Delivery of therapeutics for deep-seated ocular conditions – status quo

Abstract

Objectives There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Key findings Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Summary Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance.

Lipid-Based Nanocarriers as Topical Drug Delivery Systems for Intraocular Diseases

“…This route involves drug delivery through systemic circulation, crossing all the way to the blood–ocular barriers, including the blood–aqueous barrier and the blood–retinal barrier. Although the extent of the drug to the retina could be improved through this route, the presence of the blood–ocular barriers offers a rigorous permeability regulation in drug delivery to this area, presenting an approximate bioavailability of 2% to the intraocular tissue [ 12 , 22 , 52 ].…”

Hyaluronic Acid-Based Gold Nanoparticles for the Topical Delivery of Therapeutics to the Retina and the Retinal Pigment Epithelium

“…The posterior segment of the eye comprises the sclera, the retina, the choroid, the optic nerve, and the vitreous humor. This part of the eye is susceptible to several disorders and diseases that often lead to irritation, visual impairment, and even vision loss, such as glaucoma, age-related macular degeneration, and retinopathy [ 1 ]. Low bioavailability from systemic administration has made delivering drugs to the retina challenging due to various ocular barriers [ 2 , 3 , 4 , 5 ], hindering penetration to the posterior segment of the eye.…”

Retina-Targeted Delivery of 17β-Estradiol by the Topically Applied DHED Prodrug

“…While topical application of ophthalmic agents (especially for the treatment of the posterior segment of the eye) have numerous limitations including low ocular bioavailability and systemic drug absorption leading to unwanted adverse effects [28], patients prefer this route of Figure 1. 10β,17β-dihydroxyestra-1,4-dien-3-one (DHED) is a bioprecursor prodrug converted to 17β-estradiol (E2) in neuronal environments through NADPH-dependent enzymatic reduction [22,23].…”

“…While topical application of ophthalmic agents (especially for the treatment of the posterior segment of the eye) have numerous limitations including low ocular bioavailability and systemic drug absorption leading to unwanted adverse effects [28], patients prefer this route of administration to invasive injections [29]. DHED also appears ideal in size and lipophilicity for the transcorneal route of drug absorption [28,29].…”

“…While topical application of ophthalmic agents (especially for the treatment of the posterior segment of the eye) have numerous limitations including low ocular bioavailability and systemic drug absorption leading to unwanted adverse effects [ 28 ], patients prefer this route of administration to invasive injections [ 29 ]. DHED also appears ideal in size and lipophilicity for the transcorneal route of drug absorption [ 28 , 29 ]. Along with comparative characterization of corneal permeability and in vitro metabolism in ocular tissues, we also provide in vivo evidence here for the retina-selective formation of E2 from this bioprecursor prodrug when it is applied topically in eye drops to rats and rabbits.…”