![]() ![]() Pulmonary drug delivery presents various advantages over oral and parenteral routes for localized treatment of chronic lung disorders. Therefore, the use of an effective carrier may help to improve these unfavorable physiochemical and pharmacokinetic properties and possibly enhance its treatment potential while reducing off-target cytotoxicity. Despite encouraging in vitro and preclinical efficacy, the clinical applications of Cela remain challenging due to its extremely low aqueous solubility, low bioavailability, narrow therapeutic window, and potential toxicity. Cela has also been reported to induce autophagy and cause tumor growth inhibition. Additionally, Cela has been shown to induce apoptosis in cancer cells by activating apoptotic proteins such as caspase-3/8/9. Numerous studies have demonstrated Cela’s intriguing pharmacological properties, including anti-inflammation, neuroprotection, and anti-cancer. ![]() Since MPM has been studied less extensively than other primary neoplasms of the chest, there is an increased urgency to explore and develop more efficacious treatment options while minimizing side effects.Ĭelastrol (Cela) is an extensively studied phytochemical derived from the root extract of Tripterygium wilfordii Hook F (Thunder God Vine), which has demonstrated interesting and promising bioactivity. Current therapies include surgical resection or combinations of chemotherapy, radiation, and immunotherapy however, these approaches have not shown great success with patients experiencing multiple adverse side effects and only give a ~10% 5-year survival rate. Additionally, roughly 3000 new cases are diagnosed each year in the United States. Due to a latency period in tumor development of 20–50 years after exposure to asbestos, the incidences of MPM have increased slightly in the last decade, especially in industrialized countries, such as the UK, Australia, and Belgium. Occupational exposure to asbestos fibers has been identified as the major cause of MPM in patients, leading to various symptoms, such as difficulty breathing, chest pain, fluid buildup, and others. MM is classified as a rare disease with ~30,000 new cases diagnosed worldwide annually, with a subtype, malignant pleural mesothelioma (MPM), accounting for 80–90% of all MM cases. Malignant mesothelioma (MM) is a rare, incurable, and malignant type of cancer arising from the mesothelial or sub-mesothelial cells of the pleura (lung lining), peritoneum (abdominal lining), pericardium (heart sac), or testes. Therefore, these studies highlight the anti-mesothelioma activity of Cela and demonstrate that Cela MPs are a promising inhalable medicine for MPM treatment. Cela MP was also able to retain the antioxidant activity of Cela only while mechanistic studies revealed triggered autophagy and an induction of apoptosis. Additionally, a 3D-spheroid study was performed where a single dose of Cela MP at 1.0 µM significantly inhibited spheroid growth. The therapeutic efficacy of Cela MPs was evaluated against four mesothelioma cell lines, where Cela MP exhibited significant reduction in IC 50 values, and blank MPs produced no toxicity to normal cells. A subsequent release study showed an initial burst release up to 59.9 ± 2.9%, followed by sustained release. The optimized Cela MPs exhibited high entrapment efficiency (72.8 ± 6.1%) and possessed a wrinkled surface with a mean geometric diameter of ~2 µm and an aerodynamic diameter of 4.5 ± 0.1 µm, suggesting them to be suitable for pulmonary delivery. In this study, we developed inhaled surface-modified Cela-loaded poly(lactic-co-glycolic) acid (PLGA) microparticles (Cela MPs) for the treatment of MPM using a double emulsion solvent evaporation method. Celastrol (Cela), a pentacyclic triterpenoid, has demonstrated promising therapeutic potential as an antioxidant, anti-inflammatory, neuroprotective agent, and anti-cancer agent. Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer affecting the pleural lining of the lungs. ![]()
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