Effect of drug solubility on transscleral drug delivery

Transscleral drug delivery has emerged as an attractive method for treating posterior segment eye disorders due to its less invasive, large scleral surface, and good capability for targeted drug delivery.However, in the clinical retina of posterior segment diseases, transscleral drug delivery is less efficient than intravitreal injection.This is due to the fact that drug is subjected to the multiple barriers before crossing into retina or vitreous, such as the sclera, choroid, retinal pigment epithelium, and even the counter-directional intraocular pressure and the associated fluid movement as well as choroidal circulation.At the same time, the properties of the drug itself, such as water solubility, dissolution rate, molecular weight and radius, and hydrophobicity also significantly affect the drug crossing into retina.Out of these factors, water solubility is the key factor for optimal transscleral drug delivery to achieve greater retina bioavailability.When a drug has high water solubility and applied to sclera surface, high local drug concentration will be absorbed into systemic circulation and cause side effects; when a drug has very limited water solubility, local drug concentration on the sclera cannot reach a high enough concentration gradient across the sclera and choroid, therefore the limited available drug will be cleared by the blood and lymphatic circulation of the conjunctiva and episcleral tissues.Therefore, water solubility has become a good venue for scientists to develop various formulations to improve the solubility and the delivery efficiency for transscleral drug delivery.The drugs which can be utilized to treat chorioretinal diseases are often of hydrophobicity or low water solubility.These drugs can be formulated into various suspensions with the help of altered crystallinity, addition of excipient, or solubility promoting agents, as well as various particulates, such as liposomes or nanoparticles to optimize the drug solubility or dissolution rate.Therefore, increasing the solubility of poorly soluble drugs is a commonly used means of developing transscleral drug delivery formulations to promote drug penetration into the sclera.In this review, we synthesized the updated information regarding effect of drug solubility on transscleral drug delivery in hope that the article will benefit both basic and clinical researches for further exploration of transscleral drug delivery.