Ameliorative anticancer effect of dendrimeric peptide modified liposomes of letrozole: In vitro and in vivo performance evaluations.

Autor: Hegde AR; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India; Department of Pharmaceutics, Faculty of Pharmacy, M.S. Ramaiah University of Applied Sciences, Gnanagangothri Campus, New B.E.L. Road, M.S.R. Nagar, M.S.R.I.T Post, Bengaluru, Karnataka, India., Paul M; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, Telangana State, India., Kumbham S; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, Telangana State, India., Roy AA; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India., Ahmad SF; Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia., Parekh H; School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba, Queensland 4102, Australia., Biswas S; Department of Pharmacy, Birla Institute of Technology & Science-Pilani, Hyderabad Campus, Medchal, Hyderabad 500078, Telangana State, India., Mutalik S; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India. Electronic address: ss.mutalik@manipal.edu.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2023 Dec 15; Vol. 648, pp. 123582. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1016/j.ijpharm.2023.123582
Abstrakt: Letrozole (LTZ) loaded dendrimeric nano-liposomes were prepared for targeted delivery to breast cancer cells. Surface modification with cationic peptide dendrimers (PDs) and a cancer specific ligand, transferrin (Tf), was attempted. Arginine-terminated PD (D-1) and Arginine-terminated, lipidated PD (D-2) were synthesized using Solid Phase Peptide Synthesis, purified by preparative HPLC and characterized using 1 HNMR, MS and DSC analyses. Surface modification of drug loaded liposomes with Tf and/or PD was carried out. Formulations were characterized using FTIR, DSC, 1 HNMR, XRD and TEM. Tf-conjugated LTZ liposomes (LTf) and Tf/D-2-conjugated LTZ liposomes (LTfD-2) showed greater cytotoxic potential (IC 50  = 95.03 µg/mL and 23.75 µg/mL respectively) with enhanced cellular uptake in MCF7 cells compared to plain LTZ. Blocking studies of Tf (Tf-receptor mediated internalization) revealed decreased uptake of LTf and LTfD-2 confirming the role of Tf in uptake of Tf-conjugated liposomes. Intravenous treatment with LTfD-2 caused highest reduction in tumor volumes of female BALB/c-nude mice (145 mm 3 ) compared to plain LTZ (605 mm 3 ) and unconjugated LTZ liposomes (LP) (300 mm 3 ). In vivo biodistribution studies revealed higher fluorescence in tumor tissue and liver of LTfD-2 treated mice than LTf or LP treatment. Immunohistochemical studies revealed greater apoptotic potential of LTfD-2 as indicated by TUNEL assay and ROS detection assay. The study reveals the superior therapeutic efficacy of the developed LTZ liposomal nanocarriers using PDs to enhance the transfection efficiency in addition to modifying the surface characteristics by attaching a targeting ligand for active drug targeting to breast cancer cells.
Competing Interests: Declaration of Competing Interest The authors 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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