期刊
ACS NANO
卷 12, 期 7, 页码 6851-6859出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b02099
关键词
supramolecular nanoparticles; controlled release; fluorescent probe; intradermal retention time; tattoo-mediated delivery
类别
资金
- National Institutes of Health [R21EB016270]
- Department of Radiology at USC
- National Natural Science Foundation of China [51603042, 51633001, 51721002]
- National Key R&D Program of China [2016YFC1100300]
- Ministry of Science and Technology, R.O.C.
- MOST [106-2113-M-002-013-MY2, 106-2113-M-005-001]
- Innovation and Development Center of Sustainable Agriculture from Featured Areas Research Center Program of the Higher Education Sprout Project by Ministry of Education (MOE) in Taiwan
- Institute of Nuclear Energy Research, Atomic Energy Council, Executive Yuan, R.O.C.
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.
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