Drug-Eluting Contact Lens Technologies: History
View Latest Version
Please note this is an old version of this entry, which may differ significantly from the current revision.
Contributor:
Tina Lovrec-Krstič
,
Kristjan Orthaber
,
Uroš Maver
,
Tomislav Sarenac

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.
Method Mechanism Advantages Limitations References
Layered contact lenses Approaches:
  • The system can make use of different materials, for one of which the drug exhibits tropism, being less diffusible from that region.
  • Alternating layers, which degrade over time.
  • The layers retard diffusion, ensuring a more stable release.
  • Compromised gas permeability.
 [16][18][19]
Surface-modified contact lenses
  • Loading the drugs into already created polymers or attaching them to the lens surface.
  • Enables the attachment of drugs to either side of the lens selectively.
  • Can diminish kinetic friction coefficient.
 [20][21]
Soaking method
  • Contact lenses are soaked in the desired drug solution. Some of the drug adheres to the polymer matrix while the rest is dissolved in the aqueous phase before release.
  • The simplest, cost-effective, and conventional approach.
  • Higher drug bioavailability than eye drops.
  • Some of the drug adheres to the polymer matrix while the rest is dissolved in the aqueous phase before release.
  • The lens’ ability for drug uptake is highly dependent on the lens’ water content and thickness, the drug’s molecular weight, its concentration in the soaking solution and its solubility in the hydrogel matrix.
  • Lenses show a low affinity for several ophthalmic drugs.
  • Sterilisation and packaging processes might cause a premature release.
 [19][22][23][24][25][26][27][28]
Molecular imprinting
  • The targeted drug is mixed with functional monomers. After polymerisation, the drug is removed, and specific cavities in a 3D-polymer network are formed.
  • Molecular sites with high affinity increase the drug loading capacity while decreasing diffusion rates.
  • Drug affinity and its release profiles can be tailored.
  • Can be used with a variety of monomers (HEMA, MAA, MMA).
  • The optical and physical properties of the lenses can be altered by the structure of such hydrogels.
  • The gas and ion permeability is dependent on the material’s water content, which decreases with wear time, presenting an obstacle in extended wear uses.
 [19][29][30][31][32]
Colloidal nanoparticles
  • The formulated nanoparticular system is dispersed in different monomers (e.g., HEMA) and further polymerised (e.g., with EGDMA) and/or with photo inhibitors.
  • Can entrap drug molecules and attain better control over their release rate from contact lenses.
  • Prevent the interaction of drugs with the polymerisation mixture and provide additional resistance to the drug’s release.
  • Alter the lens’s physical and mechanical properties, such as gas and ion permeability, transparency and swelling behaviour.
 [19][33][34][35][36][37]
Supercritical fluid technology
  • Supercritical solvents, such as CO2, are used to drugs onto contact lenses. During the impregnation, the dissolution of drugs occurs in a supercritical solvent at conditions that are subcritical or supercritical, followed by an interaction with hydrogels.
  • Can be used to adjust the drug’s release kinetics without affecting the optical properties of the lens.
  • Limited loading of drugs with higher solid molar volume (such as dexamethasone) due to constraints in diffusion and uptake by contact lenses.
 [19][38][39]
Vitamin E as a release-modifying additive
  • Incorporation of vitamin E into lenses to act as a diffusion barrier.
  • Slows the drug release rate without significantly altering the lens’s bulk properties.
  • Very stable when incorporated into a lens due to its hydrophobic nature, having negligible solubility in the tear fluid.
  • Can prevent the oxidisation of drugs, such as cysteamine.
  • Reduces ion permeability and oxygen permeability.
  • Increases storage module due to changes in mechanical properties and protein absorption due to its hydrophobic nature.
 [16][19][40][41]

This entry is adapted from the peer-reviewed paper 10.3390/ma16103653

References

  1. Mitra, A.K. Role of Transporters in Ocular Drug Delivery System. Pharm. Res. 2009, 26, 1192–1196.
  2. Gote, V.; Sikder, S.; Sicotte, J.; Pal, D. Ocular Drug Delivery: Present Innovations and Future Challenges. J. Pharmacol. Exp. Ther. 2019, 370, 602–624.
  3. Lim, L.; Lim, E.W.L. Therapeutic Contact Lenses in the Treatment of Corneal and Ocular Surface Diseases—A Review. Asia-Pac. J. Ophthalmol. 2020, 9, 524–532.
  4. Musgrave, C.S.A.; Fang, F. Contact Lens Materials: A Materials Science Perspective. Materials 2019, 12, 261.
  5. Liechty, W.B.; Kryscio, D.R.; Slaughter, B.V.; Peppas, N.A. Polymers for Drug Delivery Systems. Annu. Rev. Chem. Biomol. Eng. 2010, 1, 149–173.
  6. Aghabegi Moghanjoughi, A.; Khoshnevis, D.; Zarrabi, A. A Concise Review on Smart Polymers for Controlled Drug Release. Drug Deliv. Transl. Res. 2016, 6, 333–340.
  7. Xu, J.; Xue, Y.; Hu, G.; Lin, T.; Gou, J.; Yin, T.; He, H.; Zhang, Y.; Tang, X. A Comprehensive Review on Contact Lens for Ophthalmic Drug Delivery. J Control. Release 2018, 281, 97–118.
  8. Stapleton, F.; Stretton, S.; Papas, E.; Skotnitsky, C.; Sweeney, D.F. Silicone Hydrogel Contact Lenses and the Ocular Surface. Ocul. Surf. 2006, 4, 24–43.
  9. Guzman-Aranguez, A.; Colligris, B.; Pintor, J. Contact Lenses: Promising Devices for Ocular Drug Delivery. J. Ocul. Pharmacol. Ther. 2013, 29, 189–199.
  10. Auffarth, G.U.; Apple, D.J. Zur Entwicklungsgeschichte Der Intraokularlinsen. Der Ophthalmol. 2001, 98, 1017–1031.
  11. Nicolson, P.C.; Vogt, J. Soft Contact Lens Polymers: An Evolution. Biomaterials 2001, 22, 3273–3283.
  12. Center for Devices and Radiological Health. Class II Daily Wear Contact Lenses—Premarket Notification Guidance Document; FDA: Silver Spring, MD, USA, 2020.
  13. Gonzalez-Chomon, C.; Concheiro, A.; Alvarez-Lorenzo, C. Soft Contact Lenses for Controlled Ocular Delivery: 50 Years in the Making. Ther. Deliv. 2013, 4, 1141–1161.
  14. Donshik, P.C. Extended Wear Contact Lenses. Ophthalmol. Clin. N. Am. 2003, 16, 305–309.
  15. The Editors of Encyclopaedia Britannica. PolyHEMA. Available online: https://www.britannica.com/science/polyHEMA (accessed on 10 May 2023).
  16. Dixon, P.; Shafor, C.; Gause, S.; Hsu, K.H.; Powell, K.C.; Chauhan, A. Therapeutic Contact Lenses: A Patent Review. Expert Opin. Ther. Pat. 2015, 25, 1117–1129.
  17. Makadia, H.K.; Siegel, S.J. Poly Lactic-Co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. Polymer 2011, 3, 1377–1397.
  18. Danion, A.; Arsenault, I.; Vermette, P. Antibacterial Activity of Contact Lenses Bearing Surface-Immobilized Layers of Intact Liposomes Loaded with Levofloxacin. J. Pharm. Sci. 2007, 96, 2350–2363.
  19. Maulvi, F.A.; Soni, T.G.; Shah, D.O. A Review on Therapeutic Contact Lenses for Ocular Drug Delivery. Drug Deliv. 2016, 23, 3017–3026.
  20. Danion, A.; Brochu, H.; Martin, Y.; Vermette, P. Fabrication and Characterization of Contact Lenses Bearing Surface-Immobilized Layers of Intact Liposomes. J. Biomed. Mater. Res. A 2007, 82, 41–51.
  21. Korogiannaki, M.; Samsom, M.; Schmidt, T.A.; Sheardown, H. Surface-Functionalized Model Contact Lenses with a Bioinspired Proteoglycan 4 (PRG4)-Grafted Layer. ACS Appl. Mater. Interfaces 2018, 10, 30125–30136.
  22. Li, C.C.; Chauhan, A. Ocular Transport Model for Ophthalmic Delivery of Timolol through P-HEMA Contact Lenses. J. Drug Deliv. Sci. Technol. 2007, 17, 69–79.
  23. Kim, J.; Chauhan, A. Dexamethasone Transport and Ocular Delivery from Poly(Hydroxyethyl Methacrylate) Gels. Int. J. Pharm. 2008, 353, 205–222.
  24. Maulvi, F.A.; Soni, T.G.; Shah, D.O. Extended Release of Hyaluronic Acid from Hydrogel Contact Lenses for Dry Eye Syndrome. J. Biomater. Sci. Polym. Ed. 2015, 26, 1035–1050.
  25. Ruben, M.; Watkins, R. Pilocarpine Dispensation for the Soft Hydrophilic Contact Lens. Br. J. Ophthalmol. 1975, 59, 455–458.
  26. Schultz, C.L.; Poling, T.R.; Mint, J.O. A Medical Device/Drug Delivery System for Treatment of Glaucoma. Clin. Exp. Optom. 2009, 92, 343–348.
  27. Xinming, L.; Yingde, C.; Lloyd, A.W.; Mikhalovsky, S.V.; Sandeman, S.R.; Howel, C.A.; Liewen, L. Polymeric Hydrogels for Novel Contact Lens-Based Ophthalmic Drug Delivery Systems: A Review. Contact Lens. Anterior Eye 2008, 31, 57–64.
  28. Maulvi, D.F. Effect of Timolol Maleate Concentration on Uptake and Release from Hydrogel Contact Lenses Using Soaking Method. J. Pharm. Appl. Sci. 2014, 1, 17–23.
  29. Zidarič, T.; Finšgar, M.; Maver, U.; Maver, T. Artificial Biomimetic Electrochemical Assemblies. Biosensors 2022, 12, 44.
  30. Alvarez-Lorenzo, C.; Hiratani, H.; Gomez-Amoza, J.L.; Martinez-Pacheco, R.; Souto, C.; Concheiro, A. Soft Contact Lenses Capable of Sustained Delivery of Timolol. J. Pharm. Sci. 2002, 91, 2182–2192.
  31. Schrader, S.; Wedel, T.; Moll, R.; Geerling, G. Combination of Serum Eye Drops with Hydrogel Bandage Contact Lenses in the Treatment of Persistent Epithelial Defects. Graefes. Arch. Clin. Exp. Ophthalmol. 2006, 244, 1345–1349.
  32. Byrne, M.E.; Salian, V. Molecular Imprinting within Hydrogels II: Progress and Analysis of the Field. Int. J. Pharm. 2008, 364, 188–212.
  33. Gupta, C.; Chauhan, A. Drug Transport in HEMA Conjunctival Inserts Containing Precipitated Drug Particles. J. Colloid Interface Sci. 2010, 347, 31–42.
  34. Jung, H.J.; Abou-Jaoude, M.; Carbia, B.E.; Plummer, C.; Chauhan, A. Glaucoma Therapy by Extended Release of Timolol from Nanoparticle Loaded Silicone-Hydrogel Contact Lenses. J. Control. Release 2013, 165, 82–89.
  35. Hsu, K.H.; Gause, S.; Chauhan, A. Review of Ophthalmic Drug Delivery by Contact Lenses. J. Drug Deliv. Sci. Technol. 2014, 24, 123–135.
  36. Gulsen, D.; Li, C.C.; Chauhan, A. Dispersion of DMPC Liposomes in Contact Lenses for Ophthalmic Drug Delivery. Curr. Eye Res. 2005, 30, 1071–1080.
  37. Gulsen, D.; Chauhan, A. Dispersion of Microemulsion Drops in HEMA Hydrogel: A Potential Ophthalmic Drug Delivery Vehicle. Int. J. Pharm. 2005, 292, 95–117.
  38. Costa, V.P.; Braga, M.E.M.; Duarte, C.M.M.; Alvarez-Lorenzo, C.; Concheiro, A.; Gil, M.H.; de Sousa, H.C. Anti-Glaucoma Drug-Loaded Contact Lenses Prepared Using Supercritical Solvent Impregnation. J. Supercrit. Fluids 2010, 53, 165–173.
  39. Yanez, F.; Martikainen, L.; Braga, M.E.; Alvarez-Lorenzo, C.; Concheiro, A.; Duarte, C.M.; Gil, M.H.; de Sousa, H.C. Supercritical Fluid-Assisted Preparation of Imprinted Contact Lenses for Drug Delivery. Acta Biomater. 2011, 7, 1019–1030.
  40. Peng, C.C.; Kim, J.; Chauhan, A. Extended Delivery of Hydrophilic Drugs from Silicone-Hydrogel Contact Lenses Containing Vitamin E Diffusion Barriers. Biomaterials 2010, 31, 4032–4047.
  41. Hsu, K.H.; Fentzke, R.C.; Chauhan, A. Feasibility of Corneal Drug Delivery of Cysteamine Using Vitamin E Modified Silicone Hydrogel Contact Lenses. Eur. J. Pharm. Biopharm. 2013, 85, 531–540.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
This entry is offline, you can click here to edit this entry!
Video Production Service
Feedback