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Liposomal encapsulation of cholecalciferol mitigates in vivo toxicity and delays tumor growth

Published on Friday, 11 July 2025

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Discussion: 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.

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About this publication.

The Di Bella's Method: Use of Vitamin D analogues and/or derivatives with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Breast and Prostate Cancer:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Dihydrotachysterol, Alfacalcidol, synthetic Vitamin D3);

- Vitamin D (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Omega 3 Essential/Unsaturated Fatty Acids. From 1.5 grams up to 3.0 grams per day orally);

The Di Bella's Method: Use of Vitamin D analogues and/or derivatives with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds - in several Oncological Pathologies:

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;