Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Zhang, Xuejuan; Cui, Yingtong; Liang, Ruifeng; Wang, Guanlin; Xiao, Yumei; Zhao, Ziyu; Huang, Zhengwei; Huang, Ying; Geng, Jianfang; Pan, Xin; Wu, Chuanbin

doi:10.1016/j.apsb.2020.02.013

Cited by 14 publications

(8 citation statements)

References 68 publications

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“…After being nebulized, the sprayed nanoreactor suspension would form liquid droplets with an aerodynamic particle size of about 4.8 μm. With a series of delivery processes including impaction, sedimentation, and interception, the liquid droplet would deposit in the respiratory tract . Then, the nanoreactor would cross through the epithelial layer to reach lung ADC lesions.…”

Section: Resultsmentioning

confidence: 99%

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

Wang

Huang

et al. 2022

ACS Nano

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Ferroptosis therapy by catalyzing the Fenton reaction has emerged as a promising tumor elimination strategy for lung adenocarcinoma (ADC). However, the unsatisfactory Fenton reaction efficiency, strong intracellular antioxidant system, and insufficient lung drug accumulation limits the ferroptosis therapeutic effect. To address these issues, an inhalable nanoreactor was proposed by spontaneously adsorbing biomimetic protein corona (PC) composed of matrix metalloproteinase 2 responsive gelatin and glutamate (Glu) on the surface of cationic nanostructured lipid carriers (NLC) core loaded with ferrocene (Fc) and fluvastatin. The prepared Fc-NLC(F)@PC could be nebulized into lung lesions with 2.6 times higher drug accumulation and boost lipid peroxide production by 3.2 times to enhance ferroptosis therapy. Mechanically, fluvastatin was proved to inhibit monocarboxylic acid transporter 4 mediated lactate efflux, inducing tumor acidosis to boost Fc-catalyzing reactive oxygen species production, while the extracellular elevating Glu concentration was found to inhibit xCT (system Xc –) functions and further collapse the tumor antioxidant system by glutathione synthesis suppression. Mitochondrial dysfunction and cell membrane damage were involved in the nanoreactor-driven ferroptotic cell death process. The enhanced antitumor effects by combination of tumor acidosis and antioxidant system collapse were confirmed in an orthotopic lung ADC tumor model. Overall, the proposed nanoreactor highlights the pulmonary delivery approach for local lung ADC treatment and underscores the great potential of ferroptosis therapy.

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Section: Resultsmentioning

confidence: 99%

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

Wang

Huang

et al. 2022

ACS Nano

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“…The powders of RES- β -CD were suitable as a kind of DPIs. DPIs possess excellent properties, such as high drug loads, portability, propellant-free, and good stability (Zhang et al., 2020 ). However, the development of DPI formulations is a challenge for many drugs because of their high-dose needs and improper physicochemical properties.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary delivery of resveratrol-β-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury

Wang

Liu²,

Pan

et al. 2022

Drug Delivery

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Smoke bombs are often used in military/fire training, which can produce a large amount of zinc chloride (ZnCl 2 ) smoke. Inhalation of ZnCl 2 smoke usually causes acute lung injury (ALI) that would likely develop to acute respiratory distress syndrome (ARDS). However, there is no effective prevention or treatment strategy for the smoke-induced ALI. Resveratrol (RES) is a natural polyphenol with good anti-inflammatory and anti-apoptotic activities, but its low solubility, stability, and bioavailability restrict its clinical application. In this study, an inhalable RES formulation composed of RES- β -cyclodextrin inclusion complexes (RES- β -CD) was prepared for the prevention of ZnCl 2 smoke-induced ALI. RES- β -CD powders had a small mass median aerodynamic diameter of 3.61 μm and a high fine particle fraction of 38.84%, suitable for pulmonary inhalation. RES- β -CD exhibited low BEAS-2B cytotoxicity. Pulmonary delivery of RES- β -CD to mice remarkably prevented the smoke-induced ALI with downregulation of TNF- α , IL-1 β , STAT3, and GATA3, and upregulation of T-bet and Foxp3. RES- β -CD protected the respiratory function, percutaneous oxygen saturation, physical activity, lung capillary integrity, and lung liquid balance, alleviating inflammation and apoptosis. Pulmonary delivery of the positive drug, budesonide (BUD), also alleviated the smoke-induced ALI by reduction of inflammation and cell apoptosis. RES- β -CD exhibited the regulation of the Th1/Th2 and Treg/Th17 balances, while BUD did not show any effect on immune balances. In conclusion, pulmonary delivery of RES- β -CD is a promising anti-inflammatory and anti-apoptosis strategy for the prevention of ZnCl 2 smoke-induced ALI by direct lung drug distribution and regulation of immune balance.

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“…A batch of 20 capsules of each model DPIs were shot in each run under air flow rate of 60 L/min for 4 s. Ultra-pure water was used to collect MSS and LAC deposition on the inhaler device, adaptor, induction port, pre-separator, all NGI stages and micro orifice collector (MOC). The deposition profile of MSS and LAC was obtained by high performance liquid chromatography (HPLC) quantification 15 . The experiments were conducted in triplicates.…”

Section: Methodsmentioning

confidence: 99%

“…The modular process analysis platform (MPAP), developed in our previous research, demonstrated a potential to reach this goal. Previously, MPAP was applied to explore the influence of air flow rate during the PDPs 15 . The detailed mechanisms of air flow rate for PDPs of DPIs were successfully demonstrated, whose reliability was also preliminarily verified by NGI.…”

Section: Introductionmentioning

confidence: 99%

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

Cui

Huang

Zhang

et al. 2022

Acta Pharmaceutica Sinica B

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Dry powder inhalers (DPIs) had been widely used in lung diseases on account of direct pulmonary delivery, good drug stability and satisfactory patient compliance. However, an indistinct understanding of pulmonary delivery processes (PDPs) hindered the development of DPIs. Most current evaluation methods explored the PDPs with over-simplified models, leading to uncompleted investigations of the whole or partial PDPs. In the present research, an innovative modular process analysis platform (MPAP) was applied to investigate the detailed mechanisms of each PDP of DPIs with different carrier particle sizes (CPS). The MPAP was composed of a laser particle size analyzer, an inhaler device, an artificial throat and a pre-separator, to investigate the fluidization and dispersion, transportation, detachment and deposition process of DPIs. The release profiles of drug, drug aggregation and carrier were monitored in real-time. The influence of CPS on PDPs and corresponding mechanisms were explored. The powder properties of the carriers were investigated by the optical profiler and Freeman Technology four powder rheometer. The next generation impactor was employed to explore the aerosolization performance of DPIs. The novel MPAP was successfully applied in exploring the comprehensive mechanism of PDPs, which had enormous potential to be used to investigate and develop DPIs.

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Novel approach for real-time monitoring of carrier-based DPIs delivery process via pulmonary route based on modular modified Sympatec HELOS

Cited by 14 publications

References 68 publications

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

Pulmonary delivery of resveratrol-β-cyclodextrin inclusion complexes for the prevention of zinc chloride smoke-induced acute lung injury

A real-time and modular approach for quick detection and mechanism exploration of DPIs with different carrier particle sizes

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