Posaconazole (PSC), a broad-spectrum triazole antifungal agent, holds significant potential in treating ocular fungal infections such as keratitis and sclerokeratitis. Despite its clinical efficacy, the lack of a commercially available ocular formulation limits its application. Currently, off-label use of diluted oral suspension (Noxafil®) is practiced, but this approach suffers from extremely low ocular bioavailability due to PSC’s highly lipophilic nature (LogP = 5.5). This study investigates a novel micellar delivery system composed of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), a non-ionic surfactant with favorable biocompatibility and solubilizing properties. The optimized TPGS-based micelles were evaluated for ex vivo permeation across bovine cornea and sclera, penetration into ocular tissues, antifungal activity against Candida albicans, and ocular safety via the Hen’s Egg Test-Chorioallantoic Membrane (HET-CAM) assay.RPL18A Antibody Formula
Ex vivo permeation studies revealed that PSC-loaded micelles significantly enhanced drug transport compared to the Noxafil® suspension. The apparent corneal permeability coefficient (Papp) of NM-51F micelles reached 2.6076 × 10⁻³ cm/s, surpassing that of Noxafil® by over 250-fold. Similarly, scleral permeation was enhanced up to 56-fold. These results indicate that micellar carriers effectively bypass ocular barriers—particularly the corneal epithelium and tight junctions—due to their nanoscale size (<15 nm) and ability to improve drug solubility. The sustained release profile observed in prior studies further supports prolonged contact time with target tissues, enhancing therapeutic efficacy. Penetration studies confirmed higher accumulation of PSC in both cornea (66.79 ± 0.09 µg/cm² for NM-51F) and sclera (28.01 ± 0.13 µg/cm²) compared to the control. This distribution pattern aligns with the structural differences between ocular tissues: the cornea's lipophilic epithelium favors retention of hydrophobic drugs like PSC, while the sclera’s collagen-rich matrix allows moderate hydrophilic uptake. Notably, NM-51F demonstrated superior tissue accumulation, likely due to optimal surfactant-drug interaction and controlled release kinetics. In vitro antifungal testing using disc diffusion assays showed that PSC-loaded micelles produced inhibition zones ranging from 34 to 35 mm against C. albicans ATCC 90028, exceeding the literature range (24–34 mm) for the standard PSC. Statistical analysis confirmed a significant difference (p = 0.KAT2B Antibody supplier 0093), suggesting that micellar encapsulation enhances antifungal potency—likely through improved aqueous solubility and increased effective drug concentration at the infection site.PMID:35145296
Safety evaluation via HET-CAM revealed minimal irritation. All formulations scored ≤1.5 on the cumulative toxicity scale, indicating “practically none” to “slight” irritation. Even the diluted Noxafil® suspension, known to be less suitable for ocular use, showed only slight toxicity. Importantly, the micellar systems hydrated with isotonic saline exhibited no adverse reactions beyond those seen with ultrapure water, confirming compatibility with ocular physiology.
In conclusion, TPGS-based micellar formulations represent a promising strategy for delivering posaconazole to the eye. They enhance ocular permeation and tissue penetration, maintain potent antifungal activity, and demonstrate favorable safety profiles. These findings support further development of micelle-mediated ocular delivery systems for managing refractory fungal eye infections.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
