Side effects often limit the use of doxorubicin (DOX) in cancer treatment. We have recently developed a nanostructured lipid carrier (NLC) formulation for synergistic chemotherapy, encapsulating DOX and the anticancer adjuvants docosahexaenoic acid (DHA) and α-tocopherol succinate (TS). Hydrophobic ion-pairing with TS allowed a high DOX entrapment in the nanocarrier. In this work, we investigated the pharmacokinetics of this formulation after intravenous administration in mice. The first data obtained led us to propose synthesizing covalent DOX-TS conjugates to increase DOX retention in the NLC. We successfully conjugated DOX to TS via an amide or hydrazone bond. In vitro studies in 4T1 tumor cells indicated low cytotoxicity of the amide derivative, while the hydrazone conjugate was effective in killing cancer cells. We encapsulated the hydrazone derivative in a DHA-based nanocarrier (DOX-hyd-TS/NLC), which had reduced particle size and high drug encapsulation efficiency. The pH-sensitive hydrazone bond allowed controlled DOX release from the NLC, with increased drug release at acidic conditions. In vivo studies revealed that DOX-hyd-TS/NLC had a better pharmacokinetic profile than free DOX and attenuated the short-term cardiotoxic effects caused by DOX, such as QT prolongation and impaired left ventricular systolic function. Moreover, this formulation showed excellent therapeutic performance by reducing tumor growth in 4T1 tumor-bearing mice and decreasing DOX-induced toxicity to the heart and liver, demonstrated by hematologic, biochemical, and histologic analyses. These results indicate that DOX-hyd-TS/NLC may be a promising nanocarrier for breast cancer treatment.
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http://dx.doi.org/10.1016/j.biopha.2021.112373 | DOI Listing |
Daru
December 2024
Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, POB 11795, Egypt.
Background: Bile salts enriched nanovesicles (bilosomes) have been attention worthy in the past few years due to their distinctive effect on the enhancement of drug delivery through various physiological administration routes. Oral delivery of multifunctioning phytochemical curcumin has faced a lot of difficulties due to its scarce solubility and poor oral bioavailability.
Objective: The current investigation aimed to develop curcumin loaded bilosomes for improvement of oral curcumin bioavailability with maximum efficiency and safety.
ACS Appl Bio Mater
December 2024
Discipline of Pharmaceutical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4300, South Africa.
Bacterial infections pose an increasingly worrisome threat to the health of humankind, with antibiotic resistance contributing significantly to this burden. With current conventional antibiotics perpetuating the problem, and a paucity in developing antibiotics, drug delivery systems incorporating nanotechnology appear promising. As such, a dual enzyme-responsive multifunctional nanostructured lipid carrier (NLC) incorporating farnesol (FAN) and triglycerol monostearate (TGMS), was conceptualized for the codelivery of vancomycin (VCM) and antimicrobial peptide (AMP) to enhance the antibacterial activity of VCM.
View Article and Find Full Text PDFNanoscale
December 2024
School of Science, College of STEM, RMIT University, Melbourne, Victoria 3000, Australia.
Innovations in nanostructured surfaces have found a practical place in the medical area with use in implant materials for post-operative infection prevention. These textured surfaces should be dual purpose: (1) bactericidal on contact and (2) resistant to biofilm formation over prolonged periods. Here, hydrothermally etched titanium surfaces were tested against two highly antimicrobial resistant microbial species, methicillin-resistant and .
View Article and Find Full Text PDFJ Nanobiotechnology
December 2024
Department of Joint Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, 250021, People's Republic of China.
Osteoarthritis (OA) is the most common disease in aging joints and has characteristics of cartilage destruction and inflammation. It is currently considered a metabolic disease, and the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes plays a crucial catabolic regulatory role in its pathogenesis. Targeting of this axis in chondrocytes may provide a therapeutic approach for OA treatment.
View Article and Find Full Text PDFACS Nano
December 2024
Center for Cellular and Molecular Diagnostics, Tulane University School of Medicine, New Orleans, Louisiana 70112, United States.
Spatial omics methods are extensions of traditional histological methods that can illuminate important biomedical mechanisms of physiology and disease by examining the distribution of biomolecules, including nucleic acids, proteins, lipids, and metabolites, at microscale resolution within tissues or individual cells. Since, for some applications, the desired resolution for spatial omics approaches the nanometer scale, classical tools have inherent limitations when applied to spatial omics analyses, and they can measure only a limited number of targets. Nanotechnology applications have been instrumental in overcoming these bottlenecks.
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