Impact of amphotericin B aggregation state in the loading and release kinetics in contact lenses

Introduction: Keratitis is an inflammation of the cornea that can have infectious or non-infectious origins [1]. While most infectious keratitis cases are caused by bacteria, those caused by fungi and amoebas have a more insidious nature and are difficult to treat, often requiring prolonged therapy and frequent debridement [2, 3]. Amphotericin B (AmB) is one of the most effective drugs for fungal infections, however, its poor water solubility limits its use for ophthalmic applications [4]. The aim of this work focused on investigating the loading and release kinetics of AmB on commercially available contact leases with three different compositions.
Methods: AmB was formulated in two different aggregation state, monomer and dimer [4]. The loading and sustained release kinetics of AmB in three different aggregation states were tested on contact lenses with different composition. Conventional hydrogels were tested such as nelfilcon A (Dailies aquacomfort Plus), omafilcon A (Proclear) and delefilcon A (Dailies Total).
Results: AmB was successfully formulated as a monomeric and dimeric aggregation state which was demonstrated due to its characteristic yellowish and orangish transparent coloured solutions respectively as well as for its well defined bands in the UV spectrophotometer, 363- 383 and 406 nm for the monomer and 328nm for the dimer [5]. The solubilization of AmB into the monomeric form resulted in a 4-fold lower AmB concentration in aqueous media. This difference in concentration gradient can explain the drug loading kinetics between the dimer and the monomer (Fig. 1). Significant differences were observed among the drug loading in the three commercial contact lenses. The dimer showed 10-fold higher diffusion rates (above 100 μg per lense) compared to the monomer in Proclear contact lenses that were the ones with the highest drug loading followed by Dailies Total and Aquacomfort Plus. The release kinetics of dimeric AmB from loaded contact lenses (Proclear) showed a sustained release for over 3 h which can be advantageous to keep efficacious concentration in the eye for prolonged periods compared to conventional eye drops formulations.
Conclusions/Implications: AmB has exhibited a high drug loading efficiency in Proclear contact lenses fabricated from Omalficon A polymer. Drug loading was superior to 100 μg/lenses and the release in aqueous media was sustained over 3 h being which is advantageous compared to an eye drop formulation.