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User:RFWILLI/Drug-Eluting Contact Lens

Drug-Eluting Contact Lens


Overview

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Drug eluting contact lenses are designed to promote provide extended, controlled release of a drug. Drug eluting contact lenses may circumvent issues of limited absorption, poor compliance and systemic side effects posed by eye-drops – the current leading ocular drug delivery vehicle. Contact lens drug delivery holds the potential to drastically increase the amount of drug absorbed by the eye and delivered to the tear film by achieving and maintaining high drug levels on the surface of the eye [1]. Additionally the therapeutic lenses would decrease the necessary frequency of doses required by eye drops and would thereby improve compliance [2].

History

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Interestingly it was as early as the 1960’s that the idea of using contact lenses for drug delivery was first conceived [3]. The idea was also described in the first patent of a contact lens [4]. Drug eluting contact lenses hold the promise of improved efficacy and compliance over existing delivery vehicles. Consequently, contact lenses for drug delivery remain a highly sought after innovation and hot-topic in research after 50 years[5]. In fact, 93% of eye care providers state that they would use a drug releasing contact lens upon the technology becoming available [6].


Current Therapies

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Currently eye drops are the primary method in ocular drug delivery and are used as the preferred vehicle for 90% of ophthalmic medications [7] [8]. Drugs are dissolved in aqueous solution and are delivered topically to the ocular surface into the inferior fornix of the conjunctiva. However, only a fraction of the drug dosage in eye drop is actually absorbed by the eye. One causative factor for this inefficiency is the low volume available on the surface of the eye. The conjunctival sac capacity is 15-30μL and the tear film volume is 7-8μL while the typical eye drop is 50-100μL. A portion of the drop goes into the cheek, another becomes available for systemic absorption from entry into the naso-lacrimal duct which frequently results in unwanted side-effects. Furthermore such noncorneal absorption as well as mechanical loss from tears and blinking and, only 1-7% of medication in the drop makes it through the cornea [9].

Furthermore the dose that is absorbed exhibits a pulse delivery mechanism. Initially, a short-lived overdose of medication is dispensed, then for a brief period therapeutic concentrations are delivered. Afterwards there is an extensive period characterized by sub-therapeutic levels until the next drop is administered.

Administration and compliance pose further problems; a typical example is glaucoma treatment. It has been well documented that 22-33% of patients administer their medications incorrectly. Likewise only 24-59% of ophthalmology patients are compliant in administering their drops [10] [11]

Ongoing Research

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For the past decade research has been ongoing on this topic.
Drug releasing contact lenses must not only have all the properties of a high-quality contact lens including:
-Optical clarity
-Specific refractive properties
-Comfort
-Biocompatibility
-Cost-effectiveness
-Amenability to storage
-Good shelf-life
The lenses must also have the ability to release one or more drug at therapeutic levels exhibiting zero-order release kinetics.This release mechanism must be harmless to the eye and minimize systemic effects.

There are two primary approaches to generating these drug eluting lenses. The first approach involves a lens manufactured with the drug sealed inside and the second involves loading drugs unto a pre-formed lens [12].

The Drug Loading Capacity of Conventional Lenses

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Conventional unmodified lenses such as hydroxyethyl methylacrylate (HEMA) hyrdrogel and the more modern silicon-hydrogel have the ability to absorb medication. HEMA hydrogel releases almost all of its drug mass in one day while silicon-hydrogel release only about 4-12% [13]. However, the release of the drug from the lens is characterized by a short burst followed by a period of underdosing only limited drug mass can be loaded unto these standard lenses.

Drugs Loaded Unto Pre-Formed Lenses

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Consequently traditional lenses have been modified to enhance their drug loading capacity and extend their drug release. HEMA hydrogel contact lenses have been modified with a methacrylated-derivative of β-cyclodextrin (β-CD) to enhance drug binding. Smaller drugs are released for periods up to 23 days, and larger drugs for up to 10 days [14]. Likewise, silicone hydrogel lenses have been modified so that a larger amount of drug is loaded and released. Also the solvent in which the drug is dissolved can affect loading capacity, ethanol allowed for a greater loading capacity in comparison to saline in silicon hyrdrogel lenses. Timolol or dexamethasone ethanolic solutions have each been released for over 150 days at a relatively constant rate after the initial burst [15].

Another modification applied to pre-formed lenses is the coating of the lens with drug containing liposomes [16] [17]. When applied topically drugs trapped in liposomes have been found to remain on the ocular surface for a longer period of time. Liposomes encapsulating lidocaine have been coated unto the surface of lenses and the drug mass was released over 6 days [18] [19].

Additionally, lenses with the ability to recognize particular compounds have been manufactured called molecularly imprinted contact lenses. These specialized lenses load greater than three times more drug and further prolong the duration of release in comparison to conventional lenses [20] [21]. Molecularly imprinted hydrogels have been found to release drugs between 2 [22] to 7 [23] days.

Lenses Manufactured with Drugs Trapped Inside

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Contact lenses have been manufactured with the drug mass trapped inside have a larger drug loading capacity and posses the ability to release drugs over a long period of time. Various substances have been integrated into the design of drug-eluting contact lenses, such as:

- Liposomes [24] - liposomes containing lidocaine, drug release spanned over a period of 6-7 days.

- Emulsions [25] - Oil-Surfactant Microemulsions loaded with lidocaine released drug mass over a period of 60 days.

- Surfactant Laden Hydrogels [26] - Cyclosporine A was loaded and released over a period of 29 days.

- Biomimetic Hydrogels [27] - These lenses are formed by the polymerization of monomers similar in structure to molecules which naturally bind the drug [28]. Lenses loaded with ketotifen can release the drug over a period of 7.5 days.

- Drug-Polymer Films Coated with HEMA Hydrogels [29] - A drug polymer film, made with the polymer Poly(lactic-co-glylic) acid (PGLA), was incorporated into a lens. Fluorescein and ciprofloxacin could be released over a period which spanned from weeks to months.

References

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  1. ^ Li, C., Modeling ophthalmic drug delivery by soaked contact lenses. Ind Eng Chem Res, 2006. 45: p. 3718–3724
  2. ^ Ciolino, J.B., C.H. Dohlman, and D.S. Kohane, Contact lenses for drug delivery. Semin Ophthalmol, 2009. 24(3): p. 156-60
  3. ^ Wichterle, O. and D. Lim, Hydrophilic Gels for Biological Use. Nature, 1960. 185(4706): p. 117-118
  4. ^ Wichterle, O., Cross-linked hydrophilic polymers and articles made therefrom. 1965
  5. ^ Ciolino, J.B., C.H. Dohlman, and D.S. Kohane, Contact lenses for drug delivery. Semin Ophthalmol, 2009. 24(3): p. 156-60
  6. ^ Wichterle, O., Hydrophilic gels for biological use. Nature, 1960. 185: p. 117-118
  7. ^ Bourlais, C.L., et al., Ophthalmic drug delivery systems--recent advances. Prog Retin Eye Res, 1998. 17(1): p. 33-58
  8. ^ Saettone, M., Progress and problems in ophthalmic drug delivery. Pharmatechnology, 2006: p. 1-6
  9. ^ Ghate, D. and H.F. Edelhauser, Barriers to glaucoma drug delivery. Journal of Glaucoma, 2008. 17(2): p. 147-156
  10. ^ Gurwitz, J.H., et al., Treatment for glaucoma: adherence by the elderly. Am J Public Health, 1993. 83(5): p. 711-6.
  11. ^ Rotchford, A.P. and K.M. Murphy, Compliance with timolol treatment in glaucoma. Eye (Lond), 1998. 12 ( Pt 2): p. 234-6.
  12. ^ Ciolino, J.B., C.H. Dohlman, and D.S. Kohane, Contact lenses for drug delivery. Semin Ophthalmol, 2009. 24(3): p. 156-60
  13. ^ Karlgard, C.C., L.W. Jones, and C. Moresoli, Ciprofloxacin interaction with silicon-based and conventional hydrogel contact lenses. Eye Contact Lens, 2003. 29(2): p. 83-9
  14. ^ dos Santos, J.F., et al., Poly(hydroxyethyl methacrylate-co-methacrylated-beta-cyclodextrin) hydrogels: synthesis, cytocompatibility, mechanical properties and drug loading/release properties. Acta Biomater, 2008. 4(3): p. 745-55
  15. ^ Kim, J., A. Conway, and A. Chauhan, Extended delivery of ophthalmic drugs by silicone hydrogel contact lenses. Biomaterials, 2008. 29(14): p. 2259-69
  16. ^ Danion, A., I. Arsenault, and P. Vermette, Antibacterial activity of contact lenses bearing surface-immobilized layers of intact liposomes loaded with levofloxacin. J Pharm Sci, 2007. 96(9): p. 2350-63
  17. ^ Danion, A., et al., Fabrication and characterization of contact lenses bearing surface-immobilized layers of intact liposomes. J Biomed Mater Res A, 2007. 82(1): p. 41-51
  18. ^ Danion, A., I. Arsenault, and P. Vermette, Antibacterial activity of contact lenses bearing surface-immobilized layers of intact liposomes loaded with levofloxacin. J Pharm Sci, 2007. 96(9): p. 2350-63
  19. ^ Danion, A., et al., Fabrication and characterization of contact lenses bearing surface-immobilized layers of intact liposomes. J Biomed Mater Res A, 2007. 82(1): p. 41-51
  20. ^ Hiratani, H., Y. Mizutani, and C. Alvarez-Lorenzo, Controlling drug release from imprinted hydrogels by modifying the characteristics of the imprinted cavities. Macromol Biosci, 2005. 5(8): p. 728-33
  21. ^ Hiratani, H., et al., Ocular release of timolol from molecularly imprinted soft contact lenses. Biomaterials, 2005. 26(11): p. 1293-8
  22. ^ Hiratani, H., et al., Ocular release of timolol from molecularly imprinted soft contact lenses. Biomaterials, 2005. 26(11): p. 1293-8
  23. ^ Ali, M., et al., Zero-order therapeutic release from imprinted hydrogel contact lenses within in vitro physiological ocular tear flow. J Control Release, 2007. 124(3): p. 154-62
  24. ^ Gulsen, D., C.C. Li, and A. Chauhan, Dispersion of DMPC liposomes in contact lenses for ophthalmic drug delivery. Curr Eye Res, 2005. 30(12): p. 1071-80
  25. ^ Li, C.C., et al., Timolol transport from microemulsions trapped in HEMA gels. J Colloid Interface Sci, 2007. 315(1): p. 297-306
  26. ^ Kapoor, Y. and A. Chauhan, Drug and surfactant transport in Cyclosporine A and Brij 98 laden p-HEMA hydrogels. J Colloid Interface Sci, 2008. 322(2): p. 624-33
  27. ^ Venkatesh, S., S.P. Sizemore, and M.E. Byrne, Biomimetic hydrogels for enhanced loading and extended release of ocular therapeutics. Biomaterials, 2007. 28(4): p. 717-24
  28. ^ Venkatesh, S., et al., Applications of biomimetic systems in drug delivery. Expert Opin Drug Deliv, 2005. 2(6): p. 1085-96
  29. ^ Venkatesh, S., et al., Applications of biomimetic systems in drug delivery. Expert Opin Drug Deliv, 2005. 2(6): p. 1085-96
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