Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model

Review Biochemistry & Molecular Biology

Efficacy and Safety of Topical Mechanistic Target of Rapamycin Inhibitors for Facial Angiofibromas in Patients with Tuberous Sclerosis Complex: A Systematic Review and Network Meta-Analysis

Yu-Ting Lin et al.

Summary: The study suggests that topical sirolimus, particularly at a concentration of 0.2%, is effective and safe for treating facial angiofibromas in patients with TSC.

BIOMEDICINES (2022)

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Article Biochemistry & Molecular Biology

Modulatory Effect of Diosmin and Diosmetin on Metalloproteinase Activity and Inflammatory Mediators in Human Skin Fibroblasts Treated with Lipopolysaccharide

Marcin Feldo et al.

Summary: This study investigated the effects of diosmin and diosmetin on modulating proinflammatory factor levels in human skin fibroblasts. The results showed that both flavonoids reduced levels of IL-6 and Il-1 beta as well as COX-2 and PGE2, with no impact on IL-10. The compounds were more effective when added prior to LPS stimulation, and diosmetin had a stronger modulating effect.

MOLECULES (2022)

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Article Cell Biology

mTORC1 Activity in Psoriatic Lesions Is Mediated by Aberrant Regulation through the Tuberous Sclerosis Complex

Antonio Ferreri et al.

Summary: Inflammatory cytokines regulate the TSC complex by inducing TSC2 phosphorylation, leading to degradation, and contribute to the pathogenesis of psoriasis.

CELLS (2022)

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Article Nanoscience & Nanotechnology

Topical Delivery of Rapamycin by Means of Microenvironment-Sensitive Core-Multi-Shell Nanocarriers: Assessment of Anti-Inflammatory Activity in an ex vivo Skin/T Cell Co-Culture Model

Fiorenza Rancan et al.

Summary: This study tested redox-sensitive CMS nanocarriers in an inflammatory skin model and found that they exert inhibitory effects on T cells after penetration across ex vivo skin, with superiority in drug delivery and downregulation of IL-2 release compared to other formulations. Overall, nanocarriers targeting diseased skin features show promise for improving the topical delivery of macrolide drugs.

INTERNATIONAL JOURNAL OF NANOMEDICINE (2021)

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Article Pharmacology & Pharmacy

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

Keerthana Rajes et al.

Summary: A synthetic route for redox-sensitive and non-sensitive core multi-shell (CMS) carriers with sizes below 20 nm was established. The study demonstrated the reducibility and drug release effect of reduction-sensitive CMS nanocarrier, showing significant release of model dye Nile red within 24 hours. Results also showed that the redox-sensitive CMS nanocarrier had higher drug release efficiency and encapsulation performance in ex vivo human skin experiments.

PHARMACEUTICS (2021)

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Article Biochemistry & Molecular Biology

Rapamycin Alleviates 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Aggravated Dermatitis in Mice with Imiquimod-Induced Psoriasis-Like Dermatitis by Inducing Autophagy

Hye Ran Kim et al.

Summary: Through mouse model experiments, we found that TCDD aggravated skin inflammation in IMQ-induced psoriatic mice, increasing the expression of AHR, CYP1A1, inflammatory cytokines, and oxidative stress markers while decreasing autophagy-related factors and antioxidant markers. Rapamycin, on the other hand, alleviated TCDD-induced skin inflammation and restored autophagy inhibition, AHR expression, oxidative stress, and inflammatory response in the psoriatic mouse model.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Food Science & Technology

Macrolides: From Toxins to Therapeutics

Kiersten D. Lenz et al.

Summary: Macrolides are a diverse class of compounds characterized by a macrocyclic lactone ring and variable side chains or groups. While some macrolides are toxins that disrupt natural cellular processes, others have therapeutic properties.

TOXINS (2021)

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Article Materials Science, Biomaterials

Oxidation-Sensitive Core-Multishell Nanocarriers for the Controlled Delivery of Hydrophobic Drugs

Keerthana Rajes et al.

Summary: The drug loading and release properties of oxidation-sensitive core-multishell (osCMS) nanocarriers were investigated, showing good loading capacity for anti-inflammatory drugs and photosensitizers. In vitro studies on oxidative processes demonstrated the potential for enhanced delivery of photosensitizers under oxidative stress conditions in human skin. The number and position of thioether groups influenced the physicochemical properties and drug delivery capabilities of the carriers.

ACS BIOMATERIALS SCIENCE & ENGINEERING (2021)

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Review Medicine, General & Internal

Recent Updates on the Involvement of PI3K/AKT/mTOR Molecular Cascade in the Pathogenesis of Hyperproliferative Skin Disorders

Laura Mercurio et al.

Summary: PI3K represents a family of kinases that control multiple biological processes in mammalian cells and is associated with various skin pathologies. The dysregulation of PI3K/AKT/mTOR pathway contributes to uncontrolled cell proliferation and resistance to apoptosis in skin cancers, while also leading to enhanced proliferation, defective differentiation, and anti-apoptosis in psoriasis. The role of PI3K/AKT/mTOR in atopic dermatitis is less characterized, with recent evidence highlighting its function in epidermal barrier formation and stratification.

FRONTIERS IN MEDICINE (2021)

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Article Chemistry, Multidisciplinary

Improved Skin Permeability after Topical Treatment with Serine Protease: Probing the Penetration of Rapamycin by Scanning Transmission X-ray Microscopy

Gregor Germer et al.

Summary: Drug penetration in human skin ex vivo following skin barrier modification was systematically studied using scanning transmission X-ray microscopy. Two methods, employing Beer-Lambert law and singular value decomposition, were compared for analyzing drug concentration data. Results showed that rapamycin did not penetrate the stratum corneum of untreated skin, but penetrated more efficiently after pretreatment with serine protease. The drug mainly associated with corneocytes, with less presence in the intercellular lipid compartment.

ACS OMEGA (2021)

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Review Dermatology

Systematic review of sirolimus in dermatological conditions

Andrew W. Swarbrick et al.

Summary: Sirolimus has shown promise in treating various dermatological conditions and is widely used in skincare. While it has demonstrated efficacy in certain areas, there are limitations that require further research to confirm its effectiveness.

AUSTRALASIAN JOURNAL OF DERMATOLOGY (2021)

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Review Biochemistry & Molecular Biology

Regulatory Macrophages and Tolerogenic Dendritic Cells in Myeloid Regulatory Cell-Based Therapies

Maaike Suuring et al.

Summary: Myeloid regulatory cell-based therapy, focusing on generating tolerogenic dendritic cells (tolDCs) and regulatory macrophages (Mregs), has shown great potential in organ transplantation and autoimmune diseases. These cells are produced ex vivo using various differentiation signals and stimuli, with studies in animals and humans leading to clinical trials for therapeutic applications.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Activation of mTORC1 in fibroblasts accelerates wound healing and induces fibrosis in mice

Xiao Hu et al.

WOUND REPAIR AND REGENERATION (2020)

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Article Immunology

Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases

Sijia Chen et al.

JOURNAL OF AUTOIMMUNITY (2020)

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Article Pharmacology & Pharmacy

Serine Protease-Mediated Cutaneous Inflammation: Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers

Janna Frombach et al.

PHARMACEUTICS (2020)

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Letter Dermatology

Successful Amelioration of Inflammatory Linear Verrucous Epidermal Nevus with Topical Sirolimus

Nayankumar Patel et al.

ANNALS OF DERMATOLOGY (2020)

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Article Materials Science, Biomaterials

Transdermal delivery of rapamycin with poor water-solubility by dissolving polymeric microneedles for anti-angiogenesis

Jinzhu Mao et al.

JOURNAL OF MATERIALS CHEMISTRY B (2020)

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Article Chemistry, Multidisciplinary

Core-multishell nanocarriers enhance drug penetration and reach keratinocytes and antigen-presenting cells in intact human skin

Janna Frombach et al.

JOURNAL OF CONTROLLED RELEASE (2019)

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Article Immunology

Mammalian Target of Rapamycin (mTOR) and the Proteasome Attenuates IL-1β Expression in Primary Mouse Cardiac Fibroblasts

May-Kristin Torp et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Dermatology

Targeting mTORC1/2 with OSI-027 inhibits proliferation and migration of keloid keratinocytes

Jun Chen et al.

EXPERIMENTAL DERMATOLOGY (2019)

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Article Chemistry, Physical

Protease-mediated Inflammation: An In Vitro Human Keratinocyte-based Screening Tool for Anti-inflammatory Drug Nanocarrier Systems

Janna Frombach et al.

ZEITSCHRIFT FUR PHYSIKALISCHE CHEMIE-INTERNATIONAL JOURNAL OF RESEARCH IN PHYSICAL CHEMISTRY & CHEMICAL PHYSICS (2018)

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Review Immunology

Epidermal mTORC1 Signaling Contributes to the Pathogenesis of Psoriasis and Could Serve as a Therapeutic Target

Claudia Buerger

FRONTIERS IN IMMUNOLOGY (2018)

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Article Chemistry, Multidisciplinary

Topically applied virus-like particles containing HIV-1 Pr55gag protein reach skin antigen-presenting cells after mild skin barrier disruption

Fiorenza Rancan et al.

JOURNAL OF CONTROLLED RELEASE (2017)

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Article Dermatology

Blocking mTOR Signalling with Rapamycin Ameliorates Imiquimod-induced Psoriasis in Mice

Claudia Buerger et al.

ACTA DERMATO-VENEREOLOGICA (2017)

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Review Immunology

mTORC1 signaling and IL-17 expression: Defining pathways and possible therapeutic targets

Wenkai Ren et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2016)

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Review Clinical Neurology

Topical Use of Mammalian Target of Rapamycin (mTOR) Inhibitors in Tuberous Sclerosis Complex-A Comprehensive Review of the Literature

Sergiusz Jozwiak et al.

PEDIATRIC NEUROLOGY (2016)

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Article Otorhinolaryngology

Rapamycin Inhibits Human Laryngotracheal Stenosis-derived Fibroblast Proliferation, Metabolism, and Function in Vitro

Daryan R. Namba et al.

OTOLARYNGOLOGY-HEAD AND NECK SURGERY (2015)

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Article Dermatology

Vertical inhibition of PI3K/Akt/mTOR signaling demonstrates in vitro and in vivo anti-fibrotic activity

Minrui Liang et al.

JOURNAL OF DERMATOLOGICAL SCIENCE (2014)

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Article Dermatology

Visible effects of rapamycin (sirolimus) on human skin explants in vitro

Antonio Peramo et al.

ARCHIVES OF DERMATOLOGICAL RESEARCH (2013)

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Article Oncology

Abstract 2501: Rapamycin inhibits epidermal cell proliferation in a xenograft model of tuberous sclerosis skin tumors

Shaowei Li et al.

CANCER RESEARCH (2011)

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Article Chemistry, Applied

Increased mass levels of certain serine proteases in the stratum corneum in acute eczematous atopic skin

R. Voegeli et al.

INTERNATIONAL JOURNAL OF COSMETIC SCIENCE (2011)

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Article Biochemistry & Molecular Biology

Mammalian target of rapamycin (mTOR) regulates TLR3 induced cytokines in human oral keratinocytes

Jiawei Zhao et al.

MOLECULAR IMMUNOLOGY (2010)

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Article Pharmacology & Pharmacy

New approach for local delivery of rapamycin by bioadhesive PLGA-carbopol nanoparticles

Weiwei Zou et al.

DRUG DELIVERY (2009)

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Article Immunology

External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers

Akiharu Kubo et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2009)

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Article Dermatology

Nanoparticle-Based Targeting of Vaccine Compounds to Skin Antigen-Presenting Cells By Hair Follicles and their Transport in Mice

Brice Mahe et al.

JOURNAL OF INVESTIGATIVE DERMATOLOGY (2009)

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Article Rheumatology

The PI3K/Akt/mTOR pathway in innate immune cells: emerging therapeutic applications

T. Weichhart et al.

ANNALS OF THE RHEUMATIC DISEASES (2008)

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Article Immunology

The TSC-mTOR Signaling Pathway Regulates the Innate Inflammatory Response

Thomas Weichhart et al.

IMMUNITY (2008)

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Article Immunology

Impact of mammalian target of rapamycin inhibition on lymphoid homing and tolerogenic function of nanoparticle-labeled dendritic cells following allogeneic hematopoietic cell transplantation

Wilfried Reichardt et al.

JOURNAL OF IMMUNOLOGY (2008)

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Article Multidisciplinary Sciences

Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation

Andrew Y. Choo et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Article Dermatology

Aberrant human tissue kallikrein levels in the stratum corneum and serum of patients with psoriasis: dependence on phenotype, severity and therapy

N. Komatsu et al.

BRITISH JOURNAL OF DERMATOLOGY (2007)

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Article Dermatology

Treatment of psoriasis with topical sirolimus: preclinical development and a randomized, double-blind trial

AD Ormerod et al.

BRITISH JOURNAL OF DERMATOLOGY (2005)

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Article Dermatology

Trypsin induces epidermal proliferation and inflammation in murine skin

U Meyer-Hoffert et al.

EXPERIMENTAL DERMATOLOGY (2004)

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Article Pharmacology & Pharmacy

Solubilization of rapamycin

P Simamora et al.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2001)

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Article Dermatology

The antipsoriatic activity of IL-10 is rather caused by effects on peripheral blood cells than by a direct effect on human keratinocytes

M Seifert et al.

ARCHIVES OF DERMATOLOGICAL RESEARCH (2000)

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Efficacy of topically applied rapamycin-loaded redox-sensitive nanocarriers in a human skin/T cell co-culture model

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