Lung-Targeted Delivery of Cepharanthine by an Erythrocyte-Anchoring Strategy for the Treatment of Acute Lung Injury

Zheng, Jinpeng; Lu, Caihong; Yang, Meiyan; Sun, Jiejie; Zhang, Jinbang; Meng, Yuanyuan; Wang, Yuli; Li, Zhiping; Yang, Yang; Gong, Wenbin; Gao, Chunsheng

doi:10.3390/pharmaceutics14091820

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…Other researchers have also used an erythrocyte anchoring strategy where they encapsulated CEP in chitosan-coated nanoparticles and bound them to erythrocytes in a non-covalent manner. This strategy has demonstrated efficacy in mouse models of ALI, where the nanoparticles were successfully targeted to the pulmonary system, mitigating the inflammatory damage within the lungs [41]. However, most of the current studies on the treatment of ALI with CEP have been in the form of injectable administration, including intraperitoneal and intravenous injections [41,42].…”

Section: Discussionmentioning

confidence: 99%

“…This strategy has demonstrated efficacy in mouse models of ALI, where the nanoparticles were successfully targeted to the pulmonary system, mitigating the inflammatory damage within the lungs [41]. However, most of the current studies on the treatment of ALI with CEP have been in the form of injectable administration, including intraperitoneal and intravenous injections [41,42]. However, CEP has poor oral absorption and low bioavailability due to its hydrophobic nature.…”

Section: Discussionmentioning

confidence: 99%

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Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Liang¹,

Wang²,

Chen³

et al. 2023

Molecules

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Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Liang¹,

Wang²,

Chen³

et al. 2023

Molecules

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“…Intravenously injected nanoparticles have difficulty crossing the alveolar/capillary barrier due to strong shear stress between RBCs and capillaries, and therefore be removed from RBCs membrane surfaces in lung. 48 Desorbed nanoparticles mainly accumulated in lung endothelial cells which realizing drug delivery targeting lung; meanwhile avoiding clearance of nanoparticles by liver and spleen. 30,49 Such RBC-hitchhiking strategy plays important therapeutic effect in treatment of lung metastatic tumors.…”

Section: Rbcs-hitchhikingmentioning

confidence: 99%

“…RBC‐hitchhiking can significantly enhance DDS targeting lung tumors by non‐covalent adsorption. Intravenously injected nanoparticles have difficulty crossing the alveolar/capillary barrier due to strong shear stress between RBCs and capillaries, and therefore be removed from RBCs membrane surfaces in lung 48 . Desorbed nanoparticles mainly accumulated in lung endothelial cells which realizing drug delivery targeting lung; meanwhile avoiding clearance of nanoparticles by liver and spleen 30,49 .…”

Section: Application Of Erythrocytes As Nanocarriers In Tumor Therapymentioning

confidence: 99%

Red blood cell derived nanocarrier drug delivery system: A promising strategy for tumor therapy

Wang,

Mao,

Zhang

et al. 2024

Interdisciplinary Medicine

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Nano drug delivery systems have been widely used in tumor therapy. Researchers have been devoted to exploring novel nano‐carriers to prolong circulation time biocompatibility and tumor targeting efficiency in vivo. Erythrocyte membranes as bionic nano‐drug delivery systems have attracted more attention recently. There are abundant red blood cells (RBCs) in circulation, which are natural carriers for nanomaterial delivery. There are mainly two strategies to use RBCs as nanomaterial carriers: RBC‐hitchhiking and bionic nanomaterial coated with erythrocyte membrane loading with drugs. Although nano‐carrier based on RBCs have yielded some progress, the mechanism of mutual effect between nanoparticles and RBCs is still unclear. Here, we review the effects of nanoparticles on RBCs (morphology and function, etc) and application of RBCs membrane as nano‐drug delivery carriers in tumor therapy.

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“…The clinical application of cepharanthine is limited due to its poor water solubility and low oral bioavailability [ 262 ]. At present, the commercial dosage forms of cepharanthine are mainly ordinary tablets.…”

Section: Conclusion and Prospectivesmentioning

confidence: 99%

Pharmacological Activity of Cepharanthine

et al. 2023

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Cepharanthine, a natural bisbenzylisoquinoline (BBIQ) alkaloid isolated from the plant Stephania Cephalantha Hayata, is the only bisbenzylisoquinoline alkaloid approved for human use and has been used in the clinic for more than 70 years. Cepharanthine has a variety of medicinal properties, including signaling pathway inhibitory activities, immunomodulatory activities, and antiviral activities. Recently, cepharanthine has been confirmed to greatly inhibit SARS-CoV-2 infection. Therefore, we aimed to describe the pharmacological properties and mechanisms of cepharanthine, mainly including antitumor, anti-inflammatory, anti-pathogen activities, inhibition of bone resorption, treatment of alopecia, treatment of snake bite, and other activities. At the same time, we analyzed and summarized the potential antiviral mechanism of cepharanthine and concluded that one of the most important anti-viral mechanisms of cepharanthine may be the stability of plasma membrane fluidity. Additionally, we explained its safety and bioavailability, which provides evidence for cepharanthine as a potential drug for the treatment of a variety of diseases. Finally, we further discuss the potential new clinical applications of cepharanthine and provide direction for its future development.

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Lung-Targeted Delivery of Cepharanthine by an Erythrocyte-Anchoring Strategy for the Treatment of Acute Lung Injury

Cited by 6 publications

References 41 publications

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury

Red blood cell derived nanocarrier drug delivery system: A promising strategy for tumor therapy

Pharmacological Activity of Cepharanthine

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