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Lovrec-Krstič, T.; Orthaber, K.; Maver, U.; Sarenac, T. Drug-Eluting Contact Lens Technologies. Encyclopedia. Available online: (accessed on 10 December 2023).
Lovrec-Krstič T, Orthaber K, Maver U, Sarenac T. Drug-Eluting Contact Lens Technologies. Encyclopedia. Available at: Accessed December 10, 2023.
Lovrec-Krstič, Tina, Kristjan Orthaber, Uroš Maver, Tomislav Sarenac. "Drug-Eluting Contact Lens Technologies" Encyclopedia, (accessed December 10, 2023).
Lovrec-Krstič, T., Orthaber, K., Maver, U., & Sarenac, T.(2023, June 12). Drug-Eluting Contact Lens Technologies. In Encyclopedia.
Lovrec-Krstič, Tina, et al. "Drug-Eluting Contact Lens Technologies." Encyclopedia. Web. 12 June, 2023.
Drug-Eluting Contact Lens Technologies

Due to an ageing population and climate change, the number of ophthalmic patients will increase, overwhelming healthcare systems and likely leading to under-treatment of chronic eye diseases. Since drops are the mainstay of therapy, clinicians have long emphasised the unmet need for ocular drug delivery. Alternative methods, i.e., with better compliance, stability and longevity of drug delivery, would be preferred. Drug-loaded contact lenses are among the most promising and are a real step toward dropless ocular therapy, potentially leading to a transformation in clinical ophthalmic practice.

contact lens materials advanced ocular drug delivery dropless ocular therapy

1. Introduction

Numerous eye conditions, such as chemical or thermal burns, infectious corneal inflammations, optic neuropathies and macular disorders, finally result in very poor visual acuity, thus significantly reducing patients’ quality of life. It is presumed that due to climate change, the incidence of ocular disease might significantly increase, especially in diseases where UV-rays play a role, such as cataracts, age-related macular degeneration and eyelid cancer. Due to population displacement in regard to global warming and rising sea levels, large areas of the globe might end up with worse healthcare, more compromised access to regular examinations and a higher incidence of untreated chronic ocular illness. Poverty-related blindness might increase, on the one hand, while the ageing population in developed countries might further increase the pool of ocular patients. While topical therapy is still the first treatment choice, this method has some major drawbacks. Its efficacy often varies significantly due to subjective factors. Many patients find such an application difficult or even impossible, leading to reduced compliance, which results in poor management of specific eye conditions. Topical delivery media can be irritative and cause dry eye syndrome. Nonetheless, a significant proportion of the drug is drained by the lacrimal system, which connects to the nasal cavity. In recent years there has been an increasing number of examples where various other methods were studied, approaching ocular therapy with a “dropless” idea, addressing the unmet need for a more effective ocular drug-delivery system.
Anatomically and physiologically, the eye is also challenging in pharmaceutical terms. Static barriers (cornea, conjunctiva, blood-aqueous humour and blood-retina barriers), dynamic barriers (choroidal and conjunctival blood flow, lymphatic cleansing and dilution due to tear flow) and ocular transporter systems (ATP-binding protein family—P glycoprotein (P-gp) and multidrug resistance proteins (MRP) as well as amino acid and peptide transporters) pose a significant limiting factor in the local drug delivery [1]
Contact lenses are already successfully used for vision correction, while their potential as drug delivery devices is far from fully exploited. Researchers could consider contact lenses as an advanced delivery system for the eye, with a more controlled manner of drug release than common eyedrops, less likely to be affected by poor compliance [2]. While they have been successfully used in past research, researchers still feel that much can be improved in such devices. Presently, common contact lenses are also used to manage corneal injuries as mechanical protection and to promote healing [3]. They are made of various synthetic polymers, such as silicon and acrylate [4].
The current trends in the production of advanced delivery systems are leaning toward natural, biocompatible, smart and potentially cheaper polymers, mostly polysaccharides [5][6]. However, existing contact lenses have an undisputable, albeit clinically underutilised, potential to bind selected substances for advanced forms of topical therapy. Among the most promising methods of drug-binding are colloidal delivery systems (e.g., layered nanoparticles, nano- and micro-myceliums, polymersomes and layer-by-layer (LbL) structures) with the potential to overcome pharmaceutical barriers [2][7].
The development of non-invasive delivery systems, such as drug-eluting contact lenses with a prolonged release (of the substance), could result in substantial shifts in the ophthalmological practice, leading to a dropless therapy approach that could simplify therapy for patients and potentially require less follow up by eye professionals.

2. Lenses

2.1. Initial Considerations

Hydrogels, from which most lenses are made, are formed by linking monomeric chains into a matrix-like polymer. Each polymer exhibits unique properties, defined by the chemical group interactions and cross-linking degree [8]. Physical properties are one of the utmost considerations during contact lens design and quality control. Several of these are important when considering a material for use as a drug-laden contact lens system. Among these are their transparency, oxygen permeability, glass transition temperature, wettability and water content. Each of these has to meet certain requirements while simultaneously posing no limitations to the lens use. Transparency, as the lens’s optical clarity measure, must be above 92%. Some approaches can achieve such standards (surfactant-laden SCLs, minimum 98.5% transmittance), while others are somewhat lacking in this respect (liposome-laden Poly(2-hydroxyethyl methacrylate) (pHEMA) gels, 80% transmittance) [9]. Oxygen permeability presents another crucial characteristic of lenses. Its low values can result in unwanted effects, such as corneal oedema. Hence, adequate oxygen transfer is necessary for such systems, with the bare minimum being around 125 Dk/t. It depends on the system’s water content and is therefore limited by its water solubility [8]. Silicone hydrogels are sufficiently capable in this respect, with no substantial alterations in oxygen permeability even soaked in vitamin E to improve drug release times [9]. Wettability is the material property which helps determine the lens’ physiological compatibility and stability in lacrimal fluid and is determined by contact angle measurement. It can be affected by the addition of copolymers [9]. Water content affects comfort and oxygen permeability, which increase with the increase of the property above. It was shown that comonomers do not affect the water content in pHEMA, as is true with molecular imprinting for norfloxacin and fumarate release [9]. Finally, among the lens properties also, glass transition temperature plays an important role. It presents a reversible occurrence in which amorphous material changes from a hard and brittle state into a viscous and rubbery one with increased temperature. Amongst other things, this property also affects comfort. Monomer incorporations do not significantly alter it in pHEMA (compared to pure pHEMA), nor is it affected after the supercritical impregnation process or in the pendant cyclodextrin lenses [9].

2.2. Lens Materials

2.2.1. “Classical” Hydrogels

Since poly(methyl methacrylate) was developed in 1928 and commercialised in 1933, polymers have been used in various ways. This material, first discovered during World War 2, is biocompatible with a lack of rejection events after the pilots had suffered Plexiglass® splinter-induced eye trauma [10]. Since 1936, the material has been used in hard contact lenses. However, contact lenses were only popularised in 1954, with the advent of soft pHEMA corrective contact lenses. These polymers have glass-like clarity, which, coupled with lower density and better mechanical properties, made them the beginning of new copolymer lens designs [11].
Lens materials are either hydrophilic (which is indicated by the suffix “-filcon”) or hydrophobic (indicated by the suffix “-focon”). These labels are used according to their composition and physical properties. Such classification is mainly used to describe lens behaviour in care product solutions and in interaction with lacrimal fluid proteins [12].
Some of these materials are sufficiently hydrophilic to be used for extended wear. This is largely due to its wettability, enabling sufficient water absorption and retention, which facilitates oxygen absorption and subsequent transport to the cornea [13]

2.2.2. Silicone Hydrogels

Silicone hydrogels can be worked into a system which prevents hypoxia during closed-eye periods. They make for hard lenses, which are gas permeable, with sufficient optical clarity [11].
In general, these materials are strongly hydrophobic. For the contact lenses to work in lieu of this problem, it was necessary to prepare hydrogels that build on a combination of silicone components’ permeability coupled with the biocompatibility of hydrophilic contact lens materials. The result of such a combination is certain contact lenses approved for continuous wear for up to 30 days [14].
Since the release profiles of the drug-eluting contact lenses must be fitted to daily, weekly, or monthly disposable products, the time of permeance of the eye surface must remain a critical consideration [13].
Silicone hydrogels have a structure similar to classical hydrogels, with a significantly different chemical composition. Because of silicone’s hydrophobicity, the surface must be modified to improve its incompatibility with the ocular surface, resulting in discomfort. This is due to its poor surface wettability, which destabilises tear film and helps accumulate deposits. The latter can be solved by incorporating soluble polymers within the material, acting as internal wetting agents. These polymers must be oriented to form an interface between the lens, lacrimal fluid, or tear film. This makes them a great combination of a soft contact lens with excellent oxygen solubility in silicone.
Silicone hydrogel materials are made from a variety of monomers, with the main common property being the presence of silicone. Due to the monomer variety, these hydrogel materials exhibit a differing oxygen permeability, ranging from 60–175 barrers, which is considerably greater than its conventional counterparts. The resulting lenses also vary in stiffness, water content and surface characteristics. The two present hydrogels, FDA-approved for wear up to 30 nights with monthly replacement, are Lotrafilcon A and Balafilcon A. Both are also approved for therapeutic bandage lens uses. Lotrafilcon B is recommended only for daily wear, with up to six nights’ extended wear, while gayfilcon A and senofilcon are only recommended for daily wear [8].

2.2.3. pHEMA

PolyHEMA, with the IUPAC name of poly(2-hydroxyethyl methacrylate), is a soft plastic material used in soft lens production due to its water absorption and flexibility. It is created by polymerising monomer 2-hydroxyethyl methacrylate (HEMA), a clear liquid, a product of a reaction between methacrylic acid and ethylene or propylene oxide.
The contact lens is shaped by casting the HEMA monomer into a small, concave, spinning mould. This is then either heated or subjected to light or free radical initiators, causing the monomer to polymerise, creating long, multiple-unit chains.
pHEMA chains are usually 3D cross-linked into a complex network by a copolymerising compound. The resulting material is hard but absorbent, meaning it can absorb up to 60% of its weight in water. This results in a soft hydrogel, optically similar to the conventional hydrogels. It is also less irritating to the cornea [15].

2.2.4. PLGA

This type of polyester is PLA (poly lactic acid) and PGA (poly glycolic acid) polymer, and it is the best current biomaterial for drug delivery based on its design and performance [16]. Despite its advantageous properties, it is often combined with other polymers. Applying a certain material as a drug delivery device demands an in-depth understanding of the substance’s physical, chemical, and biological properties. With PLGA being a two-part polymer, one must account for both parts’ properties. While the PLA polymer can take either a highly crystalline (PLLA) or a completely amorphous (PDLA) form, with practically no physicochemical property differences, the PGA polymer only takes a highly crystalline form since it lacks methyl side groups [16].
Concerning solubility, PLGA is soluble in various common solvents, not limited to tetrahydrofuran, acetone, and ethyl acetate. It also biodegrades in contact with water since ester linkage tends to hydrolyse. The degradation can be retarded with PLA methyl side groups, which make the material more hydrophobic, with lesser water uptake, resulting in a slower degradation rate. The same degradation process is also responsible for some material parameter alterations, including the change in the glass transition temperature, water content, and molecular weight. All of these changes influence the release and degradation rates of incorporated drugs. Degradation, of course, isn’t the only factor which can influence the material’s properties. Others also include initial molecular weight, device size, water exposure, and storage [17].
The mechanical strength of the polymer, and thereby the device, also depends on various factors, including molecular weight and polydispersity index. The strength is one factor that determines the material’s suitability as a drug delivery device, while it can also influence the degradation rate through the aforementioned hydrolysis. With such contact lenses being drug delivery devices, it is also important to understand that the release rate is not only a function of the lens material but also of the drug used in the formulation [16]. All of the aforementioned properties, namely mechanical strength, swelling behaviour and hydrolysis, depend on the PLGA degree of crystallinity, which also depends on the used copolymer ratio. The decreased crystallinity, namely the fraction of matter in crystalline form, increases the hydration rate and the subsequent hydrolysis. There is a general rule: the higher the PGA content, the faster the degradation process, though the fastest degradation comes with a 50-50 polymer ratio [16]. Crystallinity and the melting point are dependent on molecular weight. Due to its glass transition temperature above 37 °C, the polymers in the body are glassy, with a fairly rigid chain structure [16].
PLGA composite formulations
Different drugs require various administration methods for optimal delivery, hence the need for different PLGA combinations with polyethylene glycol (PEG). Production of these copolymers is possible in di- or triblock molecules with different component orders. PEG chains in the diblock types orient themselves towards the aqueous phase, encapsulating their content, and creating a barrier, therefore reducing interactions with foreign molecules. This enhances shelf stability, though it reduces drug and protein encapsulation efficiency [16].
Covalently coupled blocks with an esther link can render triblock copolymers into thermogels: free-flowing solutions at low temperatures and high viscosity gels at body temperature. These copolymers combine the hydrophilicity of PEG segments with the hydrophobicity of PLGA segments to achieve such thermos-responsive characteristics. Drug release from such formulations may be achieved either via diffusion from the hydrogel during the initial phase or through later erosion of the hydrogel matrix [16].

3. Methods of Binding Drugs into/to Lenses

The important aspects of drug delivery systems are an appropriate delivery duration, biodistribution, and concentration for the desired therapeutic effect. This means that the design must consider the degradation and clearance of the delivery system and the drug itself. The biodistribution and pharmacokinetics of the polymer in question are dose-dependent and non-linear and also depend on the PLGA system composition [16]. Table 1 summarises all the drug-binding methods to contact lenses described, with their advantages and limitations.
Table 1. Methods of binding drugs into/to lenses. The basics of drug-binding mechanism and methods’ advantages and limitations are described, with relevant references listed.


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Subjects: Ophthalmology
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