Unlabelled: The anticancer nanodrug Doxil®, a pegylated liposomal doxorubicin (PLD), accumulates at the tumor site due to the enhanced permeability and retention effect. However, the mechanism of doxorubicin release from the liposome within the tumor is unknown. We propose that ammonia produced at the tumor site by glutaminolysis enhances release. Using tumor cells in culture, we show that PLD, when ammonia is present, kills tumor cells with an efficacy similar to that of free doxorubicin, while PLD without ammonia and ammonia without PLD have very poor cytotoxicity. We confirm in tumor mouse models that ammonium/ammonia levels measured at the tumors are in the millimolar range, much higher than in the plasma of these mice. This is a new concept of stimulus-response, therapeutically efficacious drug release in tumors, with ammonia derived from tumor cell glutaminolysis acting as the stimulus. There may also be additional microenvironment-related variables that influence therapeutic efficacy.
From The Clinical Editor: The use of liposomal platform as a drug carrier has brought success to Doxil. Nonetheless, the underlying mechanism of drug release at tumor site and subsequent tumor killing was largely unknown. In this article, the authors demonstrated in their experiments that higher ammonia level in the tumor environment was the main mechanism for drug release.
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http://dx.doi.org/10.1016/j.nano.2015.06.007 | DOI Listing |
Front Bioeng Biotechnol
January 2025
Pharmaceutical Development Biologicals, TIP, Boehringer Ingelheim Pharma GmbH & Co., KG, Innovation Unit, Biberach an der Riss, Germany.
Polysorbates, in particular polysorbate (PS) 20 and 80, are the most commonly used surfactants for stabilising biotherapeutics produced by biotechnological processes. PSs are derived from ethoxylated sorbitan (a derivative of sorbitol) esterified with fatty acids of varying chain length and degree of saturation. In the past, these surfactants have been reported to have specific liabilities.
View Article and Find Full Text PDFFront Bioeng Biotechnol
January 2025
Federal University of Alagoas, Center of Technology, Maceió, Brazil.
Medical implants are designed to replace missing parts or improve body functions and must be capable of providing structural support or therapeutic intervention for a medical condition. Advances in materials science have enabled the development of devices made from metals, polymers, bioceramics, and composites, each with its specific advantages and limitations. This review analyzes the incorporation of biopolymers, proteins, and other biomacromolecules into implants, focusing on their role in biological integration and therapeutic functions.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
Department of Mechanical Engineering, Chang Gung University, Taoyuan, 33302, Taiwan.
Background: In clinical practice, imiquimod is used to treat Human Papillomavirus (HPV)-related lesions, such as condyloma and Cervical Intraepithelial Neoplasia (CIN). Metronidazole is the most commonly prescribed antibiotic for bacterial vaginosis. The study developed biodegradable imiquimod- and metronidazole-loaded nanofibrous mats and assessed their effectiveness for the topical treatment of cervical cancer, a type of HPV-related lesion.
View Article and Find Full Text PDFInt J Nanomedicine
January 2025
Department of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.
Background: Melanoma is an aggressive form of skin cancer, and single-modality treatments often fail to prevent tumor recurrence and metastasis. Combination therapy has emerged as an effective approach to improve treatment outcomes.
Methods: In this study, we developed a multifunctional nanoplatform, MIL@DOX@ICG, utilizing MIL-101-NH(Fe) as a carrier to co-deliver the chemotherapeutic agent doxorubicin (DOX) and the photosensitizer indocyanine green (ICG).
Int J Nanomedicine
January 2025
School of Pharmacy, Ningxia Medical University, Yinchuan, 750004, People's Republic of China.
Objective: This study focuses on the development and evaluation of nanostructured lipid carriers (NLCs) loaded with aloperine as a potential therapeutic approach for the treatment of pulmonary arterial hypertension.
Methods: The NLCs were designed to enhance the solubility, stability, and bioavailability of aloperine, a compound with vasodilatory and anti-inflammatory properties. Through a series of experiments including single-factor experimentation, transmission electron microscopy, high-performance liquid chromatography, in vivo pharmacokinetics, and tissue distribution studies, we assessed the physicochemical properties, drug release profiles, and in vitro and in vivo performance of this novel nanocarrier.
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