. 2021 Sep 22;16:6497–6530. doi: 10.2147/IJN.S329831

Table 3.

Nanocarriers to Deliver Anti-Glaucoma Agents

Study	Experimental Models	Drug	Vehicle/Carriers	Production Method(s)	Results	Conclusion	Future Direction
Schnichels S, et al¹⁶⁴ 2020	DBA/2J mice model	Travoprost	Lipid DNA nanoparticles	Self-assembly of DNA amphiphiles	Travoprost nanoparticles deliver at least twice the amount of the drug at every time-point investigated compared to the pristine drug.	There is applicability of a DNA-based drug delivery system in the field of ophthalmology for the treatment of glaucoma.	In the future, a combination therapy relying on DNA-based NPs and different aptamers might be feasible.
Orasugh JT, et al¹⁶⁵ 2019	In vitro gel	Pilocarpine	Cellulose nanocrystals	Acid hydrolysis process	Have higher sustained drug release and less toxicity.	Cellulose nanocrystals have a significant effect on the gelation behavior, gel strength, and drug release kinetics of poloxamer copolymer-cellulose nanocrystals formulations.	Unspecified
Sánchez-López E, et al¹⁰² 2018	Morrison`s ocular hypertension model in Dark Agouti (DA) rats	Memantine	PLGA nanoparticles	Modification of the double emulsion solvent evaporation technique	Well tolerated in vitro (human retinoblastoma cells) and in vivo (Draize test); Reduced RGC loss in vivo.	Topical MEM-NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model.	Unspecified
Fahmy HM, et al¹⁶⁶ 2018	White albino rabbits	Latanoprost	Liposomes	Film hydration method	Reduced the IOP in glaucomatous white albino rabbits, which lasted for 8 hours.	Lip (LAT + TQ) and Lip (LAT) were the most effective tested formulations, which provided in vivo sustained drug release and showed the maximum IOP lowering effect up to 84 h as compared to other tested formulations.	None of the prepared liposome formulations succeeded in improving the glaucoma-induced oxidative stress damage.
Wang F, et al¹⁶⁷ 2018	White New Zealand rabbits	Brinzolamide	Nanoliposomes	Thin-film dispersion method	Reduced IOP in less than 1 hour, reached peak efficacy at 2 hours, and sustained release effect for 12 hours.	The HP-β-CD/BRZ loaded nanoliposomes might have a promising future as a NODDS for glaucoma treatment.	Further studies are still required to investigate the in vitro release properties of BCL and elucidate how the release profile affects the therapeutic efficacy of BCL.
Tan G, et al⁴² 2017	New Zealand albino rabbits	Timolol maleate	Chitosan coated liposomes	Ammonium sulfate gradient coupled with a pH-gradient	Significantly reduced the IOP.	CHL is a potentially useful carrier for ocular drug delivery, which could improve the efficacy of TM.	The formulation reported here will be the subject of future studies aimed at improving its clinical use.
Rathod LV, et al¹⁶⁸ 2017	Goat eyes and albino rabbits	Acetazolamide	Nanoparticles	Solvent displacement method	Displayed better permeability and flow across corneal tissue in vitro.	The nanoparticles impregnated ocular inserts can act as potential platform for delivering drug to posterior segment of eye not only for glaucoma but also for other eye diseases.	Unspecified
Ikuta Y, et al¹⁶⁹ 2017	Male Sprague-Dawley rats	Brinzolamide	Nanoparticles	Reprecipitation method	Increases the eye penetration rate and resulted in high drug efficacy.	The nano-eye-drops may have applications as a next-generation ophthalmic treatment.	Unspecified
Kouchak M, et al¹⁷⁰ 2016	Albino rabbits	Dorzolamide hydrochloride	Nanoliposomes	Reverse-phase evaporation vesicle method	Had greater IOP lowering activity and more prolonged effects.	It could be a candidate for the treatment of ocular hypertension.	Assay of DRZ in aqueous humor following drug instillation into rabbit eye should be done before clinical trials as well.
Bravo-Osuna I, et al⁹⁹ 2016	New Zealand white rabbits	Acetazolamide	Dendrimers	Hydrosilylation of Boc-protected allylamine and followed by deprotection with HCl	Demonstrated rapid (1 hour post-instillation) and sustained (up to 7 hours) hypotensive effect, reaching a peak 22.6% IOP reduction in normotensive rabbit eyes.	Carbosilane dendrimers can be used in a safe range of concentrations to enhance the bioavailability of drugs topically administered in the eye.	Unspecified
Yu S, et al¹⁷¹ 2015	New Zealand rabbits	Timolol maleate	Liposome	pH-gradient method	Reduced the IOP and the effective time was significantly longer.	Liposome incorporated ion sensitivity in situ gels has a potential ability for ophthalmic delivery.	Future work will research the pathway and mechanism of the cellular uptake of TM L-ISG.
Rodriguez-Aller M, et al⁹⁸ 2015	New Zealand rabbits	Latanoprost	Cyclodextrins	Unspecified	Improved solubility and stability in vitro. In vivo evaluation of ocular tolerability revealed that ocular irritation was 15.5% with the commercially marketed formulation of latanoprost and 9.5% with the latanoprost-propylamino-ß-CD formulation.	The latanoprost-propylamino-β-CD formulation was demonstrated to successfully address the main stability, solubility, and tolerance limitations of topical ocular latanoprost therapy for glaucoma.	Unspecified
Wong TT, et al⁹⁷ 2014	Human	Latanoprost	Nanoliposome	Gradient method	Good tolerance with no evident safety issues or adverse events.	This study provided the evidence and support for further clinical studies of liposomal latanoprost in the treatment of glaucoma.	The authors were planning additional controlled clinical studies.
Singh J, et al¹⁷² 2014	Rabbits model	Acetazolamide	Polymeric nanoparticles	Nanoprecipitation method	Sustained release effects and increased transcorneal permeation in vivo.	NP-ISG5 may offer intensive management of glaucoma via higher permeation, prolonged precorneal residence time and sustained drug release along with higher in vitro efficacy, safety and patient compliance.	These systems are emerging as vehicles for the treatment of diseases of posterior portion of eye which is not possible by topical delivery through conventional systems.
Tuomela A, et al¹⁷³ 2014	Wistar rats	Brinzolamide	Nanocrystal	Top-down wet milling technique	The IOP lowering effect was investigated using a modern rat ocular hypertensive model and elevated IOP reduction was seen in vivo with all the formulations. The reduction achieved in experimentally elevated IOP was comparable to that obtained with a commercial product.	Various BRA nanocrystal formulations which all showed advantageous dissolution and absorption behavior were successfully formulated.	Unspecified
Mishra V, et al¹⁷⁴ 2014	New Zealand albino rabbits	Acetazolamide	Poly(propylene imine) dendrimer nanoarchitectures	Unspecified	The sustained and prolonged reduction in IOP suggested that drug entrapped in dendrimers can be used for higher retention in ocular cul-de sac.	The PPI dendrimer based formulation seems to enhance the ocular drug residence time and exhibits better intraocular pressure lowering effect for glaucoma treatment	Unspecified
Jung HJ, et al¹⁷⁵ 2013	Beagle dogs	Timolol	Nanoparticles of PGT (propoxylated glyceryl triacylate)	Thermal polymerization of a mixture of timolol base and PGT.	Sustained release of the timolol.	Preliminary in vivo animal studies demonstrate safety and efficacy of the particle loaded lenses treating glaucoma.	Further in vivo safety and pharmacokinetics and pharmacodynamics tests particularly with lenses in which particles are loaded prior to lens fabrication are necessary to evaluate the potential of the proposed approach for glaucoma therapy.
Wu W, et al¹⁷⁶ 2013	New Zealand rabbits	Brinzolamide	Liquid crystalline nanoparticles	Modified emulsification method	Had advantages such as lower doses but maintaining the effectiveness, better ocular bioavailability, and patient compliance compared with Azopt^®.	BLZ LCNPs would be a promising delivery system used for the treatment of glaucoma	Unspecified
Natarajan JV, et al¹⁷⁷ 2012	New Zealand White rabbits	Latanoprost	Egg PC liposomes	Hydration method	A greater sustained IOP lowering effect compared with daily administration of topical latanoprost beyond 90 days.	A single injection of latanoprost-loaded Egg PC liposomes can lower the IOP for up to 90 days, with a greater IOP lowering effect than daily topical administration of latanoprost.	Further detailed studies on the pharmacodynamics of these liposomes within the ocular tissues will determine its future potential clinical application.