Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects

Siddique, Muhammad Irfan; Katas, Haliza; Jamil, Adawiyah; Amin, Mohd Cairul Iqbal Mohd; Ng, Shiow Fern; Zulfakar, Mohd Hanif; Nadeem, Syed Maaz

doi:10.1007/s13346-017-0439-7

Cited by 46 publications

(31 citation statements)

References 35 publications

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“…By demonstrating that EVOO phenols exert anti‐inflammatory effects on human keratinocytes, our study not only extends these previous findings to also encompass HTy‐Ac, but it shows that human keratinocytes are direct targets of EVOO phenols, which appears translationally interesting in the context of inflammatory skin disorders, as also encouraged by the mentioned studies investigating the potential use of olive oil‐derived compounds in the field of dermatology …”

Section: Discussionsupporting

confidence: 82%

“…In a mouse model of AD, HTy had beneficial effects, reducing erythema intensity and dermatitis and decreasing T‐helper cell cytokines in serum and skin, albeit only in the presence of hydrocortisone . Recently, a study evaluated the safety of a cream with hydrocortisone and HTy, showing that long‐term use had a favorable safety profile, a finding encouraging further clinical trials …”

Section: Discussionmentioning

confidence: 99%

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Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Aparicio‐Soto

Redhu

Sánchéz-Hidalgo

et al. 2019

Molecular Nutrition Food Res

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Scope: Extra virgin olive oil (EVOO) is rich in phenolic compounds, including hydroxytyrosol (HTy) and hydroxytyrosyl acetate (HTy-Ac), which have presented multiple beneficial properties. Their impact on inflammatory responses in human keratinocytes and modes of action have not been addressed yet. Methods and results: Primary human keratinocytes are pretreated with HTy-Ac or HTy for 30 min and stimulated with IL-1 or Toll-like receptor 3 ligand (TLR3-l). Thymic stromal lymphopoietin (TSLP), measured by ELISA, is attenuated by both polyphenols in a dose-dependent manner. The expression of several inflammation-related genes, including distinct TSLP isoforms and IL-8, are assessed by quantitative RT-PCR and likewise inhibited by HTy-Ac/HTy. Mechanistically, EVOO phenols counteracts I B degradation and translocation of NF-B to the nucleus, a transcription factor of essential significance to TSLP and IL-8 transcriptional activity; this is evidenced by immunoblotting. Accordingly, NF-B recruitment to critical binding sites in the TSLP and IL-8 promoter is impeded in the presence of HTy-Ac/HTy, as demonstrated by chromatin immunoprecipitation. Promoter reporter assays finally reveal that the neutralizing effect on NF-B induction has functional consequences, resulting in reduced NF-B-directed transcription.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Aparicio‐Soto

Redhu

Sánchéz-Hidalgo

et al. 2019

Molecular Nutrition Food Res

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“…Siddique et al loaded hydrocortisone and hydroxytyrosol—a glucocorticoid for topical application, and an antioxidant molecule, respectively, in chitosan NPs, which were then formulated in an aqueous cream [86]. The authors reported no systemic effects of the drugs nor toxicity, with enhanced safety and tolerability of the developed cream.…”

Section: Nanoparticles For Atopic Dermatitismentioning

confidence: 99%

Trends in Atopic Dermatitis—From Standard Pharmacotherapy to Novel Drug Delivery Systems

Souto

Dias-Ferreira

Oliveira

et al. 2019

IJMS

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Atopic dermatitis (AD) is a predominant and deteriorating chronic inflammation of the skin, categorized by robust burning and eczematous lacerations in diverse portions of the body. AD affects about 20% of both offspring and adults worldwide. The pathophysiology of AD combines environmental, hereditary, and immunological aspects, together with skin barrier dysfunction. The procedures used to prevent the disease are the everyday usage of creams to support the restoration of the epidermal barrier. The classical treatments include the use of topical corticosteroids as a first-line therapy, but also calcineurin inhibitors, antihistamines, antibiotics, phototherapy, and also immunosuppressant drugs in severe cases of AD. Topical drug delivery to deeper skin layers is a difficult task due to the skin anatomic barrier, which limits deeper penetration of drugs. Groundbreaking drug delivery systems, based on nanoparticles (NPs), have received much attention due to their ability to improve solubility, bioavailability, diffusion, targeting to specific types of cells, and limiting the secondary effects of the drugs employed in the treatment of AD. Even so, additional studies are still required to recognize the toxicological characteristics and long-term safety of NPs. This review discusses the current classical pharmacotherapy of AD against new nanoparticle skin delivery systems and their toxicologic risks. a prevalence of atopic conditions, as allergic rhinitis or bronchial asthma, and food allergies [2]. Topical administration of drugs is still the main therapeutic approach for AD. Despite this, several disadvantages may be cited as reduced patient compliance (a consequence of adverse effects as skin irritation or allergy), low efficiency, and specificity of these systems in delivering therapeutic drugs [3]. Innovative drug delivery systems should, therefore, exhibit the capacity to penetrate the stratum corneum (SC), which is naturally impermeable to a range of substances, in order to reduce adverse effects and increase drug targeting [3][4][5]. There is still no medication capable of reversing the pathological effects of AD. However, formulations based on nanoparticles (NPs) have been exploited for topical administration of drugs and are expected to overcome the above-mentioned limitations [6][7][8]. PathophysiologyAD, also called atopic eczema, is the most common skin disease, characterized by a pattern of pruritus, skin deterioration, and chronic inflammation [1,6,7]. This illness affects individuals in early-, mid-or late-stages of their lives and does not have a known cure so far. Over the course of the disease, the levels of IgE increase drastically leading to cutaneous signals that appear in early ages and persist until late stages of life, when they begin to disappear. Because of this, AD is also labelled as "allergic march" [2].AD results from a multiplicity of factors such as environmental injuries, impairments against the natural barrier of the skin and response of the immune system. This latter enhances the ac...

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“…Siddique and coauthors [[39], [40], [41]] exploited nanoparticles for a targeted delivery of systemic corticosteroids at the inflammation site. In a murine model, topically applied cationic polymeric chitosan-based nanoparticles (CSNPs) loaded with anti-inflammatory hydrocortisone and antimicrobial hydroxytyrosol (HC-HT-CSNPs, size of 228.5 ± 7 nm and positive surface charge of 39±5 mV) displayed optimal epidermal and dermal permeation, reaching the deepest skin layers with an efficiency 2.46-fold higher with respect to the commercial reference formulation.…”

Section: Atopic Dermatitis Nanoparticles and Nanocarriersmentioning

confidence: 99%

Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature

Damiani

Eggenhöffner

Pigatto

et al. 2019

Bioactive Materials

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Atopic dermatitis is a chronic, relapsing, non-contiguous, exudative eczema/dermatitis, which represents a complex, multi-factorial disorder, due to an impairment of the stratum corneum barrier. Currently available drugs have a low skin bioavailability and may give rise to severe adverse events. Nanotechnologies, including nano-particles, liposomes, nano-gels, nano-mixtures, nano-emulsions and other nano-carriers, offer unprecedented solutions to these issues, enabling: i) the management of different clinical forms of atopic dermatitis, especially the recalcitrant ones, i) a better bio-availability and trans-dermal drug targeted delivery at the inflammation site, ii) dose control, iii) significant improvements both in clinical symptoms and immune responses, iv) with less adverse events being reported and a better safety profile. However, some nano-sized structures could amplify and even worsen symptoms in particularly susceptible individuals. Furthermore, most studies included in the present systematic review have been conducted in-vitro or in-vivo, with few randomized controlled clinical trials (RCTs). Future investigations should adopt this design in order to enable scholars achieving robust findings and evidence. Therefore, given the above-mentioned shortcomings, further research in the field is urgently warranted.

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Potential treatment of atopic dermatitis: tolerability and safety of cream containing nanoparticles loaded with hydrocortisone and hydroxytyrosol in human subjects

Cited by 46 publications

References 35 publications

Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Olive‐Oil‐Derived Polyphenols Effectively Attenuate Inflammatory Responses of Human Keratinocytes by Interfering with the NF‐κB Pathway

Trends in Atopic Dermatitis—From Standard Pharmacotherapy to Novel Drug Delivery Systems

Nanotechnology meets atopic dermatitis: Current solutions, challenges and future prospects. Insights and implications from a systematic review of the literature

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