Ciprofloxacin Derivative-Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer.

Autor: Naguib YW; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA.; Department of Pharmaceutics, Minia University, Minia, 61519, Egypt., Alhaj-Suliman SO; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA., Wafa EI; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA., Saha S; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA., Ebeid K; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA.; Department of Pharmaceutics, Minia University, Minia, 61519, Egypt., Mohammed HHH; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt., Abdel-Rahman SA; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA., Abuo-Rahma GEA; Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt., Geary SM; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA., Salem AK; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA, 52242, USA.; Holden Comprehensive Cancer Center, University of Iowa Hospitals & Clinics, Iowa City, IA, 52242, USA.
Jazyk: angličtina
Zdroj: Small (Weinheim an der Bergstrasse, Germany) [Small] 2024 Oct; Vol. 20 (41), pp. e2302931. Date of Electronic Publication: 2023 Jul 31.
DOI: 10.1002/smll.202302931
Abstrakt: Combinations of chemotherapeutic agents comprise a clinically feasible approach to combat cancers that possess resistance to treatment. Type II endometrial cancer is typically associated with poor outcomes and the emergence of chemoresistance. To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative-loaded PEGylated polymeric nanoparticles (CIP2b-NPs) and paclitaxel (PTX) against human type-II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC 50 of PTX and increased G2/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co-administered with PTX. In addition, the co-delivery of CIP2b-NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry was normal, confirming the absence of any apparent off-target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b-NPs and PTX exhibits superior therapeutic activity in targeting human type-II endometrial cancer.
(© 2023 The Authors. Small published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
Externí odkaz: