journal article·2018-07-24

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

Fang Wang, Peng Yang, Jin-sil Choi, Petar Antovski, Yazhen Zhu, Xiaobin Xu, Ting-Hao Kuo, Li-En Lin, Diane N. H. Kim, Pin-Cheng Huang, Haoxiang Xu, Chin-Fa Lee, Changchun Wang, Cheng-Chih Hsu, Kai Chen, Paul S. Weiss, Hsian-Rong Tseng

ACS Nano· Volume 12· Issue 7
Publisher page

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.
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Research context

OpenAlex topics: Nail Diseases and Treatments · Laser Applications in Dentistry and Medicine · Ocular Surface and Contact Lens

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai 200433, China

Department of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging (CIMI), California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, California 90095-1770, United States

Department of Chemistry and Biochemistry, Department of Materials Science and Engineering, California NanoSystems Institute (CNSI), University of California, Los Angeles, Los Angeles, California 90095, United States

School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore

Department of Chemistry, National Taiwan University, Taipei 10617, Taiwan

Department of Bioengineering, University of California, Los Angeles, Los Angeles, California 90095, United States

Department of Chemistry, Research Center for Sustainable Energy and Nanotechnology, Innovation and Development Center of Sustainable Agriculture, National Chung Hsing University (NCHU), 145 Xingda Road, South Dist., Taichung 402, Taiwan

Department of Dermatology, Institute of Dermatology, Peking Union Medical College & Chinese Academy of Medical Sciences, 12 Jiangwangmiao Street, Xuanwu Dist., Nanjing 210042, China

Molecular Imaging Center, Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033-9061, United States

Funding

Institute of Nuclear Energy Research · Ministry of Science and Technology of the People's Republic of China · National Institute of Biomedical Imaging and Bioengineering · National Natural Science Foundation of China · Ministry of Science and Technology, Taiwan · Department of Radiology, University of Southern California

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