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Polymeric Gene Delivery Carriers for Pulmonary Diseases
Published in Severian Dumitriu, Valentin Popa, Polymeric Biomaterials, 2020
Xiang Gao, Regis R. Vollmer, Song Li
Most of cationic homopolyamino acids are not very effective transfection agents in vitro and in vivo due to poor endosome escape and slow complex dissociation. A high MW poly(oligod-arginine) was synthesized by polymerizing cys-nonargine-cys peptide units through terminal cysteine residues to form oligomers with reducible disulfide bonds. The high MW poly(oligo-darginine) is expected to break down to promote the dissolution of the polyplexes intracellularly once they are exposed to reducing environment in cytosol. In vivo transfection in lungs by intratracheal instillation of DNA/poly(oligo-d-arginine) polyplexes resulted in higher levels of gene expression than PEI polyplexes, which lasted for 1 week without toxicity. These data suggest poly(oligo-d-arginine) could be a promising nonviral gene carrier for lung diseases (Won et al., 2010).
Biological Activity
Published in Grimmer Gemot, Dr. Chem., Environmental Carcinogens: Polycyclic Aromatic Hydrocarbons, 1983
Intratracheal instillation is a relatively simple technique, and therefore is frequently used in the testing of chemicals which are potentially carcinogenic to the respiratory tract. As with implantation, instillation has the advantage of permitting exact determination of the administered dose per animal. On the other hand the distribution of substances in the pulmonary region is more homogenous in comparison with implantation. Instillation permits the application of relatively high doses in comparatively short time periods while the contamination of the skin is reduced to a minimum. It is even possible to apply a substance into one lobe of the lung only. Furthermore, the effect of particles and substances which are normally inhaled can be investigated, thus avoiding the inevitable nasal breathing of rodents. Consequently, the size and shape of particles are of minor importance in this type of application. When assessing the carcinogenic response, it seems to be important to examine whether the effect of a substance is increased or decreased by other less or noncarcinogenic substances. It is also necessary to investigate whether substances which are not carcinogenic as such can produce a carcinogenic effect after concurrent application with unspecific substances. Here the simultaneous application of carriers is of particular importance.
The State of the Science: Human Health, Toxicology, and Nanotechnology Risks
Published in Jo Anne Shatkin, Nanotechnology, 2017
Li and colleagues (2007) reported that the lung responses to inhalation of SWCNTs include inflammation changes. Subjects exposed to inhalation of MWCNTs showed moderate proliferation and thickening of alveolar walls. In some cases, intratracheal instillation appeared to cause more severe effects than via inhalation exposure. The study by Li et al. reported that after two weeks of inhalation exposure, MWCNTs were engulfed by alveolar macrophages and the MWCNTs were distributed throughout the lung. No increases in inflammatory cell infiltration were found, with a lack of inflammation, granuloma formation, fibrosis, and tissue injury.
PM2.5 aggravates airway inflammation in asthmatic mice: activating NF-κB via MyD88 signaling pathway
Published in International Journal of Environmental Health Research, 2023
Lei Wang, Yanzhi Cui, Hu Liu, Jing Wu, Jie Li, Xiansheng Liu
All mice were anesthetized with isoflurane, and grade VII OVA (Sigma Aldrich, St. Louis, MO) and PM2.5 solution were administered by intratracheal instillation alone or in combination into the trachea for five times at D0-D4 in the sensitization stage and four times at D10-D13 in the excitation stage. Airway hyper-responsiveness test was conducted and bronchoalveolar lavage fluid, serum and lung tissues were collected at the 14th day. The left lung tissue was used for RNA and protein extraction, and the right lung tissue was used for hematoxylin and eosin (HE) and periodic acid-schiff (PAS) staining analysis. We customised a complete set of instruments to ensure the accuracy of administration site and dose and to minimise interference factors, and the procedures were completed by an experienced laboratory personnel to minimise harm into the animal. The mice died during the experiment.
Nanomaterial-induced toxicity in pathophysiological models representative of individuals with pre-existing medical conditions
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Sreejesh Sreedharan, Georgios Zouganelis, Samantha J Drake, Gyanendra Tripathi, Ali Kermanizadeh
Han et al. (2011) studied the toxicity of SiO2 NMs in allergic asthma rodent models. In this investigation, ovalbumin (OVA)-treated (to induce pulmonary inflammation) and saline control 8-week-old Wistar rats were exposed to approximately 20 nm NMs for 30 days at daily doses of 4 or 8 µg via intratracheal instillation. Data demonstrated that the high dose NM exposure resulted in airway remodeling and aggravated inflammation which was significantly worse in the OVA-treated animals. Further, the IL4 levels in lung homogenates of NM-exposed animals was significantly higher in OVA exposed compared to controls. Han et al. (2011) concluded that the SiO2 NMs were involved in the development and exacerbation of non-eosinophilic inflammation due to the Th1/Th2 cytokine imbalance as evidenced by increased labels of IL4.
Jujuboside B post-treatment attenuates PM2.5-induced lung injury in mice
Published in International Journal of Environmental Health Research, 2022
Soo Ho Ryu, Nayeon Kim, Chaeyeong Kim, Jong-Sup Bae
In vivo administration of PM2.5 (10 mg/kg) in mice induced lung damage and inflammation. Previous studies reported that intraperitoneal instillation of PM2.5 (10 mg/kg) induced systemic and local acute inflammation and/or stimulated functional and histological changes in mouse lung tissue resulting in respiratory and cardiovascular dysfunction (Zhang et al. 2016a; Xu et al. 2018a; Choi et al. 2019). Intranasal inhalation and intratracheal instillation are the main methods of PM2.5 exposure in animal models. Intratracheal instillation is often performed in mice and hamsters by insertion of needles into the mouth and throat. In this study, PM2.5 was injected by intratracheal instillation. Previous studies have reported that intratracheal administration of PM2.5 causes lung damage by induction of inflammatory responses, alveolar epithelial dysfunction, and increasing pulmonary vessel permeability (Yan et al. 2017; Wang et al. 2018b). Intratracheal administration has a number of disadvantages, including non-physiological and invasive properties, alteration of the effect of anesthesia, and the means of delivery, as well as bypassing the upper respiratory tract (Morimoto et al. 2016). Despite these disadvantages, it is an effective and convenient method to induce lung damage in mice since only a single injection is required (Cho et al. 2018).