Iontophoresis enhances voriconazole antifungal potency and corneal penetration.


Gelfuso GM, Ferreira-Nunes R, Dalmolin LF, Dos S Ré AC, Dos Santos GA, A P de Sá F, Cunha-Filho M, Alonso A, Mendanha Neto SA, L V Anjos J, Aires CP, F V Lopez R, Gratieri T.
Int J Pharm. 2019 Dec 26:118991.


Strategies to enhance corneal penetration of voriconazole (VOR) could improve the treatment of fungal keratitis. Here, we evaluated the use of iontophoresis for ocular VOR delivery from either: (i) a cyclodextrin inclusion complex (CD VOR), (ii) a liposome (LP VOR), and (iii) a chitosan-coated liposome (LP VOR CS). LP VOR CS presented mean diameter of 139.2 ± 1.3 nm and zeta potential equal to + 3.3 ± 1.5 mV compared to 134.6 ± 1.7 and -8.2 ± 3.0 mV of LP VOR, which, together with mucin mucoadhesion study, confirmed chitosan-coating. Both drug and liposomal formulations were stable under the influence of an applied electric current. Interestingly, in vitro studies in Candida glabrata culture indicated a decrease in VOR MIC values following iontophoresis (from 0.28 to 0.14 µg/mL). Iontophoresis enhanced drug penetration into the cornea. After 10 min of a 2 mA/cm2 applied current, corneal retained amounts were 45.4 ± 11.2, 30.4 ± 2.1 and 30.6 ± 2.9 µg/cm2 for, respectively, CD VOR, LP VOR, and LP VOR CS. In conclusion, iontophoresis increases drug potency and enhances drug penetration into the cornea, showing potential to be used as "an emergency burst delivery approach".