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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 38  

Review Article 

Advances in Ocular Drug Delivery System for Glaucoma Management – A 

Comprehensive Review  

Raju Maski1, Jitendra Banweer2, Megha Mishra3, Praveen Tahilani3, Gaurav Goyanar4 

From, 1M-Pharma (Pharmaceutics), 2Sagar Institute of Research Technology & Science Pharmacy,Bhopal (M.P.), 3Associate 

Professor, SIRTS Pharmacy College, Bhopal (M.P.), 4Department of Pharmaceutical Science, SAGE University, Indore M.P. 

Correspondence to: Raju Maski, M-Pharma (Pharmaceutics), Sagar Institute of Research Technology & Science Pharmacy, Bhopal 

(M.P.). Email: tahilanipraveen@gmail.com 

ABSTRACT 

In today’s world delivery of ophthalmic drugs remains challenging despite easy accessibility via the ocular surface. Eye drops are 

easy and most widely used for drug delivery for treating ocular infections, particularly involving the internal segment having an 

additional benefit of avoiding first-pass metabolism there while passing through the systemic circulation. The challenges of drug 

administration through traditional methods involve improper patient education for drug installation techniques, compliance, 

adherence, and persistence. Different dynam ic and static ocular barriers involved only permit limited drug delivery to the target 

ocular tissues. In this review, we described the development of welltolerated drug delivery systems that helps to overcome the factors 

limiting adequate drug delivery t o the glaucomatous patients targeting infected tissues with traditional techniques.  

Keywords: Drug delivery, Glaucomatous, Neuroprotection, Ocular surfaces, ophthalmic drugs 

t is known that glaucoma is the second most common 

cause of blindness in the world. Patients with glaucoma 

present with high ocular pressures that can cause optic 

neuropathy precipitating in the corresponding visual field loss 

[1]. Recent studies showed there were about 60 million people 

having optic neuropathy secondary to glaucoma globally [2]. 

These studies have shown that primary openangle glaucoma 

(POAG) leads to bilateral blindness in 9% of patients and 

unilateral blindness in 27% of patients, within 20 years of the 

first glaucomatous changes [3]. During 2010, an estimated 4.5 

and 3.9 million people were diagnosed with bilateral blindness 

due to open-angle glaucoma (OAG) and angle-closure 

glaucoma (ACG), respectively. The number increased to 5.9 

and 5.3 million in the year 2020 of bilaterally blind people due 

to OAG and ACG [2].  

Glaucoma is progressive and irreversible due to which 

visual field loss; however, attaining the normal range of the 

target intraocular pressure (IOP) within alleviates the 

progression of visual field loss. The initial management 

strategy for ‘high-risk’ glaucoma suspect or a patient 

diagnosed with OAG using topical anti-glaucoma drugs and 

lowering the IOP.  Glaucoma is a slowly progressive 

pathology that can result in the loss of peripheral vision, 

decreased contrast sensitivity, and loss of visual acuity. Due to 

the asymptomatic nature of the early phases of the disease 

most patients experience undiagnosed loss of vision until the 

advanced stages of the disease have occurred. Thus the disease 

is known as the “silent thief of sight”. This indolent optic 

neuropathy is characterized structurally by a loss of retinal 

ganglion cells and optic nerve axons. Glaucoma is the second 

leading cause of the world’s blindness with nearly 70 million 

cases worldwide and accounting for 12% of all cases of 

preventable blindness. It is estimated that by 2020, close to 4 

million Americans will have glaucoma with 50% undiagnosed 

and approximately 120,000 individuals developing blindness 

[4].In developing countries, where the access to adequate care 

and therapies is limited, people are going blind from a disease 

that can be successfully treated. Patients in these countries may 

not have the ability to get to their clinics routinely for refills 

and exams.  

However, even in the US with ready access to medical 

care and pharmaceuticals, glaucoma continues to progress in 

many patients. Often poor IOP control is due to poor 

compliance and adherence to daily topical treatment regimens 

or inadequate, complex dosing regimens. Despite effective 

monotherapy agents, data has shown that upwards of 40% of 

OAG patients require combination therapy for IOP reduction 

with close to 75% of glaucoma patients requiring adjunctive 

therapy after five years. The complexity, cost, and 

administration issues with multiple medications further reduce 

patient compliance and adherence. Prescribing pharmacy 

claims data show the vast majority of patients do not take their 

I 

mailto:tahilanipraveen@gmail.com


Rai et al                                                                                                                   Mindful-based Stress Reduction Impact  

Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 39  

topical medications or renew their prescriptions, resulting in 

patients regularly missing doses. Retrospective population-

based data suggests a minority of patients consistently adhere 

to their topical medication. A sustained mode of delivery 

where the patient’s dependence on daily self-instillation is 

eliminated could dramatically improve these statistics [8]. 

Various studies have highlighted the shortcomings of treatment 

regimens, drug efficacy factors causing short precorneal 

residence time, reduced absorption, and rapid turnover of 

lacrimal fluid, extensive nasolacrimal drainage, rapid blinking 

reflex, human factors compliance, and persistence [5-7].  

METHODS 

For this review article we searched different electronic 

databases such as PubMed, Google Scholar. Studies were 

included from 1975 to 2020 available in the English language 

only.   

Ocular Inserts- For the release of therapeutic drugs over a 

prolonged duration ocular inserts are sterile drugimpregnated 

microdevices placed in or around the eye. Based on their 

physical and chemical properties, the inserts are classified into 

insoluble, soluble, or bioerodible [9]. The contact time of the 

drug to a few days increased the ocular surface after insertion, 

thereby increasing manifold bioavailability due to reduce 

washout by tears.  

Pilocarpine Ocular Inserts- In 1976, Bensinger et al. 

demonstrated the use of a synthetic biosoluble matrix in the 

conjunctival cul-de-sac to increase the contact time of 

pilocarpine with the corneal tear film for intraocular pressure 

(IOP) control. Different doses ranging from 0.5 to 2 mg, 32 h 

post-insertion recorded with a significant reduction in the IOP 

[10]. The IOP had the maximum lowering of 6.25 ± 2.48 

mmHg on the placement of 0.5 mg pilocarpine inset. While, a 

higher dose of 1.5 mg pilocarpine reduced the IOP by 8.14 ± 

0.96, 5 h post-placement. A significant reduction in the IOP 

was noted at 32 hours after insertion of the 1 mg pilocarpine.  

Soluble Ophthalmic Drug Inserts- As the soluble ocular drug 

insert (SODI) is an oval-shaped ocular insert made up of a 

copolymer of polyacrylamide, ethyl acrylate, and 

vinylpyrrolidone. Maichuk [11] first reported and used to 

administer drugs including pilocarpine through the inferior cul-

de-sac. The drug insert converts into a viscous polymer 

solution after 10 to 15-sec contact with the tear film followed 

by conversion to a polymer solution within 60–90 min of 

administration.  

Ocusert- Ocusert was one of the earliest models of ocular 

inserts developed by Armaly and Rao [12], made 

commercially available by Alza Corporation Inc. Ocusert 

releases the drug at a constant rate of 20 or 40 μg/h for an 

extended period of 7 days. Pilocarpine was loaded in a 

polymer membrane system consisting of an inner layer of 

pilocarpine in alginate gel di-(Ethylhexyl) phthalate for a 

release enhancer sandwiched between two outer layers of 

ethylene-vinyl acetate (EVA) designed to release the drug at a 

predetermined constant rate. Zimmerman et al. studied 

Pilocarpine delivery in 40 patients for Ocusert with a target 

release rate of 20 µg/h. Initially, the mean IOP was recorded to 

be 25.6 ± 5.6 mmHg. IOP was reduced to 19.9 ± 3.9 mmHg by 

using pilocarpine-loaded Ocusert. The study reported that the 

patients do not prefer the pilocarpine drops over the Ocusert 

system. No side effects from the Ocusert were noted [13]. 

Pavan-Langston et al. studied 29 patients who showed that 

pilocarpine-loaded Ocuserts releasing either 20 or 40 μg/h of 

pilocarpine a satisfactory control of the IOP. The Ocuserts side 

effects were minimal or absent [14]. Ocusert did not become a 

widely accepted method of drug delivery, although the clinical 

studies showed positive outcomes. This is because of the 

difficulty of device insertion, failure in satisfactorily 

controlling IOP in many patients, ejection of the device from 

the eye, irritation during insertion, and the difficulty of device 

insertion [15].  

Poly (Vinyl Methyl Ether-Maleic Anhydride) Anhydride 

(PVMMA) Ocular Inserts- PVMMA and its alkyl monoesters 

are bioerodible polymers used for controlled timolol release in 

animals. The systemic effect of timolol is reduced by the 

polymer-assisted drug release. Finne et al. [16] found a lower 

steady-state concentration (1.0 ± 0.1 ng/ml) in plasma three 

hours after administration and a peak concentration of timolol 

in tear fluid (64 ± 9 μg/ml). They also reported a 1.6-fold 

increase in timolol concentration in tears (104 ± 8 μg/ml) on 

the addition of disodium phosphate as a buffer.  

Collagen shield- Collagen shields as postoperative corneal 

bandages developed by Dr. Svyatoslav Fyodorov [17]. 

Bloomfield et al. developed the drug delivery model for the 

collagen shields. A higher level of gentamicin in the tear film, 

tissues in rabbit eyes using wafer-shaped collagen inserts 

impregnated with gentamicin as compared with ointment, eye 

drops, and subconjunctival injection demostrated by 

Bloomfield et al. [18]. Collagen shields, were loaded with 

hydrophilic drugs in the collagen matrix by soaking a dry 

shield in the aqueous solution of the drug. The water-insoluble 

drugs are directly added to the shield during the manufacturing 

process. Agban et al. [19] developed cross-linked collagen 

shields consisting of nanoparticles of titanium dioxide (TiO2), 

zinc oxide (ZnO), polyvinyl pyrrolidone (PVP), and capped 

zinc oxide (ZnO/PVP) for controlled delivery of pilocarpine 

hydrochloride in glaucoma patients over a prolonged duration 

that undergoing animal trials. The results from the group show 

a sustained release of pilocarpine hydrochloride when cross-

linked with ZnO/PVP nanoparticles for 14 days.  

Ocufit SR- Developed by Escalon Ophthalmics Inc. is a 

flexible rod-shaped silicon elastomer device designed for 



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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 40  

retention in the conjunctival fornix for controlled release of 

drugs over long periods. The different models are a maximum 

of 1.9 mm in diameter and range between 25 and 30 mm in 

length. Katz and Blackman [20] later reported that expulsion 

of rod-shaped devices was significantly less frequent than that 

of oval, flat inserts. The insoluble Ocufit had favorable 

properties of both long retention and sustained drug release. In 

70% of the cases, the upper fornix placebo device was retained 

for two weeks or more.  

Minidisc- Bawa et al. [21] developed the Minidisc or Ocular 

Therapeutic System (OTS) the miniature contact lens with a 

diameter of 4–5 mm with a convex and a concave face latter 

conforming substantially to the sclera of the eye. The minidisc 

is a polymer of hydroxyethyl methacrylate and ethylene glycol 

methacrylate. The size and shape of the OTS allow easy 

placement of the device under either upper or lower lid without 

any foreign body sensation, distortion in vision, or decreased 

oxygen permeability.  

New Ophthalmic Delivery System (NODS) - NODS is used 

for delivering drugs in precise amounts to the eye through the 

lower conjunctival sac using a water-soluble film loaded with 

the drug [22]. The device consists of 20µm-thick, 4 × 6 mm2 

medicated flag, attached to a 0.7-mmlong paper-covered 

handle and a 3- to the 4-µm-thick membrane. NODS is 

manufactured using water-soluble polyvinyl alcohol (PVA). 

Greaves et al. [23] used radiolabeled NODS loaded with 

pilocarpine nitrate to evaluate the pharmacokinetics and 

bioavailability in human subjects.   

Topical bimatoprost ocular insert- A bimatoprost-loaded 

insert consisting of a silicone matrix with a polypropylene 

backbone for sustained delivery to treat glaucoma underwent 

randomized phase II clinical trial [24]. The diameter of the 

insert ranged from 24 to 29 mm and was placed between the 

upper and lower fornices. The bimatoprost ocular insert elutes 

the drug at a variable rate for six months, depending on the 

polymer-drug matrix properties. In 2016, De Souza and 

colleagues developed an ocular insert with mucoadhesive 

properties developed from polymers of chitosan. The data from 

the in vitro studies showed sustained release of brimonidine 

tartrate. Moreover, the authors highlighted the adherent 

properties of the chitosan-based polymer on the conjunctiva. 

They also confirmed the rate of constant release for a 

prolonged period of 30 days without an initial burst. The insert 

had biocompatibility with the surrounding ocular tissues [25].  

Patient education continues to be a significant challenge when 

it comes to the successful use of the inserts as it requires fine 

manual techniques to manipulate and place the insert. It was 

seen that the level of education and age continue to be the 

factors that govern the success of these devices when used for 

glaucoma [26]. Hitoshi et al. studied the efficacy of 

ophthalmic inserts of timolol based on poly (2-hydroxypropyl 

methacrylate) and poly (2-hydroxyethyl methacrylate) 

polymers. The results from the study indicated that the 

prepared inserts resulted in a controlled release and an 

improved ocular bioavailability of timolol [27].  

Soak and Release- Waltman and Kaufman [31] first 

demonstrated the potential use of hydrophilic polymers of 2-

hydroxyethyl methacrylate (HEMA) for drug delivery using 

fluorescein stain. In 1974, Hillman demonstrated the delivery 

of antiglaucoma drugs through soft contact lenses. He used 

polymers of vinylpyrrolidone soaked in 1% pilocarpine for 

drug delivery. He reported the system to be as efficacious as 

4% pilocarpine topical eye drops [32].  

Microemulsion Loaded Lenses- The microemulsions for drug 

dispersal were favored due to the thermodynamic stability, 

high drug-loading capacity, ease of preparation, increased 

wettability, and easy tailoring of the drug release pattern. 

Multiple groups have developed drug-loaded microemulsion-

incorporating contact lenses [48]. Gulsen and Chauhan 

encapsulated timolol in microemulsion stabilized within a 

silica shell using octadecyltrimethoxysilane (OTMS), followed 

by dispersion in a hydrogel lens. This model has shown 

sustained release of up to 8 days without affecting the 

transparency of the lens [33]. Li et al. [34] developed contact 

lenses loaded with timolol, with oil-in-water-type 

microemulsions using a combination of ethyl butyrate, and 

Pluronic F127. The group fabricated the microemulsion-laden 

gels, ethyl butyrate/water microemulsions stabilized by 

Pluronic F127 surfactant, and subsequently polymerized after 

the addition of HEMA.  

Vitamin E–loaded Lenses- Chauhan et al. developed the 

technique using Vitamin E as an in-situ transport barrier for 

timolol. The drug release was significantly increased by 

elevating the loading concentration of Vitamin E from 10% to 

40% in contact lenses [28]. The group demonstrated a 

quadratic increase in drug release duration in Vitamin E 

loading. Loadings of 10% and 40% Vitamin E increased the 

release time of timolol by a factor of about 5 and 400, 

respectively. However, Vitamin E loading in the lens led to an 

increase in lens sizes, a reduction in oxygen diffusion, and a 

significant decreament in ion permeability.  

Film Impregnation in Contact Lens- Ciolino et al. [35] 

designed a latanoprost-eluting contact lens for treating 

glaucoma, manufactured by encapsulating the drug film 

enclosed in methafilcon lenses. These lenses have shown 

sustained release for up to 1 month in glaucomatous monkeys. 

The amount of drug delivered to the eye exceeded or was 

comparable to the delivered topical drops. Contact lenses with 

polymer-drug films (40–45 mm in thickness) demonstrated an 

initial burst of latanoprost in the aqueous humor, a steady 

concentration was similar to the average hourly concentration 



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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 41  

delivered from a drop of commercially available latanoprost 

solution [52].  

Enzyme-triggered Timolol Release- Kim et al. [36] 

embedded nanodiamonds (NDs) loaded with timolol in contact 

lenses. The ND–nanogel embedded contact lens acts as an 

enzyme trigger for the delivery of timolol. The nanogels 

sequester timolol before activating the lysozyme that causes 

chitosan degradation and subsequently allows sustained drug 

release. After 24-h treatment with lysozyme, the total steady 

drug release from the lens was 9.41 μg.  

Intraocular Implants 

Intravitreal Implants- Intravitreal implants are devices 

capable of delivering drugs for a prolonged duration in the eye. 

Although surgical implants present a viable option for long-

term drug delivery, the invasive nature of the initial and 

subsequent surgical procedures to remove the implants does 

not make them a favorable choice for drug delivery. 

OZURDEX is a degradable dexamethasone intravitreal 

implant produced by Allergan, which was used to treat 

macular edema and noninfectious uveitis [53]. The device 

slowly degrades after implantation in the vitreous while 

delivering dexamethasone. The manufacturer conducts clinical 

trials of the implants loaded with brimonidine tartrate in the 

proprietary NOVADUR poly (lactic-coglycolic acid) (PLGA) 

intravitreal polymer matrix platform for the management of 

geographic atrophy due to agerelated macular degeneration. 

Topical daily ophthalmic brimonidine tartrate drops were 

prescribed for IOP reduction and neuroprotective effect. If the 

NOVADUR PLGA platform implants with brimonidine 

tartrate are approved, they can also be adapted for use in 

glaucoma patients [37].  

Subconjunctival Inserts-The subconjunctival inserts were 

used as implants as a replacement for viscoelastic depot 

delivery injections. The VS101 ocular insert was one such 

insert developed by ViSci Inc. in 2014 and later underwent a 

phase I/II multicentric randomized control study to evaluate 

the safety and effectiveness of subconjunctival latanoprost 

insert in subjects with ocular hypertension or OAG [38].  

PCL-PEG Inserts-Ng and colleagues used biodegradable 

microfilm synthesized by a combination of poly (lactide)/poly 

(ε-caprolactone) (PLC) and poly (εcaprolactone)/poly 

(ethylene glycol) (PLC/PCL-PEG). The polymer was loaded 

with timolol maleate and inserted by conjunctival dissection 

[39]. The authors reported a decrease of 50.1% ± 8.5% in IOP 

from baseline in primates with ocular hypertension, which was 

sustained for 140 days.  

AP-PCL Inserts-Alkoxylphenacyl-based polycarbonate 

polymers in combination with polycaprolactone (AP-PCL) 

were used by Manickavasagam et al. [40] for sustaining 

delivery of brimonidine tartrate for three months. The major 

drawback attributed to the subconjunctival inserts is the 

requirement of a surgically invasive procedure which creates a 

small opening in the conjunctiva with a possibility of 

subconjunctival migration, infection in need of an Operating 

Room procedure for insertion/removal of the device.  

Micro Electro-mechanical System-The system termed as 

micro electro mechanical system (MEMS) works on the 

principle of bubble generation by electrolysis to mechanically 

push the loaded drug out of the reservoir. The device, currently 

in a preclinical development phase, also allows loading the 

drug multiple times [41]. Saati et al. demonstrated the use of 

the MEMS pumping mechanism was based on electrolysis 

connected to a drug refill port a check valve to control 

delivery. The procedure is similar to the implantation of a 

glaucoma aqueous drainage device.  

Liposome- The liposome-encapsulated drug was delivered as a 

solution as an eye drop. Natarajan and colleagues used 

latanoprost-loaded egg-phosphatidylcholine liposomes for 

delivery. The liposomes remained stable for at least six months 

on storage at 4°C and at least one month at 25°C. A sustained 

release of 60% of latanoprost was achieved by two weeks in 

vitro. A high sustained IOP-lowering effect was recorded in 

liposome-treated animals (4.8 ± 1.5 mmHg) compared with 

daily administration of topical latanoprost (2.5 ± 0.9 mmHg) 

beyond 90 days [42]. Monem and colleagues used 

multilamellar vesicles (MLVs) as a vehicle for delivering 

pilocarpine. They reported neutral MLVs encapsulating 

pilocarpine HCl exhibited the most prolonged efficacy in the 

reduction of IOP. They also reported negatively charged 

MLVs encapsulating pilocarpine HCl exhibited a significantly 

shorter period of drug action [43]. The group speculated that 

the frequency of administration of drug administration in 

humans would be reduced to half with the usage of MLV 

vehicles, thus promoting better compliance.  

Polymeric Nanoparticles- Due to their molecular-scale size, 

nanoparticles efficaciously deliver drugs in the anterior 

chamber in the posterior compartment via the bloodaqueous 

and the blood-retina barrier, respectively [44]. Different types 

of nanoparticles were classified based on the origin of the 

constituent monomers and its emphasis was laid on effective 

drug loading on the nanoparticles through the process such as 

electrospraying and electrospinning. Mehta et al. demonstrated 

a single-needle electrohydrodynamic process for adding a 

stable nanocoating to the contact lenses with timolol maleate. 

The in vitro studies showed biphasic release of the drug, with 

an initial burst release followed by sustained release [45].  

Chitosan-based Polymeric Nanoparticles- Chitosan, a 

2amino-2-deoxy-beta-D-glucan, is being widely tested for 



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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 42  

synthesizing nanoparticles for drug delivery [46]. The 

biodegradable, biocompatible, and mucoadhesive properties of 

chitosan make it highly suitable for delivering antiglaucoma 

drugs. Li and colleagues [47] developed chitosan nanoparticles 

loaded with beta-adrenergic agent betaxolol, prescribed for 

lower IOP. The ex vivo data published by the authors show a 

1.75 times higher value compared with the topical eye drops. 

Zhao and colleagues [49] have developed timolol maleate–

loaded nanoparticles from glycosylated polymers of chitosan 

for ocular delivery. The authors reported an augmented 

transcorneal penetration due to high lipid solubility. The 

authors reported that the data from the in vivo experiments 

showed a sustained release over a significantly longer duration 

of time. Mehta et al. used electrohydrodynamic atomization of 

timolol maleate–loaded PVP and poly (N-isopropyl 

acrylamide). The authors used the formulation approach for 

sustained timolol maleate release used the combination of 

chitosan, borneol and reported the biphasic and triphasic 

release, depending on composition [49].  

Poly (Lactic-co-glycolic Acid) Nanoparticles- PLGA is a 

copolymer of cyclic dimers (1, 4-dioxane-2, 5-diones) of 

glycolic acid and lactic acid [50]. Salama and colleagues [51] 

used PLGA nanoparticles for the delivery of brinzolamide 

subconjunctivally and reported the release of the drug was 

prolonged for a period of up to 10 days after a single dosage. 

Khan and colleagues used PLGA-based nanoparticles for the 

delivery of forskolin, a natural extract with potent 

noradrenergic stimulatory action on adenylate cyclase [52, 53]. 

The authors reported a steady release of the drug from the 

PLGA polymer, with 90% release over 72 h compared with 

eye drops (96.6% release in 12 h).  

Gelatin Nanoparticles- The ease of availability and high 

biocompatibility make gelatin a favorable polymeric vehicle 

for the delivery of antiglaucoma drugs to the eye. Recently, 

Shokry and colleagues reported the use of gelatin nanoparticles 

for delivering timolol maleate and reported increased 

mucoadhesion and transcorneal permeability due to its positive 

charge attracted to negatively charged lipid layers in the cornea 

[54]. The in vitro release studies showed a burst effect of 

timolol release followed by a sustained profile over a 

prolonged duration. The in vivo studies in the albino rabbits 

showed a sustained and higher efficacy in IOP lowering. In 

another study, Liao et al. [55] used silica-based mesoporous 

nanoparticles for pilocarpine with gelatin coating. The in vitro 

data showed a 36-day release profile of the gelatin-coated 

mesoporous nanoparticles with an efficacious in vivo IOP-

lowering effect for 21 days.  

Propoxylated Glyceryl Triacylate Nanoparticles- Jung et al. 

[56] developed a contact lens based on the principle of 

dispersing timolol-loaded propoxylated glyceryl triacylate 

(PGT) nanoparticles within the lens. Timolol–PGT particles 

release the drug for an extended period (>30 days at room 

temperature) by hydrolysis of the ester bond. The 

bioavailability of timolol delivered through the contact lens 

showed 50% bioavailability as compared with only 1–2% 

through eye drops.  

PGT–ethylene Glycol Dimethacrylate Nanoparticles- Jung 

and Chauhan [57] also developed a lens with highly cross-

linked particles consisting of monomeric units with multi vinyl 

functionalities such as PGT and ethylene glycol dimethacrylate 

(EGDMA). The 3.5-nm nanoparticles encapsulated 48–66% of 

the drugs. The rate constant of ester hydrolysis was 

significantly less than those of the previous models developed 

by the same group, possibly due to steric effects and the low 

water content of the highly cross-linked hydrophobic particles. 

The nanoparticles dispersing timolol were encapsulated with 

linked nanoparticles enclosed within contact lenses, which 

increases the duration of drug release from 1 to 2 h to about 

four weeks. The drug-dispensing particles were dispersed in 

hydroxymethyl methacrylate (HEMA) gels that were 

commonly used for manufacturing contact lenses. Xu and 

colleagues [58] developed micelles that could be loaded on the 

contact lenses for sustained release of timolol and latanoprost 

simultaneously for management of glaucoma. The micelles 

were synthesized by free radical polymerization of the HEMA 

monomer with timolol and latanoprost. The lenses released 

timolol and latanoprost in tear fluid for 144 and 120 h, 

respectively. The in vivo data showed sustained timolol and 

latanoprost release for 120 and 96 h in tear fluid, respectively.  

Nanospheres /Microspheres- The penetration of drugs loaded 

on the nanosphere depends on the size, charge, architecture, 

and surface of the carrier nanoparticle systems [59, 60]. The 

architecture of the nanospheres consists of a di-block 

copolymer that is a hydrophobic block [polycaprolactone 

(PCL)], a hydrophilic component [polyethylene glycol (PEG)]. 

The unique structure of nanospheres allows a longer residence 

time on the surface of the cornea to provide the drug with a 

carrier followed by fusion with the corneal epithelial 

membrane, hence reducing the dosing frequency [61]. Chiang 

et al. [62] initially reported 6 mmHg with brimonidine 

polylactic acid (PLA) microspheres that results in reduced IOP 

for one month in normotensive rabbit eyes. The in vitro 

analysis of the brimonidine microspheres showed a sustained 

release of the drug for 35 days.  

OHR1031- It is a macromolecular drug for glaucoma 

management that incorporates into microparticles using a 

dissolvable hydrogel template technology [63]. The drug is 

dissolved into a PLGA polymer-solvent mixture, and the 

microparticles are formed using the dissolvable template 

technology. The median size of drug-loaded particles is 60 μm. 

The authors reported that the OHR1031 content in the 

microparticles was 57%-100% incorporation efficiency. The 



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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 43  

drug release rate was nearly zero-order for over three months 

with virtually no initial burst.  

SoliDrop- SoliDrop by Otero Therapeutics consists of a 

thermoresponsive hydrogel carrier and drug-loaded polymer 

microspheres. On administering a single brimonidine-loaded 

gel/microsphere drop, the IOPlowering efficacy (reduced by 

30% of baseline IOP) was comparable to that of rabbits 

receiving twice-daily, standard brimonidine drops for 28 days. 

The gel drops were retained in the fornix during the entire 

period of the study [64].  

ENV 515/Travoprost XR- ENV515 PGA/travoprost XR 

therapy is a particle replication in a nonwetting templatebased 

biodegradable polymer drug delivery system. The implant is 

rod-shaped and fits the anatomy of the iridocorneal angle in 

the anterior chamber, allowing its administration via an 

acceptably sized needle. The result from the phase II clinical 

trial reported that a single low dose of ENV515 decreases the 

mean IOP by 6.7 ± 3.7 mmHg over eleven months. The mean 

IOP after a single low dose of ENV515 was 19.5 mmHg over 

the 11 months [68].  

Bimatoprost SR- Bimatoprost SR is a biodegradable implant 

for the decrement of IOP with a 4-month sustained release 

period [69]. In the first phase III clinical study, Bimatoprost 

SR reduced IOP by 30% over the 12-week primary efficacy 

period. The results showed no requirement of supplementary 

treatment for IOP lowering for one year after the last implant 

insertion. The magnitude of IOPlowering efficacy with 

Bimatoprost SR observed in this study is similar to that 

observed with daily topical prostaglandin analogs. Bimatoprost 

SR was well tolerated in the majority of patients.  

Graybug- Graybug is a drug-encapsulated microparticle 

formulation to provide continuous IOP lowering that is 

administrated by the treating physician every 3 –6 months 

using a subconjunctival injection. GB-203 is a preclinical stage 

dual mode of action, single molecular entity agent that can 

hydrolyze into an active agent that has the potential to lower 

IOP and a second active agent that can provide longterm 

neuroprotection [70]. Another pilot polymer depot formulation 

of GB-6249-103 developed on the Graybug platform safely 

has been shown to deliver its payload in a sustained manner 

both in vitro and in vivo [71]. A significant reduction in IOP 

was observed within the first week following injection of the 

formulation in rabbits. The results recorded a sustained 

maximum IOP lowering of ~20% over two months.  

OTX-TP- The OTX-TP (Ocular Therapeutix) delivered 

travoprost to the ocular surface via an intracanalicular punctal 

plug for up to three months, resorbs, and drains through the 

nasolacrimal system [72]. It consists of PEGbased hydrogel 

with embedded travoprost–loaded PLA microspheres. These 

microspheres slowly degrade and show a sustained drug 

release over 30 days. Perera et al. [73] in a study reported a 

100% retention rate of the plugs, ten days post-implantation, 

and a reduction in IOP by 5.4–7.5 mmHg. It is minimally 

invasive, contains fluorescein to monitor any retention, and 

clears from the body through absorption. The studies have 

shown an enhanced therapeutic benefit for 90 days with a 

consistent 90% retention rate. The phase II trial did not find 

any serious adverse effects and showed only slightly less 

hypotensive effects as compared with timolol.  

Latanoprost Punctal Plug Delivery System- Goldberg and 

Williams [74] used the Latanoprost Punctal Plug Delivery 

System (L-PPDS) for lowering IOP in OAG patients. The data 

reported by the authors showed a reduction in mean IOP by 5.7 

mmHg. They also reported that 60% of subjects in the study 

showed at least 5 mmHg or higher IOP reduction, and 47% of 

the subjects showed a reduction of at least 6 mmHg. A 

statistically significant 22.3% mean change in IOP was 

recorded in the subjects with L-PPDS when compared with 

controls.  

Evolute- Evolute, a punctal plug delivery system developed by 

Mati Therapeutics has been tested with latanoprost in patients 

with OAG or ocular hypertension [75]. The plug consists of a 

drug core, which allows unidirectional sustained drug elution 

into the tear film. In phase II clinical trial, an overall punctal 

plug retention rate of 96% was reported at 12 weeks. In the 

second phase, the retention rate of plugs was 92% in the 12th 

week. The punctal plugs loaded with travoprost reduced the 

pressure by 7 mm compared with a 5-mmHg decreased 

pressure with latanoprost.  

Pentablock copolymer gels- The pentablock copolymer gels 

were used as a vehicle for topical and intraocular delivery of 

glaucoma drugs like bimatoprost. The Food and Drug 

Administration (FDA) has approved five different pentablock 

copolymers for use in the eye. These include polyglycolic acid 

(PGA), PCL, PEG, PLA, and PLGA [76]. The drug was 

introduced as an eye drop, then changes physical 

characteristics based on body temperature at contact. The 

change in viscosity gives the vehicle copolymer gel-like 

characteristics gets accumulated under the lower palpebra, 

releasing the drug over a longer period.  

Microneedles- Microneedles are drug delivery devices 

manufactured using metals or polymers with dimensions 

between 10 and 200 μm. The ultra-dimensions of these devices 

make the drug delivery less invasive and more targeted to the 

sites of drug action. Jiang et al. used 500 to 750 μm long-

coated stainless-steel microneedles delivering pilocarpine into 

the anterior chamber via the intrascleral route. The authors 

reported a 45-fold increase in drug absorption compared with 

conventional eye drops [77, 78].  



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Vol 1 | Issue 2 | Jul – Sep 2022                                                                                       Indian J Pharm Drug Studies | 44  

DISCUSSION  

In this review article, we described the development of 

welltolerated drug delivery systems that helps to overcome the 

factors limiting adequate drug delivery to the glaucomatous 

patients targeting infected tissues with traditional techniques. 

Ocusert did not become a widely accepted method of drug 

delivery although the clinical studies showed positive 

outcomes the difficulty of device insertion, failure in 

satisfactorily controlling IOP in many patients, ejection of the 

device from the eye, irritation during insertion, and the 

difficulty in device insertion [14]. The ease of availability and 

application of Therapeutic contact lenses make them an ideal 

drug delivery system. The therapeutic contact lenses help in 

sustained and regulated ocular drug delivery due to their 

unique properties like extended wear and more than 50% 

bioavailability comparison with eye drop formulations [27, 

28]. Soft contact lenses are water-soluble polymeric hydrogels 

crosslinked to form networks. These hydrogel lenses are 

widely used for drug delivery, even though the delivery of 

watersoluble drugs, such as timolol and dorzolamide, elutes 

from the highly hydrated polymer networks rapidly [29].  

In comparison, the soft contact lenses manufactured by 

polymerization N, N-diethyl acrylamide methacrylic acid 

deliver timolol over a prolonged period [30]. Injectable 

systems are passive delivery systems capable of delivering 

medications to the target tissues for an extended period. The 

injectable systems are typically implanted at the site of drug 

release through a minimally invasive procedure, usually in an 

outpatient setting. The injectable systems use a polymer 

delivery vehicle to prolong delivery up to a few months around 

the surrounding tissue. Both degradable and non-degradable 

polymers have been developed used as injectable systems for 

drug delivery in the eye [65]. Degradable PLGAs are materials 

of choice for developing such a system. The non-degradable 

alternative such as the polymer of ethylene-co-vinyl acetate 

may lead to an immune response due to the prolonged 

presence of a foreign body [66]. The rate of dispersion of 

drugs from these systems is variable, with an initially more 

massive quantity release. The water solubility of the drug 

affects the efficacy because hydrophilic drugs interact poorly 

with degradable polymers as they are hydrophobic [67].  

Several methods of treatment of glaucoma in the patient’s 

eye were discussed in this review and also, we discussed the 

development of the well-tolerated drug delivery systems that 

helps to overcome the limiting factor of adequate drug delivery 

systems. In the past, many studies have emphasized the 

importance of adherence, compliance, and persistence for the 

management of glaucoma. We know the available drugs are 

efficacious in lowering IOP and neuroprotection, the 

traditional methods of topical drug delivery have been not 

satisfactory due to poor target bioavailability, increased 

systemic absorption, and poor patient compliance.  

CONCLUSION 

This review described the direction and ongoing 

innovation/research to address the challenges of safer and 

more effective drug delivery challenges associated with the 

previous one. The majority of the devices studied in this article 

are currently in various stages of development and are not 

commercially available. The impact of these devices on the 

patients can only be gauged once they are available for clinical 

use and extensive clinical data are available for scrutiny. 

Notwithstanding the lack of data, the critical role of these 

devices in glaucoma management shortly needs to be 

emphasized.  

The potential of increasing patient compliance and 

persistence for optimum outcomes with the help of these 

devices is unprecedented. Eye drop installation has always 

been a challenge, especially in the geriatric and pediatric age 

group patients. Effective localized delivery will prevent drug 

loss due to systemic absorption and firstpass metabolism 

thereby, minimizing drug wastage. The prevalence of ocular 

surface disease in patients installing antiglaucoma drugs with 

added preservatives may be overcome with the newer devices. 

The most significant advantage of these devices was the 

improved quality of life of the patients who adhere to a strict 

regime of repeatedly putting eye drops throughout the day.  

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How to cite this article:  Rai A, Castro A, Brar J, Smith 

CR. Impact of Mindfulness-Based Stress Reduction 

Techniques on General Well-Being of Employees 

Working on a Behavioral Health Unit. Indian J Pharm 

Drug Studies. 2022; 1(2): 38-46.  

 

Funding: None                  Conflict of Interest: None Stated 

 

 

 

https://clinicaltrials.gov/ct2/show/NCT02371746.

