Ocular drugs are administered by systemic, topical, subconjunctival, intravitreal, and intrascleral delivery.
1–4 Some of these methods are invasive as they may require a needle to penetrate the eye tissue or may require long-term regimen treatments,
1,5 increasing the likelihood of patient non-compliance and leading to lower treatment success rates.
6 The primary method of ocular drug delivery is topical administration, with the cornea being the preferred route despite its small surface area and low permeability.
7–9 Eye drops are noninvasive, easily administered to the cornea, and accessible to a broad patient population.
1,5,10 However, topical eye drops suffer from limited small molecule diffusion across the cornea, resulting in a low bioavailability of approximately 1% to 7% foA2Ar most US Food and Drug Administration (FDA)-approved eye drugs.
4 The bioavailability of macromolecules, including antibodies and proteins, is significantly lower (<1%).
7,10 Topical ocular medications are usually wasted away by normal tear volume, blinking, and induced lacrimation factors.
10 Ocular delivery is a significant challenge due to multiple eye barriers.
1,5,10 These barriers in the path to successful drug delivery are classified as static or dynamic.
11,12 Static barriers include the corneal epithelium, stroma, endothelium, and blood-aqueous barrier. Dynamic barriers include tear dilution, the conjunctival barrier, and the retinal-blood barrier. The unique structural differences of tissues in the cornea, conjunctiva, retina, and sclera block penetration by toxins, small molecules, viruses, infectious microorganisms, and macromolecules.
13,14 The clinical need is to minimize the time of barrier recovery while maximizing the bioavailability of the administered drug.
15,16 For example, peptide drugs, such as cyclosporine, growth factors, interferons, and interleukins demonstrated treatment of uveitis, corneal wound healing, corneal herpes simplex infections, and modification of ocular immune response. However, most peptide drugs are impermeable when applied topically to the eye due to their high molecular weight.
17 A practical and noninvasive macromolecule delivery method is needed to treat various anterior segment ocular diseases.
4