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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Nutritional Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1529007
This article is part of the Research Topic Community Series in : The Role of Vitamin D as an Immunomodulator - Volume II View all 5 articles

Liposomal Encapsulation of Cholecalciferol Mitigates In Vivo Toxicity and Delays Tumor Growth

Provisionally accepted
Miriam Ezcurra Hualde Miriam Ezcurra Hualde 1Sara Zalba Sara Zalba 2Ángela Bella Ángela Bella 1Leire Arrizabalaga Leire Arrizabalaga 1Aline Risson Aline Risson 1Román García-Fuentes Román García-Fuentes 1Celia Gomar Celia Gomar 1Nuria Ardaiz Nuria Ardaiz 1Virginia Belsue Virginia Belsue 1David Ruiz-Guillamon David Ruiz-Guillamon 1Alejandro Serrano-Alcaide Alejandro Serrano-Alcaide 2Ainara Salgado Ainara Salgado 2Fernando Aranda Vega Fernando Aranda Vega 1Maria J Garrido Maria J Garrido 2Pedro Berraondo Pedro Berraondo 3*
  • 1 Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Navarre, Spain
  • 2 Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy and Nutrition, University of Navarra, Pamplona, Navarre, Spain
  • 3 Gene Therapy and Hepatology, Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, Navarra, Spain

The final, formatted version of the article will be published soon.

    Vitamin D3 (cholecalciferol) has demonstrated potential anticancer properties, but its clinical application is limited by associated toxicity at effective doses. This study investigated the use of liposomal encapsulation to increase the therapeutic efficacy of vitamin D3 while mitigating its toxicity. Liposomal vitamin D3 (VD-LP) was prepared via the film-hydration method and characterized for particle size, polydispersity index, encapsulation efficiency, and long-term stability. In vitro gene expression modulation was evaluated in monocytic THP-1 cells, and antiproliferative effects were assessed in HT29 (colorectal), BT474 (breast), and TRAMP-C1 (prostate) cancer cell lines. In vivo antitumor efficacy and toxicity were tested in a mouse model with subcutaneously implanted MC38 tumors. Tumor growth, survival rates, and serum calcium and phosphate levels were analyzed. VD-LP demonstrated high encapsulation efficiency and stability over 90 days, with a consistent particle size of approximately 83 nm. VD-LP modulated immune-related and metabolic gene expression in THP-1 cells, including upregulation of antimicrobial peptides and vitamin D receptor genes. VD-LP showed superior antiproliferative effects compared to free vitamin D3 in all tested cancer cell lines. In vivo, VD-LP delayed tumor growth and improved survival without causing hypercalcemia, highlighting its favorable toxicity profile. Liposomal encapsulation of vitamin D3 significantly improves its anticancer efficacy while mitigating toxicity, making it a promising strategy for future cancer therapies. VD-LP shows potential for enhanced therapeutic applications with reduced adverse effects, warranting further clinical exploration.

    Keywords: Liposomal encapsulation, Vitamin D3, Anticancer efficacy, Gene Expression, Tumor growth

    Received: 15 Nov 2024; Accepted: 10 Jan 2025.

    Copyright: © 2025 Ezcurra Hualde, Zalba, Bella, Arrizabalaga, Risson, García-Fuentes, Gomar, Ardaiz, Belsue, Ruiz-Guillamon, Serrano-Alcaide, Salgado, Aranda Vega, Garrido and Berraondo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Pedro Berraondo, Gene Therapy and Hepatology, Program of Immunology and Immunotherapy, Cima Universidad de Navarra, Pamplona, 31008, Navarra, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.