Recent Advances in the Design of Topical Ophthalmic Delivery Systems in the Treatment of Ocular Surface Inflammation and Their Biopharmaceutical Evaluation

Abstract

Ocular inflammation is one of the most common symptom of eye disorders and diseases. The therapeutic management of this inflammation must be rapid and effective in order to avoid deleterious effects for the eye and the vision. Steroidal (SAID) and non-steroidal (NSAID) anti-inflammatory drugs and immunosuppressive agents have been shown to be effective in treating inflammation of the ocular surface of the eye by topical administration. However, it is well established that the anatomical and physiological ocular barriers are limiting factors for drug penetration. In addition, such drugs are generally characterized by a very low aqueous solubility, resulting in low bioavailability as only 1% to 5% of the applied drug permeates the cornea. The present review gives an updated insight on the conventional formulations used in the treatment of ocular inflammation, i.e., ointments, eye drops, solutions, suspensions, gels, and emulsions, based on the commercial products available on the US, European, and French markets. Additionally, sophisticated formulations and innovative ocular drug delivery systems will be discussed. Promising results are presented with micro- and nanoparticulated systems, or combined strategies with polymers and colloidal systems, which offer a synergy in bioavailability and sustained release. Finally, different tools allowing the physical characterization of all these delivery systems, as well as in vitro, ex vivo, and in vivo evaluations, will be considered with regards to the safety, the tolerance, and the efficiency of the drug products.

Self-Assembling Tacrolimus Nanomicelles for Retinal Drug Delivery

“…There was no significant difference observed in the transport of TAC-NMF at 3 and 6 h ( Figure 12 ), but at 9 and 12 h, the transport of TAC-NMF was significantly higher than TAC group. TAC-NMF crossed the CCL 20.2 cell monolayer by paracellular route, which enabled its active absorption into D407 cells in the bottom chamber [ 51 , 52 , 53 ]. This can suggest that a nanomicellar system consisting of a mixture of amphiphilic polymers such as HCO-40 and OC-40 can be useful for the ophthalmic delivery of hydrophobic drugs such as tacrolimus to the back of the eye via the transscleral route.…”

“…This can suggest that a nanomicellar system consisting of a mixture of amphiphilic polymers such as HCO-40 and OC-40 can be useful for the ophthalmic delivery of hydrophobic drugs such as tacrolimus to the back of the eye via the transscleral route. In addition, a lower CMC and controlled release of tacrolimus from the nanomicellar core can aid the effective delivery of TAC-NMF to the back of the eye via the conjunctival-scleral pathway for retinal disorders absorption into D407 cells in the bottom chamber [51][52][53]. This can suggest that a nanomicellar system consisting of a mixture of amphiphilic polymers such as HCO-40 and OC-40 can be useful for the ophthalmic delivery of hydrophobic drugs such as tacrolimus to the back of the eye via the transscleral route.…”

Assessment of In-Situ Gelling Microemulsion Systems upon Temperature and Dilution Condition for Corneal Delivery of Bevacizumab

“…That being said, the topical application of BVZ seems to be a non-invasive and practical procedure to treat several anterior segment diseases; however, there are some disadvantages that cannot be underestimated when common eye-drops are administered, such as the poor ocular bioavailability, due to high tear-fluid turnover rate and high nasolacrimal drainage. Novel ocular drug delivery approaches, including nanomicelles, nanoparticles [ 22 ], drug-eluting contact lenses, ocular inserts, ocular iontophoresis and ocular devices that prolong precorneal residence and enhance the bioavailability of the therapeutic agent are under study [ 23 , 24 , 25 ]. The primary goal of any ophthalmic topical drug delivery system is to improve the precorneal residence time, maintain a therapeutic drug concentration level at the target site, reduce the frequency of administration and overcome the various ocular barriers.…”

Ocular Delivery of Polyphenols: Meeting the Unmet Needs

“…The eye functions as a separate unit since it is protected from molecules circulating in the peripheral blood system through the blood-aqueous and blood-retinal barriers. Under ocular inflammatory conditions, the structural integrity of these barriers can be compromised, resulting in the further tissue infiltration of immune cells and the production of high levels of inflammatory mediators [ 39 , 40 , 41 ].…”