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Submitted: 23 Aug 2024
Revision: 29 May 2025
Accepted: 04 Jun 2025
ePublished: 28 Jun 2025
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Adv Pharm Bull. 2025;15(2): 371-389.
doi: 10.34172/apb.025.43681
  Abstract View: 149
  PDF Download: 32

Original Article

Codelivery of Raloxifene and Rutin as PEGylated Nanoliposomes: Formulation, Characterization, and Prophylactic Activity Against Breast Cancer

Maryam Abdulmaged Oleiwi 1 ORCID logo, Ali Al-Samydai 1* ORCID logo, Aya Y. Al-Kabariti 2 ORCID logo, Khaldun M. Al Azzam 3 ORCID logo, Simone Carradori 4 ORCID logo, Walhan Alshaer 5 ORCID logo

1 Pharmacological and Diagnostic Research Centre, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
2 Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Al-Ahliyya Amman University, Amman 19328, Jordan
3 Department of Chemistry, Faculty of Science, The University of Jordan, 11942, Amman, Jordan
4 Dipartimento di Farmacia, Università degli Studi Gabriele d’Annunzio Chieti-Pescara, Via dei Vestini 31, Chieti 66100, Italy.
5 Cell Therapy Center, The University of Jordan, 11942, Amman, Jordan
*Corresponding Author: Ali Al-Samydai, Email: a.alsamydai@ammanu.edu.jo

Abstract

Purpose: Breast cancer is the leading cause of cancer-related deaths among women. Chemotherapy faces challenges such as systemic toxicity and multidrug resistance. Advances in nanotechnology have led researchers to develop safer and more efficient cancer treatment methods.

Methods: The thin-film hydration method was employed to synthesize PEGylated nanoliposomes (NLs) loaded with raloxifene (RLX) and a combination of RLX and rutin. The NLs were characterized using a Zetasizer® instrument, transmission electron microscopy (TEM), and high-performance liquid chromatography (HPLC) analysis. The encapsulation of RLX and rutin was confirmed, and cell viability assays were conducted against breast cancer and normal endothelial cell lines.

Results: The encapsulation efficiency significantly increased in the mixed formulation, with RLX reaching 91.28% and rutin 78.12%, indicating successful encapsulation. These NLs remained stable for up to two months at room temperature and one month at 4°C, demonstrating a biphasic release pattern. After 24 hours, approximately 17% of RLX was released from the NLs and 25% from the mixed NLs. In contrast, 55% of rutin was released from the NLs and 70.4% from the mixed NLs within 72 hours. The inclusion of rutin or RLX in the liposomal formulation reduced cytotoxicity against breast cancer cell lines, as indicated by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. However, it improved safety in normal human cells and tissues.

Conclusion: PEGylated NLs loaded with RLX and rutin demonstrated safe anti-breast cancer effects, outperforming mixed NLs, suggesting the potential for a safer and more targeted treatment. Further investigations are needed into clinical translation.


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