Abstract:Bronchiolitis Obliterans Syndrome seriously reduces long-term survival of lung transplanted patients. Up to now there is no effective therapy once BOS is established. Nanomedicine introduces the possibility to administer drugs locally into lungs increasing drug accumulation in alveola reducing side effects. Imatinib was loaded in gold nanoparticles (GNP) functionalized with antibody against CD44 (GNP-HCIm). Lung fibroblasts (LFs) were derived from bronchoalveolar lavage of BOS patients. GNP-HCIm cytotoxicity w… Show more
“…15 ). Pandolfi et al [ 86 ] have reported inhalable imatinib loading gold nanoparticles, which functionalized with antibody against CD44, demonstrating significant reduction tracheal lumen obliteration and apoptosis, and TGF-β-positive signal in surroundings. Fig.…”
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
“…15 ). Pandolfi et al [ 86 ] have reported inhalable imatinib loading gold nanoparticles, which functionalized with antibody against CD44, demonstrating significant reduction tracheal lumen obliteration and apoptosis, and TGF-β-positive signal in surroundings. Fig.…”
It is reported that pulmonary fibrosis has become one of the major long-term complications of COVID-19, even in asymptomatic individuals. Currently, despite the best efforts of the global medical community, there are no treatments for COVID-induced pulmonary fibrosis. Recently, inhalable nanocarriers have received more attention due to their ability to improve the solubility of insoluble drugs, penetrate biological barriers of the lungs and target fibrotic tissues in the lungs. The inhalation route has many advantages as a non-invasive method of administration and the local delivery of anti-fibrosis agents to fibrotic tissues like direct to the lesion from the respiratory system, high delivery efficiency, low systemic toxicity, low therapeutic dose and more stable dosage forms. In addition, the lung has low biometabolic enzyme activity and no hepatic first-pass effect, so the drug is rapidly absorbed after pulmonary administration, which can significantly improve the bioavailability of the drug. This paper summary the pathogenesis and current treatment of pulmonary fibrosis and reviews various inhalable systems for drug delivery in the treatment of pulmonary fibrosis, including lipid-based nanocarriers, nanovesicles, polymeric nanocarriers, protein nanocarriers, nanosuspensions, nanoparticles, gold nanoparticles and hydrogel, which provides a theoretical basis for finding new strategies for the treatment of pulmonary fibrosis and clinical rational drug use.
“…Imatinib (100-400 mg daily) seemed to stabilise FEV 1 in some BOS patients after allogeneic haematopoietic stem cell transplantation, and in subgroup analyses of some patients treated with imatinib for chronic GvHD. (Magro et al, 2009;Olivieri et al, 2013;Olivieri et al, 2009;Parra Salinas et al, 2021;Stadler et al, 2009;Sánchez-Ortega et al, 2016;Watanabe et al, 2015) There is minimal data from preclinical animal studies regarding the use of imatinib in CLAD, showing that imatinib improved luminal airway obstruction in experimental bronchiolitis obliterans (Pandolfi et al, 2020;von Suesskind-Schwendi et al, 2013;Watanabe et al, 2017), possibly through reduction of migration and differentiation of fibrocytes in the allograft (Watanabe et al, 2017).…”
Take Home Message (225 char): Effective treatments to prevent the onset and progression of CLAD are still a major shortcoming. Based on existing data to date, considering both efficacy and risk of side effects, ECP, ATG and TLI are currently the most viable second-line treatment options for CLAD.
Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second‐line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non‐small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS‐PEG‐Ab‐Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS‐PEG‐Ab‐Im was 25–30 nm, its surface charge was 13.1 mV, and the shape of CS‐PEG‐Ab‐Im was nearly spherical and cylindrical. The therapeutic potential of CS‐PEG‐Ab‐Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS‐PEG‐Ab‐Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS‐PEG‐Ab‐Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS‐PEG‐Ab. Besides, cell arresting result exhibits the CS‐PEG‐Ab‐Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS‐PEG‐Ab‐Im can be an ideal nanosystem in NSCLC treatment.
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