D-α-Tocopherol-Based Micelles for Successful Encapsulation of Retinoic Acid

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Published on Wednesday, 07 April 2021

Abstract

All-trans-retinoic acid (ATRA) represents the first-choice treatment for several skin diseases, including epithelial skin cancer and acne. However, ATRA's cutaneous side effects, like redness and peeling, and its high instability limit its efficacy.

To address these drawbacks and to improve ATRA solubilization, we prepared ATRA-loaded micelles (ATRA-TPGSs), by its encapsulation in D-α-tocopheryl-polyethylene-glycol-succinate (TPGS).

First, to explore the feasibility of the project, a solubility study based on the equilibrium method was performed; then, six ATRA-TPGS formulations were prepared by the solvent-casting method using different TPGS amounts. ATRA-TPGSs showed small sizes (11-20 nm), low polydispersity, slightly negative zeta potential, and proved good encapsulation efficiency, confirmed by a chemometric-assisted Fourier transform infrared spectroscopy (FTIR) investigation. ATRA-TPGS stability was also investigated to choose the most stable formulation. Using Carbopol® 980 as gelling agent, ATRA-TPGS-loaded gels were obtained and analyzed for their rheological profiles. Ex vivo release studies from ATRA-TPGSs were performed by Franz cells, demonstrating a permeation after 24 h of 22 ± 4 µ cm-2.

ATRA-TPGSs showed enhanced cytotoxic effects on melanoma cells, suggesting that these formulations may represent a valid alternative to improve patient compliance and to achieve more efficacious therapeutic outcomes.

 

About this publication.

See also:

- Official Web Site: The Di Bella Method;


 


- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (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);


 


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- 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;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

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

- 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;

- 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.