Ultra-small micelles based on polyoxyl 15 hydroxystearate for ocular delivery of myricetin: optimization, in vitro, and in vivo evaluation.

The aim was to develop a nanocarrier based on polyoxyl 15 hydroxystearate (Kolliphor® HS15, HS15) micelles for the solubility, stability, and ocular delivery of myricetin (Myr). An optimized ratio of HS15 and Myr was prepared to fabricate HS15-Myr micelle ophthalmic solution. Myr-encapsulating HS15 micelles (HS15-Myr micelles) were subjected to physicochemical characterizations. The chemical stability of Myr in HS15 micelles and storage stability of HS15-Myr micelle ophthalmic solutions were evaluated. In vitro parallel artificial membrane permeability assay and antioxidant activity of Myr in HS15 micelles were also measured. In vivo ocular tolerance, corneal permeation, and anti-inflammatory efficacy studies were conducted following ocular topical administration. HS15-Myr micelles were successfully prepared and presented transparent appearance with high encapsulation (96.12 ± 0.31%), ultra-small micelle size (a mean diameter of 12.17 ± 0.73 nm), uniform size distribution (polydispersity index [PDI] = 0.137 ± 0.013), and negative surface charge (- [4.28 ± 0.42] mV). Myr in HS15 micelle solution demonstrated higher aqueous stability than the free Myr solution among the accepted pH range for eyedrops. HS15-Myr micelle ophthalmic solution demonstrated high storage stability at 4 °C and 25 °C. HS15 micelles could significantly improve in vitro antioxidant activity and faster membrane permeation of Myr. No irritations or corneal damage were revealed in rabbit eyes after ocular administration of HS15-Myr micelle solution. In vivo corneal permeation study demonstrated that HS15-Myr micelles could penetrate the cornea efficiently in mouse eyes. Further, HS15-Myr micelles also demonstrated significant in vivo anti-inflammatory activity. It can be concluded that HS15 micelles are a potential ophthalmic delivery nanocarrier for poorly soluble drugs such as Myr.

QobuR - A new in vitro human corneal epithelial model for preclinical drug screening.

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm2 at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. We found that some of the Non-Irritant products evaluated still damage the corneal epithelial integrity and current protocols for ocular irritancy should therefore include a barrier integrity evaluation. Moreover, in order to comprehensively evaluate corneal permeability of the active ingredients, we propose the use of QobuR as an all-in-one alternative method for evaluating ocular irritancy, barrier disruptions and permeability rates of topically applied ocular drugs to improve current in vitro drug testing procedures.

Evaluating the novel application of cyclosporine 0.1% in ocular surface disease.

INTRODUCTION: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient's visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD. Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation. Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.

[Preparation and evaluation in vivo of Scutellaria thermosensitive gel].

OBJECTIVE: To study scutellaria thermosensitive gel in situ. METHOD: The phase transition temperature of gel with various concentration polymer solutions was studied by using stirring method and the viscosity of gel was monitored under different temperatures. Eye irritation experiments were performed with rabbit. The duration of residence time in rabbit eyes of scutellaria thermosensitive gel was observed with 2% fluorescein. RESULT: 20% poloxmar407 and 10% poloxmar 188 were suitable to scutellaria thermosen-sitive gel in situ. The results suggested that the scutellaria thermosensitive gel in situ based on poloxmar were nonirritant and retention time on the surface of eye was (150 +/- 8) min. CONCLUSION: The scutellaria thermosensitive gel in situ forms gel in eye and has longer release time than that of eye drops.

Localization of local anesthetic solution by magnetic resonance imaging.

PURPOSE: The aim of this study was to examine the distribution of local anesthetic solution by magnetic resonance imaging (MRI) after combined peribulbar and retrobulbar, superomedial retrobulbar, and sub-Tenon's injection in relation to clinical akinesia. DESIGN: Randomized clinical trial. PARTICIPANTS: Fifteen patients scheduled for cataract surgery, 5 patients in each group. METHODS: Five patients received combined peribulbar and retrobulbar anesthesia, 5 patients received superomedial retrobulbar injection, and 5 patients had sub-Tenon's injection, all with a combination of bupivacaine 0.75%, lidocaine 2%, and hyaluronidase. The MRI scans were performed before the injection and up to 35 minutes after the injection. RESULTS AND CONCLUSIONS: Reliable anesthesia is achieved using a combined peribulbar and retrobulbar block and a relatively great volume of local anesthetic solution, which spreads throughout the orbit, as evidenced by MRI. After superomedial retrobulbar and sub-Tenon's injection, the local anesthetic solution accumulates behind the globe. Sub-Tenon's injection gives good analgesia and slight akinesia with a very small volume. Superomedial retrobulbar injection and combined peribulbar and retrobulbar block provide a similar degree of exophthalmos, which seems to be the result of the volume injected behind the globe.