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

2021 ◽  
Vol 14 (3) ◽  
pp. 212
Author(s):  
Guendalina Zuccari ◽  
Sara Baldassari ◽  
Silvana Alfei ◽  
Barbara Marengo ◽  
Giulia Elda Valenti ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Skin Diseases ◽  
Ex Vivo ◽  
Gelling Agent ◽  
Glycol Succinate ◽  
Cutaneous Side Effects ◽  
Solubility Study ◽  
All Trans Retinoic Acid ◽  
First Choice ◽  
20 Nm

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.

scholarly journals Treatment With a New Synthetic Retinoid, Am80, of Acute Promyelocytic Leukemia Relapsed From Complete Remission Induced by All-trans Retinoic Acid

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 967-973 ◽  
Author(s):  
Tadasu Tobita ◽  
Akihiro Takeshita ◽  
Kunio Kitamura ◽  
Kazunori Ohnishi ◽  
Mitsuaki Yanagi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Major Advance ◽  
Synthetic Retinoid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
First Choice

Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a second CR with a second course of ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approximately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor-γ. Patients received Am80, 6 mg/m2, orally alone daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from the last ATRA therapy was not different between CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse events included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy.

Migratory properties of ex vivo expanded regulatory T cells: Influence of all-trans retinoic acid and rapamycin

2017 ◽  
Vol 45 ◽  
pp. 29-34 ◽  
Author(s):  
J.L. Beermann ◽  
C.T. Thiesler ◽  
U. Dringenberg ◽  
C. Alter ◽  
S. Kuhs ◽  
...  
Keyword(s):  
T Cells ◽  
Retinoic Acid ◽  
Regulatory T Cells ◽  
Ex Vivo ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals All-trans Retinoic Acid Disrupts Development in Ex Vivo Cultured Fetal Rat Testes. II: Modulation of Mono-(2-ethylhexyl) Phthalate Toxicity

2018 ◽  
Vol 168 (1) ◽  
pp. 149-159
Author(s):  
Daniel J Spade ◽  
Susan J Hall ◽  
Jeremy D Wortzel ◽  
Gerardo Reyes ◽  
Kim Boekelheide
Keyword(s):  
Retinoic Acid ◽  
Ex Vivo ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Fetal Rat ◽  
Ethylhexyl Phthalate

scholarly journals All-trans-Retinoic Acid Imprints Expression of the Gut-Homing Marker α4β7 while Suppressing Lymph Node Homing of Dendritic Cells

2013 ◽  
Vol 20 (10) ◽  
pp. 1642-1646 ◽  
Author(s):  
Tristan I. Evans ◽  
R. Keith Reeves
Keyword(s):  
Dendritic Cells ◽  
Retinoic Acid ◽  
Lymph Node ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Atra Treatment ◽  
Lymph Node Homing ◽  
All Trans Retinoic Acid ◽  
Trafficking Receptor ◽  
Dose Dependent

ABSTRACTTissue-directed trafficking of dendritic cells (DCs) as natural adjuvants and/or direct vaccine carriers is highly attractive for the next generation of vaccines and immunotherapeutics. Since these types of studies would undoubtedly be first conducted using nonhuman primate models, we evaluated the ability of all-trans-retinoic acid (ATRA) to induce gut-homing α4β7 expression on rhesus macaque plasmacytoid and myeloid DCs (pDCs and mDCs, respectively). Induction of α4β7 occurred in both a time-dependent and a dose-dependent manner with up to 8-fold increases for mDCs and 2-fold increases for pDCs compared to medium controls. ATRA treatment was also specific in inducing α4β7 expression, but not expression of another mucosal trafficking receptor, CCR9. Unexpectedly, upregulation of α4β7 was associated with a concomitant downregulation of CD62L, a marker of lymph node homing, indicating an overall shift in the trafficking repertoire. These same phenomena occurred with ATRA treatment of human and chimpanzee DCs, suggesting a conserved mechanism among primates. Collectively, these data serve as a first evaluation forex vivomodification of primate DC homing patterns that could later be used in reinfusion studies for the purposes of immunotherapeutics or mucosa-directed vaccines.

scholarly journals Redox-Responsive Nanocarrier for Controlled Release of Drugs in Inflammatory Skin Diseases

Pharmaceutics ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 37
Author(s):  
Keerthana Rajes ◽  
Karolina A. Walker ◽  
Sabrina Hadam ◽  
Fatemeh Zabihi ◽  
Fiorenza Rancan ◽  
...  
Keyword(s):  
Fluorescent Dyes ◽  
Skin Diseases ◽  
Ex Vivo ◽  
Nile Red ◽  
Redox Potentials ◽  
Inflammatory Skin Diseases ◽  
Molecular Weights ◽  
Molecular Weight Distributions ◽  
Redox Responsive ◽  
20 Nm

A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm and narrow molecular weight distributions was established. Cyclic voltammetric measurements were conducted characterizing the redox potentials of reduction-sensitive CMS while showcasing its reducibility through glutathione and tris(2-carboxyethyl)-phosphine as a proof of concept. Measurements of reduction-initiated release of the model dye Nile red by time-dependent fluorescence spectroscopy showed a pronounced release for the redox-sensitive CMS nanocarrier (up to 90% within 24 h) while the non-sensitive nanocarriers showed no release in PBS. Penetration experiments using ex vivo human skin showed that the redox-sensitive CMS nanocarrier could deliver higher percentages of the loaded macrocyclic dye meso-tetra (m-hydroxyphenyl) porphyrin (mTHPP) to the skin as compared to the non-sensitive CMS nanocarrier. Encapsulation experiments showed that these CMS nanocarriers can encapsulate dyes or drugs with different molecular weights and hydrophobicity. A drug content of 1 to 6 wt% was achieved for the anti-inflammatory drugs dexamethasone and rapamycin as well as fluorescent dyes such as Nile red and porphyrins. These results show that redox-initiated drug release is a promising strategy to improve the topical drug delivery of macrolide drugs.

scholarly journals All-Trans Retinoic Acid Modulates TLR4/NF-κB Signaling Pathway Targeting TNF-αand Nitric Oxide Synthase 2 Expression in Colonic Mucosa during Ulcerative Colitis and Colitis Associated Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Hayet Rafa ◽  
Sarra Benkhelifa ◽  
Sonia AitYounes ◽  
Houria Saoula ◽  
Said Belhadef ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Retinoic Acid ◽  
Signaling Pathway ◽  
Colonic Mucosa ◽  
Ex Vivo ◽  
Current Therapy ◽  
No Production ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Colitis associated cancer (CAC) is the colorectal cancer (CRC) subtype that is associated with bowel disease such as ulcerative colitis (UC). The data on role of NF-κB signaling in development and progression of CAC were derived from preclinical studies, whereas data from human are rare. The aim of this work was to study the contribution of NF-κB pathway during UC and CAC, as well as the immunomodulatory effect of all-trans retinoic acid (AtRA). We analyzed the expression of NOS2, TNF-α, TLR4, and NF-κB, in colonic mucosa. We also studied NO/TNF-αmodulation by LPS in colonic mucosa pretreated with AtRA. A marked increase in TLR4, NF-κB, TNF-α, and NOS2 expression was reported in colonic mucosa. The relationship between LPS/TLR4 and TNF-α/NO production, as well as the role of NF-κB signaling, was confirmed by ex vivo experiments and the role of LPS/TLR4 in NOS2/TNF-αinduction through NF-κB pathway was suggested. AtRA downregulates NOS2 and TNF-αexpression. Collectively, our study indicates that AtRA modulates in situ LPS/TLR4/NF-κB signaling pathway targeting NOS2 and TNF-αexpression. Therefore, we suggest that AtRA has a potential value in new strategies to improve the current therapy, as well as in the clinical prevention of CAC development and progression.

scholarly journals Olfactory Receptor OR7A17 Expression Correlates with All-Trans Retinoic Acid (ATRA)-Induced Suppression of Proliferation in Human Keratinocyte Cells

2021 ◽  
Vol 22 (22) ◽  
pp. 12304
Author(s):  
Hyeyoun Kim ◽  
See-Hyoung Park ◽  
Sae Woong Oh ◽  
Kitae Kwon ◽  
Se Jung Park ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Retinoic Acid ◽  
Skin Diseases ◽  
Retinoic Acid Receptor ◽  
Olfactory Receptors ◽  
Retinoid Signaling ◽  
Skin Cells ◽  
Human Keratinocyte ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Olfactory receptors (ORs), which belong to the G-protein-coupled receptor family, have been widely studied as ectopically expressed receptors in various human tissues, including the skin. However, the physiological functions of only a few OR types have been elucidated in skin cells. All-trans retinoic acid (ATRA) is a well-known medication for various skin diseases. However, many studies have shown that ATRA can have adverse effects, resulting from the suppression of cell proliferation. Here, we investigated the involvement of OR7A17 in the ATRA-induced suppression of human keratinocyte (HaCaT) proliferation. We demonstrated that OR7A17 is expressed in HaCaT keratinocytes, and its expression was downregulated by ATRA. The ATRA-induced downregulation of OR7A17 was attenuated via RAR α or RAR γ antagonist treatment, indicating that the effects of ATRA on OR7A17 expression were mediated through nuclear retinoic acid receptor signaling. Moreover, we found that the overexpression of OR7A17 induced the proliferation of HaCaT cells while counteracting the antiproliferative effect of ATRA. Mechanistically, OR7A17 overexpression reversed the ATRA-induced attenuation of Ca2+ entry. Our findings indicated that ATRA suppresses cell proliferation through the downregulation of OR7A17 via RAR α- and γ-mediated retinoid signaling. Taken together, OR7A17 is a potential therapeutic target for ameliorating the anti-proliferative effects of ATRA.

scholarly journals Treatment With a New Synthetic Retinoid, Am80, of Acute Promyelocytic Leukemia Relapsed From Complete Remission Induced by All-trans Retinoic Acid

Blood ◽  
1997 ◽  
Vol 90 (3) ◽  
pp. 967-973 ◽  
Author(s):  
Tadasu Tobita ◽  
Akihiro Takeshita ◽  
Kunio Kitamura ◽  
Kazunori Ohnishi ◽  
Mitsuaki Yanagi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Complete Remission ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Major Advance ◽  
Synthetic Retinoid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
First Choice

Abstract Differentiation therapy with all-trans retinoic acid (ATRA) has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). However, patients who relapse from ATRA-induced complete remission (CR) have difficulty in obtaining a second CR with a second course of ATRA therapy alone. We tested the efficacy of a new synthetic retinoid, Am80, in APL that had relapsed from CR induced by ATRA in a prospective multicenter study. Am80 is approximately 10 times more potent than ATRA as an in vitro differentiation inducer, is more stable to light, heat, and oxidation than ATRA, has a low affinity for cellular retinoic acid binding protein, and does not bind to retinoic acid receptor-γ. Patients received Am80, 6 mg/m2, orally alone daily until CR. Of 24 evaluable patients, 14 (58%) achieved CR. The interval from the last ATRA therapy was not different between CR and failure cases. The clinical response was well correlated with the in vitro response to Am80 in patients examined. Adverse events included 1 retinoic acid syndrome, 1 hyperleukocytosis, 9 xerosis, 8 cheilitis, 16 hypertriglyceridemia, and 15 hypercholesterolemia, but generally milder than those of ATRA, which all patients had received previously. Am80 is effective in APL relapsed from ATRA-induced CR and deserves further trials, especially in combination with chemotherapy.

scholarly journals RARγ is critical for maintaining a balance between hematopoietic stem cell self-renewal and differentiation

2006 ◽  
Vol 203 (5) ◽  
pp. 1283-1293 ◽  
Author(s):  
Louise E. Purton ◽  
Sebastian Dworkin ◽  
Gemma Haines Olsen ◽  
Carl R. Walkley ◽  
Stewart A. Fabb ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Knockout Mice ◽  
Ex Vivo ◽  
Retinoic Acid Receptor ◽  
Cell Types ◽  
Self Renewal ◽  
Hematopoietic Stem ◽  
All Trans Retinoic Acid ◽  
Ex Vivo Culture ◽  
Short Term Culture

Hematopoietic stem cells (HSCs) sustain lifelong production of all blood cell types through finely balanced divisions leading to self-renewal and differentiation. Although several genes influencing HSC self-renewal have been identified, to date no gene has been described that, when activated, enhances HSC self-renewal and, when activated, promotes HSC differentiation. We observe that the retinoic acid receptor (RAR)γ is selectively expressed in primitive hematopoietic precursors and that the bone marrow of RARγ knockout mice exhibit markedly reduced numbers of HSCs associated with increased numbers of more mature progenitor cells compared with wild-type mice. In contrast, RARα is widely expressed in hematopoietic cells, but RARα knockout mice do not exhibit any HSC or progenitor abnormalities. Primitive hematopoietic precursors overexpressing RARα differentiate predominantly to granulocytes in short-term culture, whereas those overexpressing RARγ exhibit a much more undifferentiated phenotype. Furthermore, loss of RARγ abrogated the potentiating effects of all-trans retinoic acid on the maintenance of HSCs in ex vivo culture. Finally, pharmacological activation of RARγ ex vivo promotes HSC self-renewal, as demonstrated by serial transplant studies. We conclude that the RARs have distinct roles in hematopoiesis and that RARγ is a critical physiological and pharmacological regulator of the balance between HSC self-renewal and differentiation.

Sign in / Sign up

Export Citation Format

Share Document