Aqueous eye drops containing drug/cyclodextrin nanoparticles deliver therapeutic drug concentrations to both anterior and posterior segment

Abstract

Using topical application to deliver therapeutic concentrations of drugs to the posterior segment of the eye remains very challenging. As a result, posterior segment diseases are usually treated by intravitreal injection or implant. While topical treatments are commonly used for anterior segment conditions, they sometimes require frequent applications. Eye drop formulations based on γ‐cyclodextrin (γCD)‐based nanoparticle aggregates were developed, which in animal models and clinical studies deliver therapeutic concentrations of drugs (dorzolamide and dexamethasone) to both anterior and posterior segments of the eye. An early study in humans showed dorzolamide/γCD eye drops could achieve comparable intraocular pressure decreases to commercial dorzolamide eye drops, but with less frequent application. Pilot studies with dexamethasone/γCD eye drops suggested that they could be effective in a range of conditions, including diabetic macular oedema, cystoid macular oedema and vitritis secondary to uveitis, postcataract surgery inflammation and postoperative treatment in trabeculectomy. Phase II studies with similar dexamethasone/γCD nanoparticle eye drops in diabetic macular oedema and postcataract surgery inflammation have recently been completed. This technology has the potential to be used with other classes of drug molecules and to replace or complement invasive treatments, providing safer, non‐invasive therapies, particularly for posterior segment conditions, that can be self‐administered as eye drops by patients.

Novel Eye Drop Delivery Systems: Advance on Formulation Design Strategies Targeting Anterior and Posterior Segments of the Eye

“…An important obstacle facing the drug at this point is tear turnover. Normally, the tear film has a volume of approximately 7-9 µL, a thickness of approximately 7-10 µm, and a turnover rate between 0.5 and 2.2 µL/min [14]. The sudden increase in tear film volume leads to an increase in tear film turnover rate and rapid clearance of drug molecules through tear drainage within minutes.…”

“…The superficial corneal epithelium makes up six to eight layers of cells with a total thickness of approximately 40-50 µm. The epithelium cell becomes flattened during maturation and eventually forms tight intercellular junctions, which allow the permeation of hydrophilic drugs at a rate of only 10 −7 -10 −5 cms −1 [14]. The hydrophilic matrix next to the corneal epithelium (approximately 80% water content) has a thickness of approximately 450-500 µm, representing 90% of the corneal thickness, and in turn imposes significant limitations on lipophilic drugs due to solubility and partition coefficients [23].…”

“…Ointments are not commonly used to treat ocular diseases, because the oil components can affect vision for some time after application. The absorption of these traditional eye drops on the outer surface of the eye is limited by different barriers such as static (corneal and blood-aqueous barrier (BAB)), dynamic (tear drainage, conjunctival blood, and lymphatic flow), and metabolic barriers [11], making the bioavailability of the drug after topical administration very low (<5% of the administered dose) [14] and difficult to be delivered to the posterior segment of the eye.…”

Topical Drug Delivery to the Posterior Segment of the Eye

“…In a clinical trial with DME patients, this formulation could significantly improve visual acuity and result in decreased macular thickness, comparable to a posterior subtenon injection of triamcinolone acetonide, a frequently-reported, off-label treatment for DME [140]. Several other clinical studies using γCD eye drops have been conducted, and the development is ongoing to find better treatment options for DME and postcataract surgery inflammation [141].…”

Cyclodextrin Derivative Enhances the Ophthalmic Delivery of Poorly Soluble Azithromycin

“…These technologies have the potential to be used with other classes of drug molecules and to replace or complement invasive treatments, providing safer, non-invasive therapies, particularly for posterior segment conditions that can be self-administered as eye drops by patients. 22 In fact, another group had prepared an in situ gel for ophthalmic preparation containing ciprofloxacin hydrochloride, which was successfully formulated as in situ gel-forming eye drops with the help of sodium alginate and hydroxypropyl methylcellulose (HPMC). 23 These results demonstrated that the alginate and HPMC mixture could be used as in situ gelling carriers to improve ocular bioavailability and patient compliance.…”