Ocular Disposition, Pharmacokinetics, Efficacy and Safety of Nanoparticle-Formulated Ophthalmic Drugs

Abstract

Ophthalmic drugs are delivered to ocular tissues predominantly via relatively simple formulations, such as topically dosed water-soluble drug solutions and water-insoluble drug suspensions in ointments. An ideal topical drug delivery system should possess certain desirable properties, such as good corneal and conjunctival penetration, prolonged precorneal residence time, easy instillation, non-irritative and comfortable to minimize lachrymation and reflex blinking, and appropriate rheological properties. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. To improve ocular bioavailability of topically dosed ophthalmic drugs, a variety of ocular drug delivery systems, such as hydrogels, microparticles, nanoparticles, microemulsions, liposomes and collagen shields, have been designed and investigated. These newer systems may, to some extent, control drug release and maintain therapeutic levels in ocular tissues over a prolonged period of time. This review focuses on the in vitro, ex vivo and in vivo studies of ophthalmic drugs formulated in nanoparticles published over the past two decades. The progress and development issues relating to ocular disposition, pharmacokinetics, efficacy and safety of the nanoparticle-formulated ophthalmic drugs are specifically addressed. Information and discussions summarized in this review are helpful for pharmaceutical scientists to develop better ophthalmic therapeutics.

A Nonionic Surfactant/Chitosan Micelle System in an Innovative Eye Drop Formulation

“…Although Caco-2 cells are of intestinal origin, they have been used to study more general membrane effects of drug delivery systems intended for ocular administration. [31][32][33] Figure 2 shows the results of the transport studies of DEX from the F127/CH micelle systems across Caco-2 cell monolayers at pH 4.5. The duration of the DEX transport experiments was 3 h, because a longer retention of delivery systems at the ocular surface cannot be expected due to precorneal loss factors.…”

Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

“…The dual nature of the cornea acts as a strong barrier to drugs, which protects the ocular globe. 10,11 Therefore, enhancing the ocular penetration of eye drops remains one of the most challenging goals of ophthalmology. 12 Over the past few decades, the use of polymeric nanomicelles that can self-assemble from amphiphilic block copolymers as delivery vehicles for the controlled delivery and solubilization of water-insoluble drugs has been the focus of increasing interest.…”

Biomechanical Strengthening of the Human Cornea Induced by Nanoplatform-Based Transepithelial Riboflavin/UV-A Corneal Cross-Linking

“…The biodegradable polymeric 2-hydroxypropyl-b-cyclodextrin nanoparticles act as carrier molecules to enhance the solubility and bioavailability of active molecules, such as riboflavin. [23][24][25][26] Because b-cyclodextrins are hydrophobic inside and hydrophilic outside, they form complexes with riboflavin and facilitate its diffusion through the epithelium. In addition, EDTA and trometamol were added to the solution as enhancers in order to loosen the epithelial tight junctions and further improve the penetration of riboflavin in the stroma through the intact epithelium.…”