Development of Aggregation-Caused Quenching Probe-Loaded Pressurized Metered-Dose Inhalers with Fluorescence Tracking Po
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Research Article Development of Aggregation-Caused Quenching Probe-Loaded Pressurized Metered-Dose Inhalers with Fluorescence Tracking Potentials Wenhua Wang,1 Zhengwei Huang,1,2 Ke Xue,1 Jiaye Li,1 Wenhao Wang,1 Jingyi Ma,3 Cheng Ma,1 Xuequn Bai,1 Ying Huang,2,4 Xin Pan,1,4 and Chuanbin Wu1,2
Received 8 July 2020; accepted 11 August 2020 Abstract. Recently, pressurized metered-dose inhalers (pMDIs) are getting more attention as an effective approach of pulmonary drug delivery, and nanoparticle-based formulations have become a new generation of pMDIs, especially for water insoluble drugs. Up until now, there is no clinical application of nanoparticle-based pMDIs. The main hurdle remains in the lack of knowledge of the in vivo fate of those systems. In this study, a fluorescent probe named P4 with aggregation-caused quenching (ACQ) effect was loaded in the nanoparticle-based pMDIs to track the in vivo fate. P4 probe expressed strong fluorescence when distributed in intact nanoparticles, but quenched in the in vivo aqueous environment due to molecular aggregation. Experimentally, P4 probe was encapsulated into solid lipid nanoparticles (SLN) as P4-SLN, and then, the formulation of pMDIs was optimized. The content (w/w) of the optimal formulation (P4-SLN-pMDIs) was as follows: 6.02% Pluronic® L64, 12.03% ethanol, 0.46% P4-SLN, and 81.49% 1,1,1,2-tetrafluoroethane (HFA-134a). P4-SLN-pMDI was transparent in appearance, possessed a particle size of 132.07 ± 3.56 nm, and the fine particle fraction (FPF) was 39.53 ± 1.94%, as well good stability was shown within 10 days. The results indicated P4-SLN-pMDI was successfully prepared. Moreover, the ACQ property of P4-SLN-pMDIs was verified, which ensured the fluorescence property as a credible tool for in vivo fate study. Taken together, this work established a platform that could provide a firm theoretical support for exploration of the in vivo fate of nanoparticle-based pMDIs in subsequent studies. KEY WORDS: aggregation-caused quenching; pressurized metered-dose inhalers; solid lipid nanoparticles.
INTRODUCTION Pulmonary diseases are among the leading causes of morbidity and mortality worldwide, which remain a major health issue across the globe (1,2). For instance, chronic obstructive pulmonary disease (COPD) kills more than 3 million people worldwide every year (3–5). Continuous Wenhua Wang and Zhengwei Huang contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1208/s12249-020-01782-1) contains supplementary material, which is available to authorized users. 1
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, Guangdong, People’s Republic of China. 2 College of Pharmacy, Jinan University, Guangzhou, 511443, Guangdong, People’s Republic of China. 3 Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE68198, USA. 4 To whom correspondence should be addressed. (e–mail: [email protected]; [email protected])
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