Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy
Abstract
:1. Introduction
2. Glaucoma
3. Ocular Barriers
4. Current Therapies for Glaucoma
5. Constraints of Current Glaucoma Drug Delivery Treatment
5.1. Eye Drops and Eye Ointments
5.2. Trabeculectomy
5.3. Laser Treatment
5.4. Oral Medication
6. Current Pharmaceutical Interventions for the Treatment of Glaucoma
6.1. Beta-Adrenergic Blockers
6.2. PG Analogs
6.3. Alpha-Adrenergic Agonists
6.4. Carbonic Anhydrase Inhibitors
6.5. Miotic Agents
6.6. Hyperosmotic Agents
7. Natural Polymer-Based Hydrogels as Drug Delivery Vehicles for Glaucoma Therapy
7.1. Silk Fibroin
7.2. Chitosan
7.3. Alginic Acid
7.4. Pullulan
7.5. Hyaluronic Acid
7.6. Dextran
7.7. Methylcellulose
7.8. Gelatin
7.9. Collagen
8. Design of Hybrid Hydrogels for Injectable Drug Delivery in the Treatment of Glaucoma
8.1. Physicochemical, Pharmacokinetic, and Pharmacodynamic Properties of Ophthalmic Hydrogels
8.1.1. Drug Release Efficiency
8.1.2. Biocompatibility
8.1.3. Biodegradability
8.1.4. Porosity
8.1.5. Viscosity
8.1.6. Mechanical Strength
8.1.7. Swelling Properties
8.1.8. Rheology
8.1.9. Opacity and Transparency
9. Intravitreal Administration of Injectable Drug-Loaded Hydrogels to The Eye
Alternative Injection Locations
10. Pharmacokinetics of Intravitreal Hydrogel Drug Release
11. Discussion
12. Conclusions
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Polymers | Delivery System | Drug Used | Feature | Reference |
---|---|---|---|---|
Silk fibroin | Nanoparticles | TM | TM caused a sustained and prolonged reduction in IOP without adverse effects on the physiology of the eye compared to conventional free drug use. | [99] |
Hydroxyethyl chitosan | Hydrogel | Heparin | The heparin-loaded hydroxyethyl chitosan hydrogel was able to sustain and improve the reduction in the IOP after GFS for protracted periods of time. Clear inflammatory responses and results were not seen in the eye during the trial’s timeframe. | [100] |
Gelatin-g-poly(N-isopropylacrylamide) | Hydrogel | Pilocarpine | Pilocarpine-loaded gelatin hydrogels were designed by grafting with carboxylic end-capped poly(N-isopropylacrylamide) for anti-glaucoma treatment by intracameral administration. | [101] |
Poly (lactic-co-glycolic acid) (PLGA) | Nanoparticles | Dexamethasone and melatonin | A dual-loaded melatonin and dexamethasone poly(lactic-co-glycolic acid) nanoparticle system was designed as an anti-glaucoma treatment option. The in vitro release of the loaded drug from the nanoparticles revealed a supported delivery profile for the two medications, with no signs of burst discharge. | [102] |
Gellan gum/pullulan | Nanofibers, in situ gel | Fluorescein sodium | Development of a novel fluorescein delivery system that is applied topically in dry nanofibrous form and gelates in situ immediately after administration guaranteed a solid match to the eye structure by the designed nanofibers, which were molded into conforming geometries. Prolongation of the ocular drugs’ residence time was achieved | [103] |
Chtosan/hydroxyethyl cellulose | Ocular inserts | Dorzolamide | Dorzolamide-loaded ocular inserts were effective in glaucoma treatment. The ophthalmologic drug embedded in the polymeric matrix displayed a 3-h drug release efficiency, and released 75% of the loaded drug. | [104] |
Alginate–chitosan | Nanoparticles/nanogels | TM | This study proposed that loading and delivering TM onto alginate–chitosan nanoparticles may be a suitable drug delivery approach for controlled delivery of TM through the cornea | [99] |
Natural Biopolymer | Gelation | Strengths | Drawbacks | Reference |
---|---|---|---|---|
Silk fibroin | Ionic crosslinking, hydrophobic interactions | Easily modified | Low mechanical strength | [53] |
Chitosan | Chemical crosslinking, pH gelation | Simple to adjust | Low dissolvability at neutral pH | [54] |
Alginate | Chemical gelation, ionic crosslinking | Favorable mechanical properties, rapid gelation | Poor cytoadhesion | [55] |
Gelatin | Chemical crosslinking | Hydrophilic, various responses available | Susceptible to degradation, poor mechanical properties, | [94] |
Pullulan | Chemical crosslinking | Easily dissolvable | Undesirable swelling properties and mechanical properties | [77] |
Methylcellulose | Hydrophobic, chemical, physical | Easy modification of physiochemical properties | Uncontrollable degradation, poor cell adhesion, poor mechanical properties | [74,89] |
Dextran | Chemical crosslinking, physical crosslinking | Simple crosslinking, large capacity, hydrophilic, controlled drug release | Prone to causing in vivo side effects | [71,90] |
Hyaluronic acid | High temperature (specific to contact with other polymers), chemical gelation | Simple modification, natural vitreous component (ECM), bioactive | High viscosity, susceptible to degradation | [80] |
Collagen | Chemical crosslinking, high temperature | Natural ECM component, favorable cell adhesion, | Susceptible to degradation, strenuous dissolution | [85] |
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Akulo, K.A.; Adali, T.; Moyo, M.T.G.; Bodamyali, T. Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy. Polymers 2022, 14, 2359. https://doi.org/10.3390/polym14122359
Akulo KA, Adali T, Moyo MTG, Bodamyali T. Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy. Polymers. 2022; 14(12):2359. https://doi.org/10.3390/polym14122359
Chicago/Turabian StyleAkulo, Kassahun Alula, Terin Adali, Mthabisi Talent George Moyo, and Tulin Bodamyali. 2022. "Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy" Polymers 14, no. 12: 2359. https://doi.org/10.3390/polym14122359
APA StyleAkulo, K. A., Adali, T., Moyo, M. T. G., & Bodamyali, T. (2022). Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy. Polymers, 14(12), 2359. https://doi.org/10.3390/polym14122359