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Retinoids have proven performances in providing beneficial effects in a wide range of applications in the treatment of skin diseases, such as psoriasis, acne, actinic keratosis, and photoaging. Moreover, they induce differentiation of cancer cells and redirect them toward their normal phenotype, representing a valid tool for counteracting malignant lesions. Retinoids, in particular retinoic acid, have already marked an important advance in the treatment of acute promyelocytic leukemia, while other studies have proven their efficacy against a number of types of cancer cell lines (melanoma, neuroblastoma, prostate, and non-small cell lung carcinoma). Unfortunately, retinoids alone are unstable, as they are sensitive to oxygen, heat, and light. Furthermore, they are poorly soluble in water and often irritant. This Special Issue intends to provide examples of retinoid-loaded micro-nanodelivery systems as their utilization may decrease unwanted side effects, enhance drug solubility, provide sustained release, and exert drug protection against environmental agents. Thus, micro-nanodelivery systems modifying pharmacokinetics and bioavailability represent a valid approach in the treatment of Retinoids sensible disorders and diseases.

Dr. Guendalina Zuccari
Guest Editor

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Keywords

drug delivery systems
retinoic acid
fenretinide
liposomes
polymeric micelles
micro-nanosystems
cancer
topic applications

Published Papers (2 papers)

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Research

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26 pages, 4385 KiB

Open AccessArticle

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

by Guendalina Zuccari, Sara Baldassari, Silvana Alfei, Barbara Marengo, Giulia Elda Valenti, Cinzia Domenicotti, Giorgia Ailuno, Carla Villa, Leonardo Marchitto and Gabriele Caviglioli

Pharmaceuticals 2021, 14(3), 212; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14030212 - 04 Mar 2021

Cited by 25 | Viewed by 2820

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. Full article

(This article belongs to the Special Issue Applications of Micro-Nanosystems in Retinoids Delivery)

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Review

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15 pages, 2679 KiB

Open AccessReview

Retinoids Delivery Systems in Cancer: Liposomal Fenretinide for Neuroectodermal-Derived Tumors

by Veronica Bensa, Enzo Calarco, Elena Giusto, Patrizia Perri, Maria Valeria Corrias, Mirco Ponzoni, Chiara Brignole and Fabio Pastorino

Pharmaceuticals 2021, 14(9), 854; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14090854 - 26 Aug 2021

Cited by 8 | Viewed by 2491

Abstract

Retinoids are a class of natural and synthetic compounds derived from vitamin A. They are involved in several biological processes like embryogenesis, reproduction, vision, growth, inflammation, differentiation, proliferation, and apoptosis. In light of their important functions, retinoids have been widely investigated for their therapeutic applications. Thus far, their use for the treatment of several types of cancer and skin disorders has been reported. However, these therapeutic agents present several limitations for their widespread clinical translatability, i.e., poor solubility and chemical instability in water, sensitivity to light, heat, and oxygen, and low bioavailability. These characteristics result in internalization into target cells and tissues only at low concentration and, consequently, at an unsatisfactory therapeutic dose. Furthermore, the administration of retinoids causes severe side-effects. Thus, in order to improve their pharmacological properties and circulating half-life, while minimizing their off-target uptake, various retinoids delivery systems have been recently developed. This review intends to provide examples of retinoids-loaded nano-delivery systems for cancer treatment. In particular, the use and the therapeutic results obtained by using fenretinide-loaded liposomes against neuroectodermal-derived tumors, such as melanoma, in adults, and neuroblastoma, the most common extra-cranial solid tumor of childhood, will be discussed. Full article

(This article belongs to the Special Issue Applications of Micro-Nanosystems in Retinoids Delivery)

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