Parenteral chemotherapy is usually administered intravenously, although patient preference and health economics suggest the subcutaneous (sc) route could be an attractive alternative. However, due to the low aqueous solubility of hydrophobic drugs and injection volume limitations, the total amount of drug that can be administered in a single sc injection is frequently insufficient. We have developed hyaluronidase coated nanoparticles (NPs) that efficiently encapsulate such drugs, thus addressing both issues and allowing sufficient amounts of hydrophobic drug to be administered and absorbed effectively. CUDC-101, a poorly water-soluble multitargeted anticancer drug that simultaneously inhibits the receptor tyrosine kinases (RTKs) EGFR and HER2, as well as histone deacetylase (HDAC), was encapsulated in polymeric Molecular Envelope Technology (MET) NPs. The role of polymer chemistry, formulation parameters, and coating with hyaluronidase (HYD) on MET-CUDC-101 NP formulations was examined and optimized to yield high drug loading and colloidal stability, and, after freeze-drying, stable storage at room temperature for up to 90 days. The pharmacokinetic studies in healthy rats showed that plasma AUC after sc administration correlates tightly with formulation physical chemistry, specifically colloidal stability. Compared to uncoated NPs, the HYD-coating doubled the drug plasma exposure. In a murine A431 xenograft model, the coated HYD-MET-CUDC-101 NPs at a dose equivalent to 90 mg kg CUDC-101 increased the survival time from 15 days (control animals treated with hyaluronidase alone) to 43 days. Polymer MET nanoparticles coated with hyaluronidase enabled the subcutaneous delivery of a hydrophobic drug with favorable therapeutic outcomes.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00294 | DOI Listing |
J Control Release
January 2025
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu 610031, PR China. Electronic address:
Int J Biol Macromol
December 2024
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300350, PR China. Electronic address:
Exosomes as a unique drug delivery system provide a new choice for tumor therapy. However, the in vitro functionalization of exosomes and the process of circulating drug delivery can easily cause exosome degradation and drug loss, thus reducing the efficiency of drug delivery. In this work, based on the endocyto-fusion-exocytosis pathway of exosome formation, a multifunctional hyaluronic acid nanogel loaded with the antiangiogenic drug vatalanib and the near-infrared photothermal agent indocyanine green (ICG) was designed.
View Article and Find Full Text PDFFront Oncol
December 2024
Experimental Center for Teaching, Hebei Medical University, Shijiazhuang, Hebei, China.
Lung cancer, as a serious threat to human health and life, necessitating urgent treatment and intervention. In this study, we prepared hyaluronic acid (HA)-targeted topotecan liposomes for site-specific delivery to tumor cells. The encapsulation efficiency, stability, chemical structure, and morphology of HA-targeted topotecan liposomes were studied, and the release properties, cellular uptake capacity, and therapeutic efficacy of topotecan were further investigated.
View Article and Find Full Text PDFInt J Nanomedicine
September 2024
Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, 150081, People's Republic of China.
Adv Healthc Mater
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Intensive Care Unit, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518031, P. R. China.
Catheter-associated urinary tract infection (CAUTI) is a prevalent type of hospital-acquired infection, affecting approximately 15% to 25% of patients with urinary catheters. Long-term use of the catheter can lead to colonization of microorganisms and biofilm formation, and may develop into bacterial CAUTI. However, the frequent replacement of catheters in clinical settings can result in tissue damage, inflammation, ulceration, and additional complications, causing discomfort and pain for patients.
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