Cross-Linked Fluorescent Supramolecular Nanoparticles for Intradermal Controlled Release of Antifungal Drug—A Therapeutic Approach for Onychomycosis

Abstract

The existing approaches to onychomycosis demonstrate limited success since the commonly used oral administration and topical cream only achieve temporary effective drug concentration at the fungal infection sites. An ideal therapeutic approach for onychomycosis should have (i) the ability to introduce antifungal drugs directly to the infected sites; (ii) finite intradermal sustainable release to maintain effective drug levels over prolonged time; (iii) a reporter system for monitoring maintenance of drug level; and (iv) minimum level of inflammatory responses at or around the fungal infection sites. To meet these expectations, we introduced ketoconazole-encapsulated cross-linked fluorescent supramolecular nanoparticles (KTZ⊂c-FSMNPs) as an intradermal controlled release solution for treating onychomycosis. A two-step synthetic approach was adopted to prepare a variety of KTZ⊂c-FSMNPs. Initial characterization revealed that 4800 nm KTZ⊂c-FSMNPs exhibited high KTZ encapsulation efficiency/capacity, optimal fluorescent property, and sustained KTZ release profile. Subsequently, 4800 nm KTZ⊂c-FSMNPs were chosen for in vivo studies using a mouse model, wherein the KTZ⊂c-FSMNPs were deposited intradermally via tattoo. The results obtained from (i) in vivo fluorescence imaging, (ii) high-performance liquid chromatography quantification of residual KTZ, (iii) matrix-assisted laser desorption/ionization mass spectrometry imaging mapping of KTZ distribution in intradermal regions around the tattoo site, and (iv) histology for assessment of local inflammatory responses and biocompatibility, suggest that 4800 nm KTZ⊂c-FSMNPs can serve as an effective treatment for onychomycosis.

Novel Drug Delivery Strategies for the Treatment of Onychomycosis

“…In vivo studies using tattoo were carried out on a mouse model. The results support the use of ketoconazole-encapsulated crosslinked fluorescent supramolecular nanoparticles as an intradermal controlled release solution for treating onychomycosis [56].…”

Nanopartículas de plata en el tratamiento de la micosis asociada al pie diabético

“…Otros nanoproductos han demostrado capacidad antifúngica contra T. rubrum (35) . Un estudio reciente exploró el uso de nanopartículas como vehículo para ketoconazol en forma intradérmica controlada y sostenida en micosis superficial (36) .…”

Host-Guest Chemistry in Supramolecular Theranostics

“…Tseng et al . fabricated KTZ-encapsulated cross-linked fluorescent supramolecular nanoparticles (KTZ/c-FSMNPs) to increase therapeutic results by controlling the in vivo release behavior of KTZ 134. Ad-PEG, Ad-PAMAM, and CD-PEI were used as the molecular building blocks to construct supramolecular nanoparticles through a multivalent molecular recognition between Ada and β -CD.…”