1. Optimization and characterization of Rituximab targeted multidrug loaded cyclodextrin nanoparticles against Non-Hodgkin Lymphoma.
- Author
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Demirtürk N, Varan G, Kağa S, Malanga M, and Bilensoy E
- Subjects
- Humans, Cell Line, Tumor, Animals, Mice, Doxorubicin administration & dosage, Doxorubicin pharmacology, Doxorubicin chemistry, Vincristine administration & dosage, Vincristine pharmacology, Vincristine chemistry, Prednisone administration & dosage, Prednisone chemistry, Prednisone pharmacology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols chemistry, Cyclophosphamide administration & dosage, Cyclophosphamide pharmacology, Drug Resistance, Neoplasm drug effects, Hemolysis drug effects, Drug Carriers chemistry, Particle Size, Cellulose, Lymphoma, Non-Hodgkin drug therapy, Rituximab administration & dosage, Rituximab chemistry, Nanoparticles chemistry, Cyclodextrins chemistry, Drug Liberation, Cell Survival drug effects
- Abstract
Currently, Non-Hodgkin Lymphoma (NHL) constitutes 85-90 % of all lymphomas. Clinical treatment of NHL is based on the "4-drug regimen" known as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Rituximab (RTX) is added to increase the effectiveness and selectivity of the treatment and is the first-line standard treatment for NHL patients. However, success is often prevented by the development of drug resistance. In this study, it was aimed to overcome drug resistance by using two novel tumor-targeted derivatives: guanidine-amphiphilic cyclodextrin (ACD) and guanidine-cyclodextrin polymer (PCD) nanoparticles (NP). These constructs display promise in overcoming drug resistance and enhancing the effectiveness of R-CHOP treatment while potentially eliminating the need for corticosteroid. NP were found to be smaller than 200 nm by dynamic light scattering (DLS). Hemolytic activity and cytotoxicity data on L929 cells demonstrated the safety of the newly synthesized CD derivatives. Additional in vitro characterization studies, including surface charge, physical stability, drug loading capacity, drug release profile, and imaging, as well as conventional and 3D cell culture studies were carried out. Compared to drug solutions, the viability of Daudi human lymphoma cells was statistically significantly decreased in both drug-loaded ACD and PCD NP formulations (p < 0.05). Additionally, RTX-conjugated and drug-loaded ACD NPs exhibited the lowest cell viability due to RTX dependent cytotoxicity., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Erem Bilensoy reports financial support was provided by Scientific and Technological Research Council of Turkey. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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