A Systematic Safety Evaluation of Nanoporous Mannitol Material as a Dry-Powder Inhalation Carrier System

Zhang, Xuejuan; Xiao, Yumei; Cui, Yingtong; Zhao, Ziyu; Huang, Ying; Cai, Shihao; Wang, Guanlin; Wang, Wenhao; Pan, Xin; Wu, Chuanbin; Tan, Wen

doi:10.1016/j.xphs.2020.01.017

Cited by 9 publications

(5 citation statements)

References 75 publications

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“…The degradation products, namely, ferrocene and Ma, are benign and can be directly absorbed by the body. 55 Thus, these findings offer a new pathway for the utilization of COPs.…”

Section: ■ Results and Discussionmentioning

confidence: 87%

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Biodegradable Porous Polymeric Drug with pH-Stimuli-Responsive Delivery Capacity for Combined Cancer Therapy

Lou

Fang

Wang

et al. 2021

ACS Appl. Polym. Mater.

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Polymeric drugs are a class of drug in which the polymer itself acts as the active ingredient of the drug. Here, we constructed a biodegradable covalent organic porous polymer (COP), denoted as Fc-Ma, composed of clinical drug molecules, i.e., ferrocene (Fc) and D-mannitol (Ma) and pH-responsive acetal bonds. The coexistence of Fc and Ma brought special properties to Fc-Ma, which can be used directly as a polymeric drug integrating the performance of both components. Thus, this special COP features enzyme activity, which can catalyze the conversion of cellular H 2 O 2 to •OH through a Fenton-like reaction. As an artificial enzyme, Fc-Ma may overcome many of the limitations of natural enzymes with more pronounced catalytic activity in weakly acidic environments. Therefore, it enables the sufficient generation of reactive oxygen species (ROS) in tumors and effectively kills tumor cells. Meanwhile, the intrinsic open porous skeleton coupled with the large specific surface areas (393 m 2 g −1 ) makes Fc-Ma an ideal carrier for other drugs. For example, it presents a doxorubicin hydrochloride (DOX) drug loading capacity of 64.4 ± 0.27%, compared with individual drugs; the acetal linkage endowed Fc-Ma with passive targeting, resulting in highly controlled drug delivery with selective and sustained release in acidic media, almost twice as much as that under neutral conditions. Hence, the tumor microenvironment can not only stimulate the generation of multiple ROS but also induce the passive targeted release of DOX, thereby ensuring the accumulation of drugs in the cancer sites, preventing the nonspecific distribution of drugs in the whole body and protecting renal tissues against DOX-induced nephrotoxicity. In summary, Fc-Ma-DOX exhibits significant synergistic actions of enzymatic therapy and chemotherapy, thus significantly improving the overall therapeutic effect.

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“…The degradation products, namely, ferrocene and Ma, are benign and can be directly absorbed by the body. 55 Thus, these findings offer a new pathway for the utilization of COPs.…”

Section: ■ Results and Discussionmentioning

confidence: 87%

“…This could therefore solve the problem of carrier accumulation in the human body, effectively avoiding the side effects caused by the non-metabolized carrier. The degradation products, namely, ferrocene and Ma, are benign and can be directly absorbed by the body . Thus, these findings offer a new pathway for the utilization of COPs.…”

Section: Resultsmentioning

confidence: 90%

Biodegradable Porous Polymeric Drug with pH-Stimuli-Responsive Delivery Capacity for Combined Cancer Therapy

Lou

Fang

Wang

et al. 2021

ACS Appl. Polym. Mater.

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“…Induced by bacteria or viruses, lung infections are often debilitating and can sometimes be fatal. 47,60 Furthermore, the deep colonization nature of pathogen make it difficult for the traditional DDS to deliver drugs to infected lesions, resulting in unsatisfactory therapeutic outcomes. 61,62 Recently, the development of PDTNs shed light on the treatment of lung infection due to their versatility, showing great promise as a strategy for targeted therapy, and formulation strategies can be used to tune, modify, and control their payload release profile.…”

Section: Receptor-mediated Targeting Strategymentioning

confidence: 99%

Nanomedicines for targeted pulmonary delivery: receptor-mediated strategy and alternatives

Wang,

Zhong,

Huang

et al. 2024

Nanoscale

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“…These findings show the feasibility of pulmonary delivery of GLP-1RA and GLP-1 using particle engineering and the lungs can provide rapid absorption comparable to SC injection and high bioavailability (Qian, et al 2009;Sanketkumar and Amit December 2015). However, due to the lung safety concern, the use of excipients in DPI formulations should be minimised (Balducci, et al 2014;Zhang, et al 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Lactose is the most used carrier in DPI formulations (Nokhodchi and Martin 2015). However, lactose might not be the carrier of choice for peptides and proteins as it is a reducing sugar associated with chemical incompatibility (e.g., Maillard reaction) (Rahimpour, et al 2014;Zhang, et al 2020). In contrast, mannitol is non-reducing sugar and generally recognized as safe substance listed by the Food and Drug Administration (FDA) database (U.S.…”

Section: Introductionmentioning

confidence: 99%

Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations

Babenko

Alany

Calabrese

et al. 2022

International Journal of Pharmaceutics

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A Systematic Safety Evaluation of Nanoporous Mannitol Material as a Dry-Powder Inhalation Carrier System

Cited by 9 publications

References 75 publications

Biodegradable Porous Polymeric Drug with pH-Stimuli-Responsive Delivery Capacity for Combined Cancer Therapy

Biodegradable Porous Polymeric Drug with pH-Stimuli-Responsive Delivery Capacity for Combined Cancer Therapy

Nanomedicines for targeted pulmonary delivery: receptor-mediated strategy and alternatives

Development of drug alone and carrier-based GLP-1 dry powder inhaler formulations

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