An evaluation of tocotrienol ethosomes for transdermal delivery using Strat-M ® membrane and excised human skin

Rajesh Sreedharan Nair, Nashiru Billa, Chee-Onn Leong, Andrew P Morris

Pharm Dev Technol . 2021 Feb;26(2):243-251. doi: 10.1080/10837450.2020.1860087. Epub 2020 Dec 15.

Abstract

Tocotrienol (TRF) ethosomes were developed and evaluated in vitro for potential transdermal delivery against melanoma. The optimised TRF ethosomal size ranged between 64.9 ± 2.2 nm to 79.6 ± 3.9 nm and zeta potential (ZP) between -53.3 mV to -62.0 ± 2.6 mV. Characterisation of the ethosomes by ATR-FTIR indicated the successful formation of TRF-ethosomes. Scanning electron microscopy (SEM) images demonstrated the spherical shape of ethosomes, and the entrapment efficiencies of all the formulations were above 66%. In vitro permeation studies using full-thickness human skin showed that the permeation of gamma-T3 from the TRF ethosomal formulations was significantly higher (p < 0.05) than from the control. The cumulative amount of gamma-T3 permeated from TRF ethosome after 48 hours was 1.03 ± 0.24 µg cm-2 with a flux of 0.03 ± 0.01 µg cm-2 h-1. Furthermore, the flux of gamma-T3 across the Strat-M ® and the epidermal membrane was significantly higher than that across full-thickness human skin (p < 0.05). In vitro cytotoxicity studies on HaCat cells showed significantly higher cell viability than the pure drug solution (p < 0.05). The enhanced skin permeation and high cell viability associated with this formulation suggest a promising carrier for transdermal delivery.

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Advancing skin delivery of α-tocopherol and γ-tocotrienol for dermatitis treatment via nanotechnology and microwave technology

Mohd Saufi Harun, Tin Wui Wong, Chee Wai Fong

Int J Pharm . 2021 Jan 25;593:120099. doi: 10.1016/j.ijpharm.2020.120099. Epub 2020 Nov 28.

Abstract

This study investigated combination nanocarrier and microwave system for α-tocopherol and γ-tocotrienol delivery against dermatitis, without skin thinning effect of steroids. The vitamin E was formulated into water-rich/water-poor nanoemulsions, and had their droplet size, zeta potential, morphology, therapeutic content, encapsulation efficiency and release, in vitro skin therapeutics/nanoemulsion penetration, retention and permeation profiles, and in vivo pharmacodynamics characteristics examined, with skin pre-treated by precision microwave when applicable. The nanoemulsions had droplet sizes <150 nm and negative zeta potential values. The skin pre-treatment by microwave (1 mW/3985 MHz) promoted therapeutics accumulation in epidermis through enhancing nanoemulsion penetration into skin. The combination nano- and microwave technologies fluidized skin lipid and protein domains with epidermal microstructures being fluidized to a greater extent than dermis, allowing a relatively high epidermal-to-dermal nanoemulsion distribution. Microwave of lower or higher than 3985 MHz brought about lower skin therapeutics/nanoemulsion accumulation due to insufficient lipid/protein domain fluidization or microwave-skin interaction limiting at skin surfaces only. Using water-rich nanoemulsion with higher therapeutic release and skin pre-treatment with 3985 MHz microwave, dermatitis was alleviated in vivo without skin thinning of standard steroid. The use of combination microwave and nanotechnology promotes vitamin delivery and translates to positive dermatitis treatment outcome that warrants future investigation.

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Epidermal Growth Factor and Tocotrienol-Rich Fraction Cream Formulation Accelerates Burn Healing Process Based on Its Gene Expression Pattern in Deep Partial-Thickness Burn Wound Model

Hui-Fang Guo, Razana Mohd Ali, Roslida Abd Hamid, Sui Kiat Chang, Mohammed Habibur Rahman, Zaida Zainal, Huzwah Khaza'ai

Int J Low Extrem Wounds . 2020 Nov 26;1534734620971066. doi: 10.1177/1534734620971066. Online ahead of print.

Abstract

Our previous study has demonstrated that epidermal growth factor (EGF) with tocotrienol-rich fraction (TRF) cream formulation accelerating postburn wound healing with deep partial-thickness burn in rats. Current study was conducted to determine the gene expression levels related to burn wound healing process. A total of 180 Sprague-Dawley rats were randomly divided into 6 groups: untreated control, treated with Silverdin cream, base cream, base cream with 0.00075% EGF, base cream with 3% TRF or base cream with 0.00075% EGF, and 3% TRF, respectively. Burn wounds were created and the above-mentioned creams were applied once daily. Six animals from each group were sacrificed on days 3, 7, 11, 14, and 21 postburn. RNA was extracted from wound tissues and quantitative real-time polymerase chain reaction was performed to analyze the 9 wound healing-related genes against time postburn. Results demonstrated that topically applied EGF + TRF formulation downregulated the expression levels of IL-6 (interluekin-6), TNF-α (tumor necrosis factor-α) and iNOS (inducible nitric oxide synthase) throughout the whole healing process. TGF-β1 (transforming growth factor-β) and VEGF-A (vascular endothelial growth factor-A) were reduced on day 14 postburn. On the contrary, increased expression of Collagen-1 in the early stage of wound healing was observed with no effects on epidemal growth factor receptor (EGFR). The results showed beneficial application of EGF + TRF cream in the treatment of burn wound since it accelerated wound healing by relieving oxidative stress, decreasing inflammation, and promoting proper tissue modelling in the burn wound.

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Vitamin E attenuates the development of bleomycin-induced skin fibrosis in mice

Liang Ruan, Peng Yang, Shuang-Ping Chen, Changhao Wu, Qi-Xing Zhu

Australas J Dermatol . 2020 Oct 30. doi: 10.1111/ajd.13492. Online ahead of print.

Research Letter

Systemic sclerosis, is a progressive connective tissue disease characterised by extensive fibrosis and affects skin as well as various internal organs.1 Skin fibrosis, a highly recognised feature of systemic sclerosis, causes significant physical disability and psychological disorder but is difficult to treat.2 Recently, vitamin E, a natural antioxidant, has been demonstrated to exert anti-fibrotic properties in vitro and in some fibrotic diseases.3-5 This study aimed to investigate the effects of vitamin E on skin fibrosis in bleomycin-induced mouse model of scleroderma and to clarify the underlying mechanisms.

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Vitamin E in Atopic Dermatitis: From Preclinical to Clinical Studies

Cheryl Wei Ling Teo, Shawn Han Yueh Tay, Hong Liang Tey, Yee Wei Ung, Wei Ney Yap

Dermatology . 2020 Oct 16;1-12. doi: 10.1159/000510653. Online ahead of print.

Abstract

Background: Oxidative stress and inflammation are some of the proposed mechanisms involved in the pathogenesis of atopic dermatitis (AD). Current pharmacotherapeutic approaches are effective yet they are not without adverse effects. Vitamin E has great potential as an adjunctive treatment for AD owing to its antioxidant and anti-inflammatory bioactivities.

Summary: This review article summarizes the current available evidence from cellular, animal and clinical studies on the relationship between vitamin E and AD. The future prospects of vitamin E are also discussed. Vitamin E in practice does not show any toxicity to humans within a range of reasonable dosage. Albeit rarely, vitamin E as a contact allergen should be considered. Collectively, this review envisaged vitamin E as an adjunctive treatment for AD patients. Future research on the distinct effects of different vitamin E isoforms as well as their delivery system in skin disorders is needed.

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Isotretinoin and α-tocopherol acetate-loaded solid lipid nanoparticle topical gel for the treatment of acne

Shivani Gupta, Sarika Wairkar, Lokesh Kumar Bhatt

J Microencapsul . 2020 Sep 24;1-9. doi: 10.1080/02652048.2020.1823499. Online ahead of print.

Abstract

Aims: This study was aimed to develop Isotretinoin (ITN) and α-tocopherol acetate (α-TA) loaded solid lipid nanoparticle topical gel for better skin sensitivity and potentiation of efficacy.

Methods: ITN and α-TA-loaded solid lipid nanoparticles (AE-SLN) were prepared by microemulsion method with glyceryl mono-stearate as lipid and tween 80: butanol as surfactantmix and characterised. AE-SLN gel was evaluated for physicochemical characteristics, drug release, skin irritation and anti-acne activity in rats.

Results: AE-SLNs had mean particle size of 193.4 nm (zeta-potential -29 mV) and entrapment efficiency of 84%w/w for ITN and 77.4%w/w for α-TA. AE-SLN gel showed sustained drug release for 24 h with a final cumulative release of 95.8% w/w and 89.1%w/w for ITN and α-TA. AE-SLN gel showed no erythema or edoema in rabbits and potent efficacy in rat model of acne.

Conclusion: In conclusion, AE-SLN gel has the potential to use as a non-irritant topical formulation for the treatment of acne.

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The Efficacy of Amniotic Membrane Stem Cell (AMSC) Metabolite Product and Vitamin E for Wrinkles, Spots, and Pores in Photoaging

Rahmadewi Rahmadewi, Retha Retha, Dyah Ayu Pitasari, Vidyani Adiningtyas Kusumastanto, Agatha Anindita Ayu Ardhaninggar, Irmadita Citrashanty, Maylita Sari, Menul Ayu Umborowati, Cita Rosita Sigit Prakoeswa

Dermatol Res Pract . 2020 Aug 26;2020:1584541. doi: 10.1155/2020/1584541. eCollection 2020.

Abstract

Background: It is expected that a combination of amniotic membrane stem cell metabolite product (AMSC-MP) and vitamin E after fractional CO2 laser as laser-assisted drug delivery (LADD) will provide better effects in photoaging treatment as the combination reaches the target. This promises an option for photoaging therapy in the future.

Materials and methods: Sixty women with photoaged skins were involved in this experimental study. They were then divided into two groups. The treatment group received a topical combination of AMSC-MP and vitamin E, and the control group received AMSC-MP alone after fractional CO2 laser. The treatment was repeated three times.

Result: The Janus assessment results showed a significant difference in pores in the third observation, and the average pore improvements in the treatment group were better than the control group. Wrinkle, UV spot, and polar spot did not show any significant difference.

Conclusion: A combination of the amniotic membrane stem cell metabolite product (AMSC-MP) and vitamin E after fractional CO2 laser as LADD only improves pores in photoaged skins.

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Summary and evidence grading of over-the-counter scar treatments

Konstantin V Grigoryan, Jeremy T Kampp

Int J Dermatol . 2020 Jul 20. doi: 10.1111/ijd.15060. Online ahead of print.

Abstract

Background: Many products claiming to improve scar appearance are readily available on the Internet. Data behind these claims are often difficult to find or summarize. Patients often ask their surgeon for advice for scarring postdermatologic surgery.

Objective: We aim to review the evidence behind several advertised products and techniques that claim to improve postsurgical scarring.

Methods: A PubMed search was performed using products and methods claiming to improve scar appearance along with the terms “scar” and “scarring”.

Results: Published literature on scar massage, taping of scars, silicone gel and sheeting, onion-based extract products, and vitamin E was reviewed. Silicone gel/sheeting as well as taping have the most evidence to help improve scarring, but even then the evidence is conflicting and weak.

Conclusion: Online advertising may tempt patients to buy and trial products to help minimize scarring, although the evidence for the effectiveness of these products is absent to minimal. Dermatologists must be aware of these products to maintain effective patient counseling.

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Suppression of Menthyl Anthranilate (UV-A Sunscreen)-Sensitized Singlet Oxygen Generation by Trolox and α-tocopherol

Shogo Kitasaka, Mikio Yagi, Azusa Kikuchi

Photochem Photobiol Sci . 2020 Jun 2. doi: 10.1039/d0pp00023j. Online ahead of print.

Abstract

Menthyl anthranilate (MA, tradename meradimate) is a UV-A absorber. The interactions of ground-state molecular oxygen with the long-lived triplet state of MA produce singlet oxygen through energy transfer. The quantum yield of singlet oxygen generation is 0.12 in air-saturated ethanol. Kinetic traces of the near-IR phosphorescence of singlet oxygen generated by MA-photosensitization have been measured in the absence and presence of Trolox (a water-soluble analogue of vitamin E and a quencher of singlet oxygen) and α-tocopherol (vitamin E, a natural antioxidant) in ethanol. Fluorescence and transient absorption measurements suggest that Trolox and α-tocopherol quench the lowest excited singlet and triplet states of MA. As a result, Trolox and α-tocopherol suppress MA-photosensitized singlet oxygen generation. Not only the quenching of singlet oxygen but also the suppression of singlet oxygen generation is the mechanism of antioxidant properties of Trolox and α-tocopherol for MA. The ability of α-tocopherol to suppress the MA-photosensitized singlet oxygen generation in isododecane, used as a solvent for an oil-soluble UV absorber, is close to that in ethanol. Suppression of sunscreen-photosensitized singlet oxygen generation is an important method for the formulation of safe cosmetic sunscreens.

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Feasibility of Using Vitamin E-Loaded Poly(ε-caprolactone)/Gelatin Nanofibrous Mat to Prevent Oxidative Stress in Skin

Kalantary S, Golbabaei F, Latifi M, Shokrgozar MA, Yaseri M

J Nanosci Nanotechnol. 2020 Jun 1;20(6):3554-3562. doi: 10.1166/jnn.2020.17486.

Abstract

Some occupational skin exposures lead to the formation of reactive oxygen species (ROS). The occupational exposure of workers to ROS has been found to be associated with an increased risk of developing skin injuries; therefore, it is essential to protect skin against ROS formation. Recently, some studies have been conducted on introducing better alternatives for skin protection. Nanofibers are good candidates for this purpose. The current study was carried out to assess vitamin E-loaded hybrid Poly(ε-caprolactone) (PCL)/gelatin (Gt) nanofibres mats as protective layers of skin exposed to occupational exposures. Vitamin E (VE) was successfully incorporated into PCL/Gt nanofibers while they were formed by electrospinning method. Nanofibers mats were characterized using scanning electron microscopy (SEM) and fourier transform infrared spectroscopy (FTIR). Their degradation behavior, in vitro release, biocompatibility, and antioxidant activity were studied. The diameters of the PCL/Gt/VE nanofibers decreased with the addition of vitamin E. The degradation rate of nanofibers was equal to 42.98 and 50.69% during 7 and 14 days, respectively. Nanofibers containing vitamin E showed an initial burst followed by a sustained release. The PCL/Gt/VE nanofibers exhibited good free radical scavenging activities despite being exposed to a high electrical potential during electrospinning. PCL/Gt/VE nanofibers supported a higher level of viability compared to PCL/Gt ones and significantly assisted human skin cells against tert-Butyl hydroperoxide (t-BHP) induced oxidative stress. Overall, PCL/Gt/VE nanofibers can potentially be used to protect skin against oxidative stress as a novel approach for worker’s healthcare.

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