Optimization and characterization of Rituximab targeted multidrug loaded cyclodextrin nanoparticles against Non-Hodgkin Lymphoma.

Autor: Demirtürk N; Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. Electronic address: eremino@hacettepe.edu.tr., Varan G; Department of Vaccine Technology, Vaccine Institute, Hacettepe University, 06100 Ankara, Turkey., Kağa S; Department of Biomedical Engineering, Faculty of Engineering, Afyon Kocatepe University, 03300 Afyon, Turkey., Malanga M; CarboHyde Zrt., Berlini u. 47-49, 1045 Budapest, Hungary., Bilensoy E; Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Sep 05; Vol. 662, pp. 124488. Date of Electronic Publication: 2024 Jul 18.
DOI: 10.1016/j.ijpharm.2024.124488
Abstrakt: 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.)
Databáze: MEDLINE
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