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Safety evaluation of ultrasonic atomization inhalation of Zinc alginate hydrogel nanoparticles
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DOI   10.11656/j.issn.1672-1519.2019.09.19
Key Words   Zine alginate;hydrogel nanoparticle;ultrasonic atomization inhalation;safety
Author NameAffiliationE-mail
YUE Xiaoyue Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WU Jiarong Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
WANG Yanqiu Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China  
CUI Yuanlu Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China ylcui@tjutcm.edu.cn 
Abstract
    [Objective] A hydrogel nanoparticle preparation was developed as an ideal carrier for drug delivery,and the effects of nanoparticles via inhalation on the trachea and lung tissue were observed. The safety and feasibility of the inhalation drug delivery were preliminarily investigated.[Methods] The Zinc alginate hydrogel nanoparticles (ALG-NPs) were prepared by reverse microemulsion method,and characterized by determination of particle size and Zeta potential,transmission electron microscopy (TEM),differential scanning calorimetry (DSC) and fourier transform infrared spectroscopy (FT-IR). Forty-eight BALB/c mice were randomly divided into four groups,including the control,the ALG-NPs low,middle,and high dose (100,150,200 mg/kg) groups,and each group was also divided into 2 subgroups for 7 days and 14 days administration separately. Each group was administrated by inhaling ALG-NPs,once a day,20 min/time. After the last inhalation 1 h,the serum,lung tissue homogenate and pathology were determined.[Results] The average particle size of ALG-NPs was (71.24 ±2.12) nm,and the Zeta potential was (-19.4 ±0.64) mV. The results of characterization analysis indicated that the ALG-NPs system was successfully constructed. Compared with the control group,the lung tissue and trachea of the low and middle dose groups of ALG-NPs showed no abnormal lesions and the levels of inflammatory cytokines in serum and lung tissue homogenate were normal. Inflammatory cells infiltrated occasionally in the lung tissue,and IL-6 levels in serum and lung tissue homogenate were significantly increased in the ALG-NPs high dose group (14 days).[Conclusion] As a drug carrier,medium and low doses of ALG-NPs were safe,but long-term high dose of ALG-NPs inhalation had a certain irritating effect on the respiratory system,and the dose and inhalation time of ALG-NPs should be properly controlled.

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