Duo photoprotective effect via silica-coated zinc oxide nanoparticles and Vitamin C nanovesicles composites.

OBJECTIVE: Zinc Oxide nanoparticles (ZnO NPs) are used widely in nowadays personal care products, especially sunscreens, as a protector against UV irradiation. Yet, they have some reports of potential toxicity. Silica is widely used to cage ZnO NPs to reduce their potential toxicity. Vitamin C derivative, Magnesium Ascorpyl Phosphate (MAP), is a potent antioxidant that can efficiently protect human skin from harmful impacts of UV irradiation and oxidative stress. The combination of silica coated ZnO NPs and MAP nanovesicles could have potential synergistic protective effect against skin photodamage. METHODS: Silica coated ZnO NPs and MAP nanovesicles (ethosomes and niosomes) were synthesized, formulated, and evaluated as topical gels. These gel formulations were evaluated in mice for their photoprotective effect against UV irradiation through histopathology and immuno-histochemistry study. Split-face clinical study was conducted to compare the effect of application of silica coated ZnO NPs either alone or combined with MAP nanovesicles. Their photoprotective action was evaluated, using Antera 3D® camera, for melanin level, roughness index and wrinkles depth. RESULTS: Silica coated ZnO NPs when combined with MAP nanovesicles protected mice skin from UV irradiation and decreased the expression of the proinflammatory cytokines, NF-κB. Clinically, silica coated ZnO NPs, alone or combined with MAP nanovesicles, could have significant effect to decrease melanin level, roughness index and wrinkles depth with higher effect for the combination. CONCLUSION: A composite of silica coated ZnO NPs and MAP nanovesicles could be a promising cosmetic formulation for skin protection against photodamage signs such as hyperpigmentation, roughness, and wrinkles.

Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation, in-vitro and ex-vivo evaluation, factorial optimization and clinical assessment in melasma patients.

Ascorbic acid (vitamin C) is an antioxidant that is widely used in cosmetics in skincare products. Due to the excessive low stability of ascorbic acid in cosmetic formulations, the stabilized ascorbic acid derivative, magnesium ascorbyl phosphate (MAP) was formulated as vesicular carriers; ethosomes and niosomes. The aim was to deliver MAP at the intended site of action, the skin, for sufficient time with enhanced permeation to get an effective response. Ethosomes were formulated using a full 32 factorial design to study ethanol and phospholipid concentration effect on ethosomes properties. Niosomes were formulated using 23 factorial designs to study the effect of surfactant type, surfactant concentration and cholesterol concentration on niosomes properties. The prepared formulations were evaluated for their Entrapment efficiency, particle size, polydispersity index, zeta potential and % drug permeated. The optimized ethosomal and niosomal formulations were incorporated into carbopol gel and evaluated for their permeation, skin retention and stability. A comparative split-face clinical study was done between the ethosomal and niosomal formulations for melasma treatment using Antera 3 D® camera. The optimized ethosomal and niosomal gels showed comparable controlled permeation and higher skin retention over their ethosomes and niosomes formulations respectively. Magnesium ascorbyl phosphate ethosomal gel showed clinically and statistically significant melanin level decrease after one month while MAP niosomal gel showed clinically and statistically significant melanin level decrease after six months. A combination of MAP ethosomes and niosomes could be promising skincare formulations for melasma and hyperpigmentation short and long-term treatment.

Ascorbic acid derivative-loaded modified aspasomes: formulation, in vitro, ex vivo and clinical evaluation for melasma treatment.

Vitamin C (L-Ascorbic acid) has many favourable effects on the skin such as antioxidant, anti-aging and whitening effects. Its instability and low permeability limit its pharmaceutical use in cosmetic and dermatological products. Instead, Mg ascorbyl phosphate (MAP), an ascorbic acid derivative, has the same effect with higher stability is being used. In this work, a vesicular system, aspasomes, containing MAP was developed and evaluated. Aspasomes are multilayered vesicles formed by amphiphiles molecules, Ascorbyl palmitate (ASP), in combination with cholesterol and charged lipids for drug encapsulation. Here, we investigated the use of lecithin instead of the charged lipid dicetyl phosphate for aspasomes development. Nine formulations were prepared and evaluated for their entrapment efficiency, particle size, polydispersity index (PDI) and zeta potential. Their entrapment efficiency ranged from 33.00 ± 2.27 to 95.18 ± 1.06, while their particle size was from 373.34 ± 60.85 to 464.37 ± 93.46 nm with acceptable PDI (from 0.212 ± 0.068 to 0.351 ± 0.061) and zeta potential (from -37.52 ± 2.42 to -50.36 ± 1.82). Three formulations were selected and evaluated for their drug release, permeation and retention into skin. One formulation was selected to be formulated as aspasomal topical cream and gel. The aspasomal cream was found to have enhanced drug permeation and skin retention over the aspasomal gel as well as the aspasomes formulation. MAP aspasomal cream was evaluated clinically as an effective treatment for melasma against 15% trichloroacetic acid (TCA) and the results recorded that the aspasomal cream showed the greatest degree of improvement regarding the hemi-MASI scores with 35% of patients rating it as excellent treatment. The study showed that MAP aspasomal cream can be considered a novel treatment of melasma which is free of side effects. Its efficacy as a monotherapy is superior to that of chemical peeling using 15% TCA.

Gabapentin-saccharin co-crystals with enhanced physicochemical properties and in vivo absorption formulated as oro-dispersible tablets.

The physicochemical properties and in vivo absorption of a drug can be altered through cocrystallization with a suitable coformer. The aim of this study was to prepare and characterize Gabapentin (Gaba)-saccharine (sacch) sweet cocrystals for improvement of Gaba physicochemical properties, stability and in vivo absorption in addition to masking its taste. The prepared cocrystals were incorporated into oro-dispersible tablets as an attractive dosage form for pediatrics and adults. Gaba-sacch sweet cocrystals were prepared and characterized using FTIR, DSC, XRD and SEM analysis. They enhanced Gaba solubility and particle size distribution. Oro-dispersible tablets of the sweet cocrystals were prepared and evaluated in comparison to tablets prepared by Gaba-sacch physical mixture (PM). The tablets prepared by the cocrystals had lower wetting and disintegration time with enhanced drug release than those prepared with the physical mixture. The optimized formulation was evaluated for Gaba pharmacokinetics in rabbits in comparison to Gaba-sacch PM tablet and Gaba commercial oral capsules. This formulation had enhanced in vivo drug absorption through significant higher Cmax and AUC0-24 with shorter Tmax. The prepared Gaba-sacch sweet cocrystals oro-dispersible tablets, in addition to its enhanced in vitro and in vivo performance, can also enhance patient compliance through its palatable taste and ease of administration.

In-vitro and in-vivo respiratory deposition of a developed metered dose inhaler formulation of an anti-migraine drug.

Enhancement of zolmitriptan bioavailability through development of micronized zolmitriptan pressurized metered dose inhaler (MDI) as an alternative to its traditional drug delivery systems. A reversed phase HPLC method for zolmitriptan determination was developed and evaluated. Micronized zolmitriptan MDI formulations were prepared using two different propellants. The prepared formulations were evaluated for mean shot weight, drug content, and leakage rate in addition to in-vitro deposition using next generation impactor where mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), fine particle dose, fine particle fraction (FPF), emitted dose (ED), and dispersibility were determined. The selected formulation was evaluated for in-vivo bronchial absorption in rats. The physicochemical characters of the prepared formulations were found to be dependent mainly on the vapor pressure of the used propellant. MDI formulation prepared with HFA 134a propellant was found to have the lowest MMAD (3.47 ± 0.65) with GSD of 2.3 ± 0.4. It also had the highest FPF (41.9), ED (89.26 ± 2.35) with dispersibility of 46.9%. This formulation, when applied to rats, resulted in faster Tmax (27 ± 5 min) with higher Cmax (1236 ± 116 ng/mL) and AUC(0-12) (3375 ± 482 ng/mL·h) over the oral tablet. Its relative bioavailability was 72.7% which was 1.25 times higher than the oral tablet relative bioavailability. Zolmitriptan MDI formulation was developed using micronized zolmitriptan powder without further modification or particle engineering. The developed formulation using HFA 134a propellant could be favorable alternative, with enhanced bioavailability, to zolmitriptan oral tablet for acute migraine treatment.

Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion.

Zolmitriptan (ZT) is a well-tolerated drug in migraine treatment suffering from low bioavailability due to low amount of the drug that reaches the brain after oral and nasal delivery. Development of new nasal mucoadhesive nanoemulsion formulation for zolmitriptan may success in delivering the drug directly from the nose to the brain to achieve rapid onset of action and high drug concentration in the brain which is required for treatment of acute migraine. ZT mucoadhesive nanoemulsion were prepared and characterized for drug content, zeta potential, particle size, morphology, residence time and permeation through the nasal mucosa. The selected formula was tested in-vivo in mice for its pharmacokinetics in comparison with intravenous and nasal solution of zolmitriptan. Results showed that addition of chitosan as mucoadhesive agent in 0.3% concentration to the nanoemulsion enhanced its residence time and zetapotential with no significant effect on the globule size. All tested formulations showed higher permeability coefficients than the zolmitriptan solution through the nasal mucosa. In-vivo studies showed that the mucoadhesive nanoemulsion formulation of zolmitriptan has higher AUC0-8 and shorter Tmax in the brain than the intravenous or the nasal solution. This was related to the small globule size and higher permeability of the formulation.