Topical semifluorinated alkane-based azithromycin suspension for the management of ocular infections.

The management of ocular infections is challenging due to poor drug bioavailability and vehicle related adverse effects associated with current antibiotic eye drops. Semifluorinated alkanes (SFAs) are reportedly well-tolerated on the ocular surface and can enhance ocular drug bioavailability. Therefore, an SFA-based azithromycin suspension (SFA-AZM) was prepared and its antibacterial efficacy was compared to that of marketed azithromycin eye drops by monitoring the growth of bioluminescent Staphylococcus aureus in ex vivo ocular tissues. Corneal and conjunctival distribution of hydrophobic fluorescent dye particles from an SFA suspension (SFA-BODIPY) resulted in preferential dye localisation in the epithelial layers of both tissues. However, corneal dye absorption was significantly lower than conjunctival absorption, likely due to limited adhesion of suspended dye particles to the corneal compared to the conjunctival epithelium. In line with the dye distribution results, bacterial colonisation in the conjunctiva reduced significantly upon application of SFA-AZM with the efficacy being greater than or at least equal to the marketed azithromycin eye drops. In the cornea, all tested azithromycin eye drops reduced the rate of bacterial growth with similar efficacy. Overall, the SFA-AZM suspension tested here may provide a safe and effective alternative for the management of ocular infections by enhancing conjunctival drug absorption and thus drug efficacy.

Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics.

PURPOSE: Dry eye disease (DED) is one of the most prevalent ocular surface disorders that presents clinically. Recently, the semifluorinated alkane (SFA) perfluorohexyloctane (NovaTears®; EvoTears®) entered the market for the management of evaporative DED, while perfluorobutylpentane has been used as a vehicle to enhance ocular drug delivery. This study evaluated the mechanisms by which SFAs might improve therapeutic outcomes in DED. METHODS: Interactions of both SFAs with the corneal surface were evaluated ex vivo using high-speed photography. The in vivo influence of SFAs on tear fluid dynamics was evaluated in healthy rabbit eyes observing changes in lipid layer grade, tear evaporation rate, tear volume and tear osmolarity. Furthermore, ocular tolerability was confirmed by clinical scoring and sodium fluorescein staining. RESULTS: Ex vivo studies demonstrated that both SFAs rapidly spread on the ocular surface with their contact angle on the cornea being virtually zero. A significant improvement in lipid layer grade was observed immediately after instillation of both SFAs in vivo, although the improvement was more sustained upon instillation of perfluorohexyloctane with a statistically significant difference compared to saline instillation evident from day five onwards. No significant changes in tear evaporation rate, volume or osmolarity, nor any signs of ocular irritation were observed after application of either SFA over the seven-day study period. CONCLUSION: Both SFAs showed excellent spreading on the ocular surface. Perfluorohexyloctane improved the lipid layer grade significantly after topical application supporting its potential to stabilise the tear film lipid layer and thus provide symptomatic relief in evaporative DED.