{'fraction_non_alphanumeric': 0.022779043280182234, 'fraction_numerical': 0.0, 'mean_word_length': 6.200819672131147, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Improving Drug Delivery of Micellar Paclitaxel against Non-Small Cell Lung Cancer by Coloading Itraconazole as a Micelle Stabilizer and a Tumor Vascular Manipulator.

Although polymeric micelles of paclitaxel (PTX) significantly reduce excipient-induced toxicity compared with Taxol, they exhibit few clinical advantages in tumor inhibition and overall survival. To improve, itraconazole (ITA), an antifungal drug with potent anti-angiogenesis activity, is co-encapsulated together with PTX within the PEG-PLA micelles. The strong intermolecular interactions between the payloads inhibit drug crystallization and prevent drugs from binding with external proteins, render super-stable micelles upon dilution and exposure to biological environment, and enter the tumor cells through endocytosis. The co-encapsulated micelles show strong anti-proliferation potency against non-small-cell lung cancer (NSCLC) and even PTX resistant NSCLC cells in vitro and significantly improve the drug accumulation within the tumor in vivo. Compared with PTX monotherapy or combination therapy using individual PTX and ITA micelles, the co-encapsulated micelle demonstrates strikingly superior efficacy in tumor growth inhibition, recurrence prevention, and reversion of PTX resistance, in Kras mutant patient derived xenografts, orthotropic models, and paclitaxel-resistance subcutaneous models. Besides the pharmacokinetic improvement, therapeutic benefits are also contributed by angiogenesis inhibition and blood vessel normalization by ITA. Utilizing the pharmaceutical and pharmacological synergies between the therapeutic agents, a simple yet effective design of a combination cancer nanomedicine that is industrially scalable and clinically translatable is achieved.