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 (KTZCc-FSMNPs) as an intradermal controlled release solution for treating onychomycosis. A two-step synthetic approach was adopted to prepare a variety of KTZCc-FSMNPs. Initial characterization revealed that 4800 nm KTZCc-FSMNPs exhibited high KTZ encapsulation efficiency/capacity, optimal fluorescent property, and sustained KTZ release profile. Subsequently, 4800 nm KTZCc-FSMNPs were chosen for in vivo studies using a mouse model, wherein the KTZCc-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 KTZCc-FSMNPs can serve as an effective treatment for onychomycosis.
[1]Fudan Univ, Dept Macromol Sci, State Key Lab Mol Engn Polymers, Shanghai 200433, Peoples R China;
[2]Univ Calif Los Angeles, Calif NanoSyst Inst CNSI, CIMI, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA;
[3]Univ Calif Los Angeles, Calif NanoSyst Inst CNSI, Dept Mat Sci & Engn, Dept Chem & Biochem, Los Angeles, CA 90095 USA;
[4]Nanyang Technol Univ, Sch Mat Sci & Engn, 50 Nanyang Ave, Singapore 639798, Singapore;
[5]Univ Southern Calif, Keck Sch Med, Dept Radiol, Mol Imaging Ctr, Los Angeles, CA 90033 USA;
[6]Natl Taiwan Univ, Dept Chem, Taipei 10617, Taiwan;
[7]Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA;
[8]NCHU, Innovat & Dev Ctr Sustainable Agr, Res Ctr Sustainable Energy & Nanotechnol, Dept Chem, 145 Xingda Rd, Taichung 402, Taiwan;
[9]Peking Union Med Coll, Inst Dermatol, Dept Dermatol, 12 Jiangwangmiao St, Nanjing 210042, Jiangsu, Peoples R China;
[10]Chinese Acad Med Sci, 12 Jiangwangmiao St, Nanjing 210042, Jiangsu, Peoples R China
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