinetic studies revealed that the optimized in situ gel resulted in higher concentrations of NEB in aqueous humor compared to the NEB suspension. The aqueous humor Cmax of the optimized in situ gel (35.14 ± 2.25 ng/mL) was 1.2 fold higher than that of the NEB suspension (28.2 ± 3.1 ng/mL), while the AUC0–∞ of the optimized in situ gel (381.8 ± 18.32 ng/mL*h) was 2 fold higher than that of the NEB suspension (194.9 ± 12.17 ng/mL*h). The systemic exposure of NEB was significantly reduced for the optimized in situ gel, with a 2.7-fold reduction in the plasma Cmax and a 4.1-fold reduction in the plasma AUC0–∞ compared with the NEB suspension. The optimized gel produced a higher and sustained reduction in the intra-ocular pressure compared with the NEB suspension. The optimized gel was more effective in treating glaucoma than the NEB suspension due to its mucoadhesive properties, sustained drug release and reduced drug loss. Lower systemic exposure of the optimized gel indicates that the systemic side effects can be significantly reduced compared to the NEB suspension, particularly in the long-term management of glaucoma. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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14 pages, 1378 KiB  
Article
Cannabidiol Loaded Topical Ophthalmic Nanoemulsion Lowers Intraocular Pressure in Normotensive Dutch-Belted Rabbits
by Samir Senapati, Ahmed Adel Ali Youssef, Corinne Sweeney, Chuntian Cai, Narendar Dudhipala and Soumyajit Majumdar
Pharmaceutics 2022, 14(12), 2585; https://doi.org/10.3390/pharmaceutics14122585 - 24 Nov 2022
Cited by 8 | Viewed by 1697
Abstract
Cannabidiol (CBD) is the major non-psychoactive and most widely studied of the cannabinoid constituents and has great therapeutic potential in a variety of diseases. However, contradictory reports in the literature with respect to CBD’s effect on intraocular pressure (IOP) have raised concerns and [...] Read more.
Cannabidiol (CBD) is the major non-psychoactive and most widely studied of the cannabinoid constituents and has great therapeutic potential in a variety of diseases. However, contradictory reports in the literature with respect to CBD’s effect on intraocular pressure (IOP) have raised concerns and halted research exploring its use in ocular therapeutics. Therefore, the current investigation aimed to further evaluate CBD’s impact on the IOP in the rabbit model. CBD nanoemulsions, containing Carbopol® 940 NF as a mucoadhesive agent (CBD-NEC), were prepared using hot-homogenization followed by probe sonication. The stability of the formulations post-moist-heat sterilization, in terms of physical and chemical characteristics, was studied for three different storage conditions. The effect of the formulation on the intraocular pressure (IOP) profile in normotensive Dutch Belted male rabbits was then examined. The lead CBD-NEC formulation (1% w/v CBD) exhibited a globule size of 259 ± 2.0 nm, 0.27 ± 0.01 PDI, and 23.2 ± 0.4 cP viscosity, and was physically and chemically stable for one month (last time point tested) at 4 °C, 25 °C, and 40 °C. CBD-NEC significantly lowered the IOP in the treated eyes for up to 360 min, with a peak drop in IOP of 4.5 mmHg observed at the 150 min time point, post-topical application. The IOP of the contralateral eye (untreated) was also observed to be lowered significantly, but the effect lasted up to the 180 min time point only. Overall, topically administered CBD, formulated in a mucoadhesive nanoemulsion formulation, reduced the IOP in the animal model studied. The results support further exploration of CBD as a therapeutic option for various inflammation-based ocular diseases. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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21 pages, 4562 KiB  
Article
Enhanced Ocular Anti-Aspergillus Activity of Tolnaftate Employing Novel Cosolvent-Modified Spanlastics: Formulation, Statistical Optimization, Kill Kinetics, Ex Vivo Trans-Corneal Permeation, In Vivo Histopathological and Susceptibility Study
by Diana Aziz, Sally A. Mohamed, Saadia Tayel and Amal Makhlouf
Pharmaceutics 2022, 14(8), 1746; https://doi.org/10.3390/pharmaceutics14081746 - 22 Aug 2022
Cited by 8 | Viewed by 1765
Abstract
Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at [...] Read more.
Tolnaftate (TOL) is a thiocarbamate fungicidal drug used topically in the form of creams and ointments. No ocular formulations of TOL are available for fungal keratitis (FK) treatment due to its poor water solubility and unique ocular barriers. Therefore, this study aimed at developing novel modified spanlastics by modulating spanlastics composition using different glycols for enhancing TOL ocular delivery. To achieve this goal, TOL basic spanlastics were prepared by ethanol injection method using a full 32 factorial design. By applying the desirability function, the optimal formula (BS6) was selected and used as a nucleus for preparing and optimizing TOL-cosolvent spanlastics according to the full 31.21 factorial design. The optimal formula (MS6) was prepared using 30% propylene glycol and showed entrapment efficiency percent (EE%) of 66.10 ± 0.57%, particle size (PS) of 231.20 ± 0.141 nm, and zeta potential (ZP) of −32.15 ± 0.07 mV. MS6 was compared to BS6 and both nanovesicles significantly increased the corneal permeation potential of TOL than drug suspension. Additionally, in vivo histopathological experiment was accomplished and confirmed the tolerability of MS6 for ocular use. The fungal susceptibility testing using Aspergillus niger confirmed that MS6 displayed more durable growth inhibition than drug suspension. Therefore, MS6 can be a promising option for enhanced TOL ocular delivery. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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17 pages, 3183 KiB  
Article
Photodisruption of the Inner Limiting Membrane: Exploring ICG Loaded Nanoparticles as Photosensitizers
by Kaat De Clerck, Geraldine Accou, Félix Sauvage, Kevin Braeckmans, Stefaan C. De Smedt, Katrien Remaut and Karen Peynshaert
Pharmaceutics 2022, 14(8), 1716; https://doi.org/10.3390/pharmaceutics14081716 - 17 Aug 2022
Cited by 6 | Viewed by 1818
Abstract
The inner limiting membrane (ILM) represents a major bottleneck hampering efficient drug delivery to the retina after intravitreal injection. To overcome this barrier, we intend to perforate the ILM by use of a light-based approach which relies on the creation of vapor nanobubbles [...] Read more.
The inner limiting membrane (ILM) represents a major bottleneck hampering efficient drug delivery to the retina after intravitreal injection. To overcome this barrier, we intend to perforate the ILM by use of a light-based approach which relies on the creation of vapor nanobubbles (VNBs) when irradiating photosensitizers with high intensity laser pulses. Upon collapse of these VNBs, mechanical effects can disrupt biological structures. As a photosensitizer, we explore indocyanine green (ICG) loaded nanoparticles (NPs) specifically designed for our application. In light of this, ICG liposomes and PLGA ICG NPs were characterized in terms of physicochemical properties, ICG incorporation and VNB formation. ICG liposomes were found to encapsulate significantly higher amounts of ICG compared to PLGA ICG NPs which is reflected in their VNB creating capacity. Since only ICG liposomes were able to induce VNB generation, this class of NPs was further investigated on retinal explants. Here, application of ICG liposomes followed by laser treatment resulted in subtle disruption effects at the ILM where zones of fully ablated ILM were alternated by intact regions. As the interaction between the ICG liposomes and ILM might be insufficient, active targeting strategies or other NP designs might improve the concept to a further extent. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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18 pages, 7288 KiB  
Article
Linoleic Acid-Based Transferosomes for Topical Ocular Delivery of Cyclosporine A
by Onyinye Uwaezuoke, Lisa C. Du Toit, Pradeep Kumar, Naseer Ally and Yahya E. Choonara
Pharmaceutics 2022, 14(8), 1695; https://doi.org/10.3390/pharmaceutics14081695 - 15 Aug 2022
Cited by 8 | Viewed by 2609
Abstract
Delivering high-molecular-weight hydrophobic peptides, such as cyclosporine A, across the corneal epithelium remains a challenge that is complicated by other physio-anatomical ocular structures that limit the ocular bioavailability of such peptides. Transferosomes have previously been used to improve transdermal permeability, and have the [...] Read more.
Delivering high-molecular-weight hydrophobic peptides, such as cyclosporine A, across the corneal epithelium remains a challenge that is complicated by other physio-anatomical ocular structures that limit the ocular bioavailability of such peptides. Transferosomes have previously been used to improve transdermal permeability, and have the potential for improving the ocular corneal permeability of applicable drugs. In this study, transferosomes for the potential ocular delivery of cyclosporine A were investigated. Linoleic acid was evaluated for its effect on the stability of the transferosomes and was substituted for a portion of the cholesterol in the vesicles. Additionally, Span® 80 and Tween® 80 were evaluated for their effect on transferosome flexibility and toxicity to ocular cells as edge activators. Attenuated Total Reflectance–Fourier Transform Infrared spectroscopy (ATF-FTIR), differential scanning calorimetry (DSC), and dynamic light scattering (DLS) were used to evaluate the physicochemical parameters of the blank and the cyclosporine A-loaded transferosomes. Cyclosporine A release and corneal permeability were studied in vitro and in a New Zealand albino rabbit corneal model, respectively. The linoleic acid contributed to improved stability and the nano-size of the transferosomes. The Tween®-based formulation was preferred on the basis of a more favorable toxicity profile, as the difference in their corneal permeability was not significant. There was an initial burst release of cyclosporine A in the first 24 h that plateaued over one week. The Tween®-based formulation had a flux of 0.78 µg/cm2/h. The prepared transferosomes demonstrated biocompatibility in the ocular cell line, adequately encapsulated cyclosporine A, ensured the corneal permeability of the enclosed drug, and were stable over the period of investigation of 4 months at −20 °C. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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15 pages, 5655 KiB  
Article
Ciprofloxacin-Loaded Zein/Hyaluronic Acid Nanoparticles for Ocular Mucosa Delivery
by Telma A. Jacinto, Breno Oliveira, Sónia P. Miguel, Maximiano P. Ribeiro and Paula Coutinho
Pharmaceutics 2022, 14(8), 1557; https://doi.org/10.3390/pharmaceutics14081557 - 27 Jul 2022
Cited by 13 | Viewed by 2888
Abstract
Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite [...] Read more.
Bacterial conjunctivitis is a worldwide problem that, if untreated, can lead to severe complications, such as visual impairment and blindness. Topical administration of ciprofloxacin is one of the most common treatments for this infection; however, topical therapeutic delivery to the eye is quite challenging. To tackle this, nanomedicine presents several advantages compared to conventional ophthalmic dosage forms. Herein, the flash nanoprecipitation technique was applied to produce zein and hyaluronic acid nanoparticles loaded with ciprofloxacin (ZeinCPX_HA NPs). ZeinCPX_HA NPs exhibited a hydrodynamic diameter of <200 nm and polydispersity index of <0.3, suitable for ocular drug delivery. In addition, the freeze-drying of the nanoparticles was achieved by using mannitol as a cryoprotectant, allowing their resuspension in water without modifying the physicochemical properties. Moreover, the biocompatibility of nanoparticles was confirmed by in vitro assays. Furthermore, a high encapsulation efficiency was achieved, and a release profile with an initial burst was followed by a prolonged release of ciprofloxacin up to 24 h. Overall, the obtained results suggest ZeinCPX_HA NPs as an alternative to the common topical dosage forms available on the market to treat conjunctivitis. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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16 pages, 1528 KiB  
Article
Physicochemical and Stability Evaluation of Topical Niosomal Encapsulating Fosinopril/γ-Cyclodextrin Complex for Ocular Delivery
by Hay Marn Hnin, Einar Stefánsson, Thorsteinn Loftsson, Rathapon Asasutjarit, Dusadee Charnvanich and Phatsawee Jansook
Pharmaceutics 2022, 14(6), 1147; https://doi.org/10.3390/pharmaceutics14061147 - 27 May 2022
Cited by 14 | Viewed by 2508
Abstract
This study aimed to develop a chemically stable niosomal eye drop containing fosinopril (FOS) for lowering intraocular pressure. The effects of cyclodextrin (CD), surfactant types and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle [...] Read more.
This study aimed to develop a chemically stable niosomal eye drop containing fosinopril (FOS) for lowering intraocular pressure. The effects of cyclodextrin (CD), surfactant types and membrane stabilizer/charged inducers on physiochemical and chemical properties of niosome were evaluated. The pH value, average particle size, size distribution and zeta potentials were within the acceptable range. All niosomal formulations were shown to be slightly hypertonic with low viscosity. Span® 60/dicetyl phosphate niosomes in the presence and absence of γCD were selected as the optimum formulations according to their high %entrapment efficiency and negative zeta potential values as well as controlled release profile. According to ex vivo permeation study, the obtained lowest flux and apparent permeability coefficient values confirmed that FOS/γCD complex was encapsulated within the inner aqueous core of niosome and could be able to protect FOS from its hydrolytic degradation. The in vitro cytotoxicity revealed that niosome entrapped FOS or FOS/γCD formulations were moderate irritation to the eyes. Furthermore, FOS-loaded niosomal preparations exhibited good physical and chemical stabilities especially of those in the presence of γCD, for at least three months under the storage condition of 2–8 °C. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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Review

Jump to: Editorial, Research

18 pages, 4597 KiB  
Review
Recent Progress in Chitosan-Based Nanomedicine for Its Ocular Application in Glaucoma
by Hassan A. Albarqi, Anuj Garg, Mohammad Zaki Ahmad, Abdulsalam A. Alqahtani, Ismail A. Walbi and Javed Ahmad
Pharmaceutics 2023, 15(2), 681; https://doi.org/10.3390/pharmaceutics15020681 - 17 Feb 2023
Cited by 5 | Viewed by 2102
Abstract
Glaucoma is a degenerative, chronic ocular disease that causes irreversible vision loss. The major symptom of glaucoma is high intraocular pressure, which happens when the flow of aqueous humor between the front and back of the eye is blocked. Glaucoma therapy is challenging [...] Read more.
Glaucoma is a degenerative, chronic ocular disease that causes irreversible vision loss. The major symptom of glaucoma is high intraocular pressure, which happens when the flow of aqueous humor between the front and back of the eye is blocked. Glaucoma therapy is challenging because of the low bioavailability of drugs from conventional ocular drug delivery systems such as eye drops, ointments, and gels. The low bioavailability of antiglaucoma agents could be due to the precorneal and corneal barriers as well as the low biopharmaceutical attributes of the drugs. These limitations can be overcome by employing nanoparticulate drug delivery systems. Over the last decade, there has been a lot of interest in chitosan-based nanoparticulate systems to overcome the limitations (such as poor residence time, low corneal permeability, etc.) associated with conventional ocular pharmaceutical products. Therefore, the main aim of the present manuscript is to review the recent research work involving the chitosan-based nanoparticulate system to treat glaucoma. It discusses the significance of the chitosan-based nanoparticulate system, which provides mucoadhesion to improve the residence time of drugs and their ocular bioavailability. Furthermore, different types of chitosan-based nanoparticulate systems are also discussed, namely nanoparticles of chitosan core only, nanoparticles coated with chitosan, and hybrid nanoparticles of chitosan. The manuscript also provides a critical analysis of contemporary research related to the impact of this chitosan-based nanomedicine on the corneal permeability, ocular bioavailability, and therapeutic performance of loaded antiglaucoma agents. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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40 pages, 4538 KiB  
Review
Ocular Delivery of Therapeutic Proteins: A Review
by Divyesh H. Shastri, Ana Catarina Silva and Hugo Almeida
Pharmaceutics 2023, 15(1), 205; https://doi.org/10.3390/pharmaceutics15010205 - 06 Jan 2023
Cited by 12 | Viewed by 4259
Abstract
Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment [...] Read more.
Therapeutic proteins, including monoclonal antibodies, single chain variable fragment (ScFv), crystallizable fragment (Fc), and fragment antigen binding (Fab), have accounted for one-third of all drugs on the world market. In particular, these medicines have been widely used in ocular therapies in the treatment of various diseases, such as age-related macular degeneration, corneal neovascularization, diabetic retinopathy, and retinal vein occlusion. However, the formulation of these biomacromolecules is challenging due to their high molecular weight, complex structure, instability, short half-life, enzymatic degradation, and immunogenicity, which leads to the failure of therapies. Various efforts have been made to overcome the ocular barriers, providing effective delivery of therapeutic proteins, such as altering the protein structure or including it in new delivery systems. These strategies are not only cost-effective and beneficial to patients but have also been shown to allow for fewer drug side effects. In this review, we discuss several factors that affect the design of formulations and the delivery of therapeutic proteins to ocular tissues, such as the use of injectable micro/nanocarriers, hydrogels, implants, iontophoresis, cell-based therapy, and combination techniques. In addition, other approaches are briefly discussed, related to the structural modification of these proteins, improving their bioavailability in the posterior segments of the eye without affecting their stability. Future research should be conducted toward the development of more effective, stable, noninvasive, and cost-effective formulations for the ocular delivery of therapeutic proteins. In addition, more insights into preclinical to clinical translation are needed. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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17 pages, 2121 KiB  
Review
Bioprinted Membranes for Corneal Tissue Engineering: A Review
by Amin Orash Mahmoud Salehi, Saeed Heidari-Keshel, Seyed Ali Poursamar, Ali Zarrabi, Farshid Sefat, Narsimha Mamidi, Mahmoud Jabbarvand Behrouz and Mohammad Rafienia
Pharmaceutics 2022, 14(12), 2797; https://doi.org/10.3390/pharmaceutics14122797 - 14 Dec 2022
Cited by 8 | Viewed by 2874
Abstract
Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection [...] Read more.
Corneal transplantation is considered a convenient strategy for various types of corneal disease needs. Even though it has been applied as a suitable solution for most corneal disorders, patients still face several issues due to a lack of healthy donor corneas, and rejection is another unknown risk of corneal transplant tissue. Corneal tissue engineering (CTE) has gained significant consideration as an efficient approach to developing tissue-engineered scaffolds for corneal healing and regeneration. Several approaches are tested to develop a substrate with equal transmittance and mechanical properties to improve the regeneration of cornea tissue. In this regard, bioprinted scaffolds have recently received sufficient attention in simulating corneal structure, owing to their spectacular spatial control which produces a three-cell-loaded-dimensional corneal structure. In this review, the anatomy and function of different layers of corneal tissue are highlighted, and then the potential of the 3D bioprinting technique for promoting corneal regeneration is also discussed. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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30 pages, 5885 KiB  
Review
Fluorescent Nanosystems for Drug Tracking and Theranostics: Recent Applications in the Ocular Field
by Elide Zingale, Alessia Romeo, Salvatore Rizzo, Cinzia Cimino, Angela Bonaccorso, Claudia Carbone, Teresa Musumeci and Rosario Pignatello
Pharmaceutics 2022, 14(5), 955; https://doi.org/10.3390/pharmaceutics14050955 - 28 Apr 2022
Cited by 9 | Viewed by 2678
Abstract
The greatest challenge associated with topical drug delivery for the treatment of diseases affecting the posterior segment of the eye is to overcome the poor bioavailability of the carried molecules. Nanomedicine offers the possibility to overcome obstacles related to physiological mechanisms and ocular [...] Read more.
The greatest challenge associated with topical drug delivery for the treatment of diseases affecting the posterior segment of the eye is to overcome the poor bioavailability of the carried molecules. Nanomedicine offers the possibility to overcome obstacles related to physiological mechanisms and ocular barriers by exploiting different ocular routes. Functionalization of nanosystems by fluorescent probes could be a useful strategy to understand the pathway taken by nanocarriers into the ocular globe and to improve the desired targeting accuracy. The application of fluorescence to decorate nanocarrier surfaces or the encapsulation of fluorophore molecules makes the nanosystems a light probe useful in the landscape of diagnostics and theranostics. In this review, a state of the art on ocular routes of administration is reported, with a focus on pathways undertaken after topical application. Numerous studies are reported in the first section, confirming that the use of fluorescent within nanoparticles is already spread for tracking and biodistribution studies. The first section presents fluorescent molecules used for tracking nanosystems’ cellular internalization and permeation of ocular tissues; discussions on the classification of nanosystems according to their nature (lipid-based, polymer-based, metallic-based and protein-based) follows. The following sections are dedicated to diagnostic and theranostic uses, respectively, which represent an innovation in the ocular field obtained by combining dual goals in a single administration system. For its great potential, this application of fluorescent nanoparticles would experience a great development in the near future. Finally, a brief overview is dedicated to the use of fluorescent markers in clinical trials and the market in the ocular field. Full article
(This article belongs to the Special Issue Nanoparticles in Ocular Drug Delivery Systems)
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