Thermosensitive and mucoadhesive in situ ocular gel for effective local delivery and antifungal activity of itraconazole nanocrystal in the treatment of fungal keratitis

Andi Dian Permana, Rifka Nurul Utami, Patricia Layadi, Achmad Himawan, Nana Juniarti, Qonita Kurnia Anjani, Emilia Utomo, Sandra Aulia Mardikasari, Andi Arjuna, Ryan F Donnelly

Research output: Contribution to journalArticlepeer-review

Abstract

Itraconazole is a lipophilic drug, which limits its absorption for ocular administration. This study focused on the incorporation of itraconazole into nanocrystalline carrier system with stabilizer Pluronic® F127 and was further formulated into thermosensitive in situ ocular gel. Itraconazole nanocrystals (ITZ-NCs) were fabricated using media milling method with ultra-small-scale device. The obtained nanocrystals were observed to have a better in vitro activity against C. albicans (CA) compared to free itraconazole suspension in water. Furthermore, the optimization of the thermosensitive ocular gel formula was carried out with a central composite design, using three types of polymers, namely Pluronic® F127, Pluronic® F68, and hydroxypropyl methylcellulose (HPMC). After being dispersed into the optimized thermosensitive gel base, ITZ-NCs did not alter in terms of physical characteristics. Ex vivo ocularkinetic studies on infected porcine eye models showed a better profile of the optimized formula of thermosensitive in situ ocular gel when compared to standard gel base. Importantly, the ex vivo antifungal activity of these preparations was also increased, with a 93% decrease in the CA population observed after 48 h in infected porcine eye model. Altogether, this work has provided evidence of a novel approach in developing more advanced treatments for fungal keratitis.
Original languageEnglish
Article number120623
JournalInternational journal of pharmaceutics
Volume602
Early online date21 Apr 2021
DOIs
Publication statusPublished - 01 Jun 2021

Keywords

  • Antifungal
  • Fungal keratitis
  • Itraconazole
  • Mucoadhesive
  • Nanocrystals
  • Thermosensitive in situ ocular gel

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