Cutaneous use of lipid nanoparticles (solid lipid nanoparticles, SLN and nanostructured lipid carriers, NLC) has been showing promising results. These systems consist of low viscosity aqueous ...dispersions, being usually employed by means of semi-solid formulations with adequate consistency for skin application.
This review addresses the cutaneous use of lipid nanoparticles for therapeutic and cosmetic applications. Initially, general information related to pharmaceutical semi-solid formulations is presented. Afterwards, the effects of SLN and NLC on the skin, and technological aspects related to semi-solid systems based on SLN or NLC are described. Finally, the most relevant studies related to the formulations based on SLN and NLC, for cosmetic and therapeutic applications, are reported.
Notwithstanding the cutaneous use of SLN and NLC has been proposed for both local and transdermal delivery, the reported studies show promising results only for local application. In this sense, more research is required to better understanding the interaction mechanisms of lipid nanoparticles with skin lipids. Furthermore, the development of standard methods for skin experiments with nanoparticles is necessary.
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Objective
Skin health and beauty are a cornerstone of general well‐being in humans. Anti‐ageing cosmetics are used to provide a healthy and youthful appearance. Among the different cosmetic actives, ...antioxidants are incorporated in anti‐ageing products due to their beneficial effects in preventing and minimizing the signs of skin ageing. This work aims to understand how anti‐ageing formulations changed in the past 7 years regarding pure antioxidants composition.
Methods
Data were collected from anti‐ageing formulations commercialized in main stores and pharmacies in the Portuguese market. The study started on 2011 and was updated with products launched or whose composition has been renewed on 2013, 2015 or 2018.
Results
Ascorbic acid and tocopherol and their derivatives were consistently the most used antioxidants in anti‐ageing formulations; followed by niacinamide and retinyl palmitate. Seven ascorbic acid derivatives are currently used in anti‐ageing formulations while only three tocopherol derivatives were identified in this study. Several combinations of antioxidants were routinely found, mainly tocopherol (or tocopherol derivatives) with other antioxidants and tocopherol with tocopherol derivatives. We have not identified emerging antioxidants with great impact in anti‐ageing formulations even though niacinamide and retinyl palmitate exhibited over 10% more usage in 2018.
Conclusion
This insight is relevant to the cosmetic industry providing a better understanding of the scientific‐based formulation of modern cosmetics and supports the need for innovative antioxidants in anti‐ageing cosmetics.
Résumé
Objectif
La santé de la peau et la beauté constituent la base du bien‐être général chez l'homme. Les cosmétiques anti‐âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents principes actifs des cosmétiques, des antioxydants sont incorporées dans les produits anti‐âge en raison de leur effet bénéfique sur la prévention et la réduction des signes de vieillissement de la peau. Ce travail vise à comprendre comment les formulations anti‐âge ont évolué au cours des 7 dernières années au niveau des antioxydants purs composition.
Méthodes
Les données ont été recueillies sur des formulations anti‐âge commercialisées dans les principaux magasins et pharmacies du marché portugais. Cette étude a commencé en 2011 et a été mise à jour avec des produits mis sur le marché ou dont la composition a été renouvelée en 2013, 2015 ou 2018.
Résultats
L'acide ascorbique et tocophérol et leurs dérivés sont systématiquement les antioxydants les plus utilisés dans les formulations anti‐âge; ils sont suivis de la niacinamide et du palmitate de rétinol. Sept dérivés d'acide ascorbique sont actuellement utilisés pour lutter contre le vieillissement, tandis que seulement trois dérivés de tocophérol ont été identifiés dans cette étude. Plusieurs combinaisons d'antioxydants ont été systématiquement observées, principalement le tocophérol ou les dérivés de tocophérol avec d'autres antioxydants, et le tocophérol avec des dérivés de tocophérol. Nous n'avons pas identifié de nouveaux antioxydants présentant un impact majeur dans les formulations anti‐âge, même si la niacinamide et le palmitate de rétinol ont vu leur utilisation augmenter de 10% en 2018.
Conclusion
Cette perspective est pertinente pour le secteur des cosmétiques. Elle permet de mieux comprendre la formulation scientifique des cosmétiques modernes et confirme le besoin d'innover au niveau des antioxydants utilisés dans les produits anti‐âge. Les cosmétiques anti‐âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents actifs cosmétiques, les antioxydants sont incorporés dans les produits anti‐âge en raison de leurs effets bénéfiques dans la prévention et la réduction des signes du vieillissement cutané. Ce travail vise à comprendre comment les formulations anti – vieillissement ont changé au cours des 7 dernières années en ce qui concerne la composition en antioxydants purs.
Anti‐ageing cosmetics are used to provide a healthy and youthful appearance. Among the different cosmetic actives, antioxidants are incorporated in anti‐ageing products because of their beneficial effects in preventing and minimizing the signs of skin ageing. This work aims to understand how anti‐ageing formulations changed in the past 7 years regarding pure antioxidants composition.
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•The effect of 3 antioxidants in the photostabilization of avobenzone were studied.•The most effective antioxidant in sunscreen preparations was ubiquinone.•Antioxidants may be used ...to enhance UV-filter stability.
Avobenzone is one of the most common UVA-filters in sunscreens, and is known to be photounstable. Some of the strategies used to stabilize this filter present some drawbacks like photosensitization reactions. Antioxidants are widely used as cosmetic ingredients that prevent photoageing and complement the photoprotection offered by the UV-filters preventing or reducing photogenerated reactive species. The purpose of this work was to study the effect of antioxidants in the photostabilization of avobenzone. The filter dissolved in dimethyl sulfoxide or incorporated in a sunscreen formulation was irradiated with simulated solar radiation (750W/m2). The tested antioxidants were vitamin C, vitamin E, and ubiquinone. The area under the curve of the absorption spectrum for UVA range and the sun protection factor (SPF) were calculated. Vitamin E (1:2), vitamin C (1:0.5) and ubiquinone (1:0.5) were the more effective concentrations increasing the photostability of avobenzone. In sunscreen formulations, the most effective photostabilizer was ubiquinone which also promoted an increase in SPF.
This knowledge is important to improve effectiveness of sunscreen formulation. Antioxidants can be valuable ingredients for sunscreens with a triple activity of filter stabilization, SPF boosting and photoageing prevention.
Studies on the development of drug delivery systems have increased because these systems have particular characteristics that allow them to improve therapeutics. Among these, lipid nanoparticles ...(solid lipid nanoparticles, SLNs; and nanostructured lipid carriers, NLCs) have demonstrated suitability for drug targeting. The nasal administration of drug-loaded lipid nanoparticles showed effectiveness in treating central nervous system (CNS) disorders, particularly neurodegenerative diseases, because the nasal route (also called intranasal route) allows direct nose-to-brain drug delivery by means of lipid nanoparticles. Nonetheless, the feasibility of this application remains an open field for researchers. Drawbacks must be overcome before reaching the clinic (e.g., drug absorption at subtherapeutic levels, rapid mucociliary clearance). The intranasal administration of drugs for systemic absorption is effective for treating other conditions, such as cardiovascular diseases, infections, severe pain, and menopausal syndrome. In the near future, it is expected that patients will benefit from the advantages of lipid nanoparticle-based formulations, via the nasal/intranasal route, which bypasses the blood-brain barrier (BBB), avoiding first-pass metabolism and gastrointestinal degradation. This review discusses the use of SLNs and NLCs for nasal drug administration. A brief description of the nasal route and the features of SLNs and NLCs is initially provided.
The nose-to-brain route has been widely investigated to improve drug targeting to the central nervous system (CNS), where lipid nanoparticles (solid lipid nanoparticles - SLN and nanostructured lipid ...carriers - NLC) seem promising, although they should meet specific criteria of particle size (PS) <200 nm, polydispersity index (PDI) <0.3, zeta potential (ZP) ~|20| mV and encapsulation efficiency (EE) >80%. To optimize SLN and NLC formulations, design of experiment (DoE) has been recommended as a quality by design (QbD) tool.
This review presents recently published work on the optimization of SLN and NLC formulations for nose-to-brain drug delivery. The impact of different factors (or independent variables) on responses (or dependent variables) is critically analyzed.
Different DoEs have been used to optimize SLN and NLC formulations for nose-brain drug delivery, and the independent variables lipid and surfactant concentration and sonication time had the greatest impact on the dependent variables PS, EE, and PDI. Exploring different DoE approaches is important to gain a deeper understanding of the factors that affect successful optimization of SLN and NLC and to facilitate future work improving machine learning techniques.
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The main limitation to the success of central nervous system (CNS) therapies lies in the difficulty for drugs to cross the blood–brain barrier (BBB) and reach the brain. Regarding its ...structure and enzymatic complexity, crossing the BBB is a challenge, although several alternatives have been identified. For instance, the use of drugs encapsulated in lipid nanoparticles has been described as one of the most efficient approaches to bypass the BBB, as they allow the passage of drugs through this barrier, improving brain bioavailability. In particular, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been a focus of research related to drug delivery to the brain. These systems provide protection of lipophilic drugs, improved delivery and bioavailability, having a major impact on treatments outcomes. In addition, the use of lipid nanoparticles administered via routes that transport drugs directly into the brain seems a promising solution to avoid the difficulties in crossing the BBB. For instance, the nose-to-brain route has gained considerable interest, as it has shown efficacy in 3D human nasal models and in animal models.
This review addresses the state of the art on the use of lipid nanoparticles to modify the pharmacokinetics of drugs employed in the management of neurological disorders. A description of the structural components of the BBB, the role of the neurovascular unit and limitations for drugs to entry into the CNS is first addressed, along with the developments to increase drug delivery to the brain, with a special focus on lipid nanoparticles. In addition, the obstacle of BBB complexity in the creation of new effective drugs for the treatment of the most prevalent neurological disorders is also addressed. Finally, the proposed strategies for lipid nanoparticles to reach the CNS, crossing or circumventing the BBB, are described. Although promising results have been reported, especially with the nose-to-brain route, they are still ongoing to assess its real efficacy in vivo in the management of neurological disorders.
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Several active compounds are sensitive to light, especially to the ultraviolet radiation (UV-R) leading to their degradation or modification, with lost or decrease of their biological ...activity. The aim of this study was to perform a systematic review regarding photostabilization strategies used on health products and perform a critical appraisal of their effectiveness.
The bibliographic search identified 2261 results and merely 40 studies met the selection criteria. Of these, 85% referred to encapsulation strategies, 10% to antioxidants and 5% to the use of solar filters. Cyclodextrins (CD’s) were the most used encapsulation systems (32.5%) followed by liposomes and lipid nanoparticles (each 17.5%), microparticles (15%) and polymeric nanoparticles (10%). The most effective were found to be liposomes and lipid nanoparticles. However, the different methodological conditions used limit the true relevance of this finding.
A gold standard strategy suitable for all compounds cannot be proposed. Instead, case-by-case evaluation, supported on the photodegradation mechanism is recommended. Systematic studies that compare different photostabilization strategies undertaken with the same irradiation conditions are also needed.
Modeling and comparison of dissolution profiles Costa, Paulo; Sousa Lobo, José Manuel
European Journal of Pharmaceutical Sciences,
05/2001, Letnik:
13, Številka:
2
Book Review, Journal Article
Recenzirano
Over recent years, drug release/dissolution from solid pharmaceutical dosage forms has been the subject of intense and profitable scientific developments. Whenever a new solid dosage form is ...developed or produced, it is necessary to ensure that drug dissolution occurs in an appropriate manner. The pharmaceutical industry and the registration authorities do focus, nowadays, on drug dissolution studies. The quantitative analysis of the values obtained in dissolution/release tests is easier when mathematical formulas that express the dissolution results as a function of some of the dosage forms characteristics are used. In some cases, these mathematic models are derived from the theoretical analysis of the occurring process. In most of the cases the theoretical concept does not exist and some empirical equations have proved to be more appropriate. Drug dissolution from solid dosage forms has been described by kinetic models in which the dissolved amount of drug (
Q) is a function of the test time,
t or
Q=
f(
t). Some analytical definitions of the
Q(
t) function are commonly used, such as zero order, first order, Hixson–Crowell, Weibull, Higuchi, Baker–Lonsdale, Korsmeyer–Peppas and Hopfenberg models. Other release parameters, such as dissolution time (
t
x%
), assay time (
t
x min
), dissolution efficacy (ED), difference factor (
f
1), similarity factor (
f
2) and Rescigno index (
ξ
1 and
ξ
2) can be used to characterize drug dissolution/release profiles.
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Diazepam is commonly used in the management of epileptic seizures, although it has limitations that can be overcome by using formulations that are easier to administer and capable of ...directing the drug to the brain. In this field, it has been reported that the use of nanostructured lipid carriers (NLC) via intranasal (or via nose-to-brain) promotes the targeting of drugs to the brain, improving the effectiveness of therapy.
The aim of this work was to optimize two diazepam-loaded NLC formulations for nose-to-brain delivery, one with positive surface charge and one with negative surface charge. The quality by design (QbD) approach was used to design the experiments, where the quality target product profile (QTPP), the risk assessment and the critical quality attributes (CQAs) were defined to ensure safety, efficacy and quality of the final formulations.
The experiments started with the optimization of critical material attributes (CMAs), related to the ratios of lipids and emulsifiers, followed by the selection of critical process parameters (CPPs), related to the production methods of the diazepam-loaded NLC formulation (ultrasound technique and high-pressure homogenization - HPH). Afterwards, the positive surface charge of the diazepam-loaded NLC was optimized. Finally, the biocompatibility with human neuronal cells of the formulation with a negative surface charge and of the formulation with a positive surface charge was evaluated.
The results of the optimization of the CMAs showed that the ratios of lipids and emulsifiers more adequate were 6.7:2.9 and 4.2:0.3 (% w,w), respectively. Regarding the CPPs, HPH was considered the most suitable production method, resulting in an optimized diazepam-loaded NLC formulation (F1C15) with negative surface charge, showing particle size of 69.59 ± 0.22 nm, polydispersity index (PDI) of 0.19 ± 0.00, zeta potential (ZP) of −23.50 ± 0.24 mV and encapsulation efficiency (EE) of 96.60 ± 0.03 %. The optimized diazepam-loaded NLC formulation (F2A8) with positive surface charge had particle size of 124.40 ± 0.84 nm, PDI of 0.17 ± 0.01, ZP of 32.60 ± 1.13 mV and EE of 95.76 ± 0.24 %. In addition, the incorporation of diazepam in NLC resulted in a sustained release of the drug. No significant changes in particle size, PDI, ZP and EE were observed for the formulation F1C15, after 3 months of storage, whereas for formulation F2A8, particle size increased significantly. Biocompatibility studies showed that the formulation F2A8 was more cytotoxic than the formulation F1C15. Thereby, we conclude that the formulation F1C15 is more suitable for targeting the brain, when compared with the formulation F2A8.
From the results of these studies, it can be confirmed that the QbD approach is an adequate and central tool to optimize NLC formulations.
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•Nanostructured lipid carriers (NLC) and nanoemulsions (NE) are safe for skin use.•Vitamin E-loaded NLC and NE demonstrate in vivo hydration potential.•Hydrogels containing NLC ...exhibited good skin occlusive properties.•Hydrogels containing NE performed a fast skin hydration effect.
Lipid-based nanosystems, such as nanostructured lipid carriers (NLC) and nanoemulsions (NE) have been described as promising alternatives to conventional formulations for increase skin hydration. Besides, these systems have been used as efficient vehicles for lipophilic molecules that improve skin properties (e.g. vitamin E).
In this study, we performed comparative investigations between hydrogels formulations containing vitamin E-loaded NLC (HG-NLCVE) and vitamin E-loaded nanoemulsion (HG-NEVE). The experiments started with particle size measurements, which showed no significant differences between nanoparticles/nanodroplets sizes after incorporation in the hydrogel net (386 nm vs. 397 nm for HG-NLCVE and 402 nm vs. 514 nm for HG-NEVE). Afterwards, in vitro biocompatibility studies in human keratinocytes were carried out, being observed that the lipid-based nanosystems were more cytotoxic for the cells before incorporation in the hydrogel. Finally, the formulations hydration potential and sensory attributes for skin application were evaluated by in vitro occlusion tests and in vivo human experiments. The results showed that the HG-NLCVE exhibited the best occlusive properties, whereas the HG-NEVE performed a faster skin hydration effect. Furthermore, the latter was selected as the most attractive for skin application, although the HG-NLCVE was described as more suitable to obtain a long-lasting effect. This study demonstrated the in vitro and in vivo safety and hydration potential of hydrogels containing vitamin E-loaded lipid-based nanosystems. These results establish a basis to assess the cutaneous use of these systems, despite more in vivo experiments, for longer periods and in more volunteers, are required before commercialization.
