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Development of itraconazole ocular delivery system using β-cyclodextrin complexation incorporated into dissolving microneedles for potential improvement treatment of fungal keratitis.
- Source :
-
Journal of biomaterials science. Polymer edition [J Biomater Sci Polym Ed] 2024 Oct; Vol. 35 (15), pp. 2315-2342. Date of Electronic Publication: 2024 Jul 31. - Publication Year :
- 2024
-
Abstract
- Itraconazole (ITZ) is one of the broad-spectrum antifungal agents for treating fungal keratitis. In clinical use, ITZ has problems related to its poor solubility in water, which results in low bioavailability when administered orally. To resolve the issue, we formulated ITZ into the inclusion complex (ITZ-IC) system using β-cyclodextrin (β-CD), which can potentially increase the solubility and bioavailability of ITZ. The molecular docking study has confirmed that the binding energy of ITZ with the β-CD was -5.0 kcal/mol, indicating a stable conformation of the prepared inclusion complex. Moreover, this system demonstrated that the inclusion complex could significantly increase the solubility of ITZ up to 4-fold compared to the pure drug. Furthermore, an ocular drug delivery system was developed through dissolving microneedle (DMN) using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as polymeric substances. The evaluation results of DMN inclusion complexes (ITZ-IC-DMN) showed excellent mechanical strength and insertion ability. In addition, ITZ-IC-DMN can dissolve rapidly upon application. The ex vivo permeation study revealed that 75.71% (equivalent to 3.79 ± 0.21 mg) of ITZ was permeated through the porcine cornea after 24 h. Essentially, ITZ-IC-DMN exhibited no signs of irritation in the HET-CAM study, indicating its safety for application. In conclusion, this study has successfully developed an inclusion complex formulation containing ITZ using β-CD in the DMN system. This approach holds promise for enhancing the solubility and bioavailability of ITZ through ocular administration.
- Subjects :
- Animals
Drug Delivery Systems
Swine
Cornea metabolism
Cornea drug effects
Administration, Ophthalmic
Molecular Docking Simulation
Biological Availability
Povidone chemistry
Polyvinyl Alcohol chemistry
beta-Cyclodextrins chemistry
Itraconazole chemistry
Itraconazole administration & dosage
Itraconazole pharmacology
Itraconazole pharmacokinetics
Keratitis drug therapy
Solubility
Antifungal Agents pharmacology
Antifungal Agents chemistry
Antifungal Agents administration & dosage
Needles
Subjects
Details
- Language :
- English
- ISSN :
- 1568-5624
- Volume :
- 35
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Journal of biomaterials science. Polymer edition
- Publication Type :
- Academic Journal
- Accession number :
- 39083398
- Full Text :
- https://doi.org/10.1080/09205063.2024.2380129