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Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.
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Anemoside B4 (B4), a main triterpenoid saponin from a traditional Chinese medicine plant, Pulsatilla chinensis, is a novel anti-inflammatory agent for protection from acute lung injury. We investigated the pulmonary availability and anti-inflammatory efficacy of B4 after intratracheal and intravenous dosing with a view to evaluating the suitability of inhalation delivery. All animal studies were performed under the guidelines approved by the Animal Care and Use Committee of Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences (Approval No: SLXD-20181113046). In vitro evaluation of the aerodynamic characteristics and droplet size distribution showed that the aerosols generated by a commercially available nebulizer were well deposited in the respiratory tract. Following intratracheal administration, B4 underwent pulmonary absorption into the bloodstream, rendering an absolute bioavailability of 103%. Compared to intravenous delivery, intratracheal administration dramatically increased the drug availability in lung tissue of rats by more than 1 000-fold, leading to improved and prolonged concentrations of B4 in lung tissue up to 48 h. In addition, the intratracheal administration of B4 resulted in dose-dependent and prolonged anti-inflammatory efficacy in a lipopolysaccharide (LPS)-induced lung injury model in mice. The present results demonstrate that inhalation delivery of B4 is a promising approach to treat pulmonary inflammation with once-daily dosing.
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The heparin polysaccharide nanoparticles block the interaction between heparan sulfate/S protein and inhibit the infection of both wild-type SARS-CoV-2 pseudovirus and the mutated strains through pulmonary delivery.Image 1.
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Objective:To review the drug absorption evaluation methods for pulmonary delivery. Methods: The drug absorption cell models, in vitro pulmonary membrane model and in vivo animal model were systematically summarized, and the advantages and disadvantages of those models and applications were reviewed by referring to the databases in CNKI and Pubmed. Results:The appro-priate animal model and method for the study of pulmonary absorption should be chosen according to the experimental purpose and char-acteristics of drugs. Conclusion:The review provides the thoughts and theoretical basis for the research and development of pulmonary delivery.
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Objective To study the rat pulmonary irritant of aerosol inhaled Tanreqing and Reduning injection .Methods Rats were devided into two groups for each medicine (low concentration group and high concentration group ) ,nebulized drug administration for seven days ,with the control group irrigated with saline ,and were sacrificed .Through bronchoalveolar lav-age ,excurrent bronchoalveolar lavage fluid (BALF) was used for total protein determination and LDH vitality test to evaluate pulmonary toxicity of two medicines .Results The protein concentrations of two groups in low and high concentrations of Tan-reqing and Reduning respectively are (193 .78 ± 27 .74) ,(235.33 ± 50.41)μg/ml;(174 .02 ± 17 .82) ,(227 .27 ± 66 .03)μg/ml;LDH vitalities respectively are 1065 .21 ± 181 .76 ,1467 .33 ± 101 .87;307 .97 ± 47 .56 ,1377 .29 ± 566 .48 .By t-test ,compared with normal saline ,there was no significant effect among these five groups on protein concentration ,but these two medicine were able to improve LDH activity (P<0 .05) which was more obvious in high concentration group .When two medicines were in low concentration ,LDH activity was higher in Tanreqing group with statistical significance (P<0 .05) .Conclusion Aero-sol inhaled Tanreqing and Reduning injection in rats have some pulmonary irritation and potential safety hazard in this delivery w ay .
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OBJECTIVE: To summary the common methods that used to assay dry powder inhaler in vivo, and provide a theoretical basis and some research ideas for relative research.
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Aim: To prepare the influenza vaccine lyophilized liposomes and to characterize its particle distribution, encapsulation efficiency and immunogenicity. Methods: Flu vaccine liposome based on the method of thin-film evaporation was prepared using phospholipids , cholesterol and the purified influenza virus split vaccine, and was further subjected to frozen-drying. The polymorph was observed by microscope; the particle distribution and the average size were analysed by transmission electron microscope; its encapsulation efficiency was determined by Lowry method and the antibody titers were assessed by hemagglutination-inhibition after pulmonary delivery to mice. Results: The reconstitated influenza vaccine liposome under electronic microscope were round or elliptic particles evenly distributed at a mean size of 2. 14 祄, with the encapsulation efficiency of more than 80%. The antibody titer through pulmonary delivery was higher than that through intraperitoneal injection. Conclusion: The prepared influenza vaccine lyophilized liposomes possess high encapsulation efficiency, better particle distribution and marked immunogenicity through pulmonary delivery to mice. Pulmonary delivery of influenza vaccine liposomes is a potential immunization approach worthy of further exploitation.