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14 March 2018 Fluorescence lifetime imaging microscopy (FLIM) for visualization of targeted drug delivery and local distribution in skin of a single daily dose of topical minocycline gel: an update on translational research from preclinical to clinical (Conference Presentation)
Sinyoung Jeong, Maiko Hermsmeier, Sam Osseiran, Akira Yamamoto, Xin Chen, Usha Nagavarapu, Conor L. Evans, Kin F. Chan, AnnaMarie Daniels
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Proceedings Volume 10467, Photonics in Dermatology and Plastic Surgery 2018; 104670J (2018) https://doi.org/10.1117/12.2294084
Event: SPIE BiOS, 2018, San Francisco, California, United States
Abstract
Oral minocycline has been the standard of care for the treatment of non-nodular moderate to severe inflammatory acne vulgaris due to its inhibitory effects on the acne-causing Propionibacterium acnes bacterium and its anti-inflammatory properties, Despite the availability of an oral dosage form since 1966, a commercial topical minocycline remains elusive because of the challenges in stabilizing the active pharmaceutical ingredient (API) in a liquid/semisolid while ensuring sufficient uptake into targeted lesions. Recently, an investigative topical minocycline gel (BPX-01) has been developed to address the unmet needs for localized and targeted delivery while minimizing the risks of systemic side effects. Earlier preclinical studies pertaining to transepidermal delivery of the API had depended on semi-infinite doses of the 1%, 2% and 4% formulations to elicit enough fluorescence yield. We have subsequently shown evidence of minocycline delivery of 1% and 4% BPX-01 into the pilosebaceous unit of ex vivo human facial skin specimens dosed with about 2.5× daily dose using two-photon excitation fluorescence microscopy. In this study, we demonstrated another novel approach to identifying minocycline fluorescence signature using fluorescence lifetime imaging microscopy (FLIM) with phasor analysis. It was found that for a single daily dose and with FLIM, minocycline was consistently noted in the epidermis and hair follicle, with some incidence in the sebaceous gland for both 1% and 2% BPX-01. These observations corroborated with the recent success of a Phase 2b dose-finding study, with 2% BPX-01 meeting the primary endpoint of lesion reduction at week 12 with statistical significance over the vehicle.
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Sinyoung Jeong, Maiko Hermsmeier, Sam Osseiran, Akira Yamamoto, Xin Chen, Usha Nagavarapu, Conor L. Evans, Kin F. Chan, and AnnaMarie Daniels "Fluorescence lifetime imaging microscopy (FLIM) for visualization of targeted drug delivery and local distribution in skin of a single daily dose of topical minocycline gel: an update on translational research from preclinical to clinical (Conference Presentation)", Proc. SPIE 10467, Photonics in Dermatology and Plastic Surgery 2018, 104670J (14 March 2018); https://doi.org/10.1117/12.2294084
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KEYWORDS
Fluorescence lifetime imaging
Luminescence
Microscopy
Skin
Nonlinear optics
Pharmacology
Toxicology
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