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Translation: Opportunities and Challenges
Published in Sourav Bhattacharjee, Principles of Nanomedicine, 2019
Protein-based NPs: Abraxane®: Marketed by Celgene Corporation (New Jersey, USA), it is a nanoparticulate albumin-bound formulation of paclitaxel conjugated to 130 nm albumin particles and indicated in solid tumors of breast, gut, head and neck, and gonads. Free paclitaxel lacks solubility, and, hence, cremophor EL or ethanol is used to improve solubility. However, these additives cause toxicity, including allergic reactions, in 20%–40% of the patients. Cremophor EL can form micellar structures of encapsulated paclitaxel with reduced clearance and a low volume of distribution [13–16]. Moreover, paclitaxel is quite toxic, causing a range of side effects, including hepatotoxicity and peripheral neuropathy. Conjugation with albumin improves solubility of paclitaxel while curtailing its side effects. Upon intravenous administration, the 130 nm albumin particles dissociate into ~8 nm particles while being coated by paclitaxel. In human trials, the maximum tolerated dose of Abraxane® was found to be 300–375 mg/m2 of body surface area compared to 175 mg/ m2 for cremophor EL–based formulations [17]. Abraxane® also showed adequate anticancer activity with reduced side effects compared to the cremophor EL formulations [18]. The advantages of Abraxane® over such cremophor EL–based formulations could be demonstrated for most of human tumor xenograft cancer models [19] of prostate [20], lung (non-small cell lung cancer) [21–24], breast (metastatic carcinoma) [25, 26], and ovary [27–30]. The results were most pronounced in breast cancer, where a significant increase in the intratumoral concentration of Abraxane®, compared to cremophor EL–based formulations, was observed. Abraxane® was approved in 2005 by the US Food and Drug Administration (FDA) and European Medicines Agency to treat refractory or relapsed breast cancer cases. From 2013, the US FDA has approved the use of Abraxane® in treating pancreatic cancer cases [31, 32] as a less toxic alternative to a FOLFIRINOXa regime.
Fabrication of polymer-based self-assembly nanocarriers loaded with a crizotinib and gemcitabine: potential therapeutics for the treatment of endometrial cancer
Published in Journal of Biomaterials Science, Polymer Edition, 2022
Jiaolin Yang, Hongrui Guo, Jing Lei, Sanyuan Zhang, Shaoguo Zhang, Jirong Bai, Sufen Li
Gemcitabine (GEM) is analogous to a nucleoside used to treat non-small-cell lung, pancreatic, bladder, and breast cancers as a kind of chemotherapy. In treating pancreatic cancer alone in weakened pancreatic cancer patients or conjunction with other medications including leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin, FOLFIRINOX in healthy pancreatic cancer patients, it is the chosen medicine of choice [29–31]. GEM is essential, but because of too quick metabolism, rapid renal clearance, and reduced protein binding, the shorter half life span is between 8 and 15 min [32–34]. GEM therapeutic levels require continuous parenteral delivery because of the short half-life, causing significant adverse effects such as renal and hematological toxicities. For an alternate drug delivery method, this inherent disadvantage was necessary. Also, in the treatment of advanced NSCLC, crizotinib (CRZ), a drug authorized by the German FDA, is suggested. CRZ inhibits anaplastic lymphoma kinase (ALK) and tyrosine kinases of hepatocyte receptor growth factor (C-MET) and leads to apoptosis by activating caspase-3. Since the early stages of research, CRZ has demonstrated exceptional effectiveness in ALK-positive NSCLC [35]. Despite its promise, however, the CRZ is not entirely successful after many administrations as patients develop resistance to this medication [36]. In addition, free CRZ as a hydrophobic drug may be predicted to have poor solubility and restricted blood circulation. Therefore, in lung cancer therapy, it is necessary to exceed these limitations and reach complete therapeutic potential [37].