Novel Nanotechnological Strategies for Skin Anti-aging.

BACKGROUND: Nanoparticle formulations development for anti-aging treatment is increasing due to their multifunctional properties. These nanotechnological strategies can target cellular/ molecular pathways of the skin affected by the aging process. However, a review of these strategies is required to discuss their efficacy/safety and establish the needs for further research. OBJECTIVE: Innovative nanotechnological advances for skin anti-aging/rejuvenation are summarized and discussed in this work. METHODS: The information in this review was extracted from recent and relevant studies using nanotechnology for anti-aging treatment from scientific databases. RESULTS AND DISCUSSION: Results show an enhanced skin anti-aging effect of actives-loaded nanoparticles of next generation (nanostructured lipid carriers, fullerenes, transfersomes, protransfersomes, niosomes, ethosomes, transethosomes, glycerosomes, phytosomes) compared with nanocarriers of first generation or conventional formulations. Anti-aging active ingredients such as, flavonoids (rutin, hesperidin, quercetagetine, quercetin, epigallocatechin-3-gallate, myricetin, silibinin, curcuminoids, isoflavones); vitamins (E, D₃, CoQ10); acids (hyaluronic, ascorbic, rosmarinic, gallic); extracts (Citrus sinensis, Tagetes erecta L., Achillea millefolium L., Citrus aurantium L., Glycyrrhiza glabra L., Aloe vera, propolis earned by Apis mellifera); and other compounds (adenosine, beta-glucan, heptapetide DEETGEF, resveratrol, cycloastragenol, melatonin, botulinum toxin, grapeseed oil), have been successfully entrapped into nanoparticles for skin rejuvenation. This encapsulation has improved their solubility, bioavailability, stability, permeability, and effectivity for skin anti-aging, providing a controlled drug release with minimized side effects. CONCLUSION: Recent studies show a trend of anti-aging herbal active ingredients-loaded nanoparticles, enhancing the moisturizing, antioxidant, regenerating and photoprotective activity of the skin. Suitable safety/shelf-life stability of these novel formulations is key to a successful translation to the clinic/industry.

Effects of Process and Formulation Parameters on Submicron Polymeric Particles Produced by a Rapid Emulsion-Diffusion Method.

Emulsification-diffusion method is often used to produce polymeric nanoparticles. However, their numerous and/or lengthy steps make it difficult to use widely. Thus, a modified method using solvent blends (miscible/partially miscible in water, 25-100%) as the organic phases to overcome these disadvantages and its design space were investigated. To further simplify the process, no organic/aqueous phase saturation and no water addition after the emulsification step were performed. Biodegradable (PLGA) or pH-sensitive (Eudragit® E100) nanoparticles were robustly produced using low/medium shear stirring adding dropwise the organic phase into the aqueous phase or vice versa. Several behaviors were also obtained: lowering the partially water-miscible solvent ratio relative to the organic phase or the poloxamer-407 concentration; or increasing the organic phase polarity or the polyvinyl alcohol concentration produced smaller particle sizes/polydispersity. Nanoparticle zeta potential increased as the water-miscible solvent ratio increased. Poloxamer-407 showed better performance to decrease the particle size (~50 nm) at low concentrations (≤1%, w/v) compared with polyvinyl alcohol at 1-5% (w/v), but higher concentrations produced bigger particles/polydispersity (≥600 nm). Most important, an inverse linear correlation to predict the particle size by determining the solubility parameter was found. A rapid method to broadly prepare nanoparticles using straightforward equipment is provided.

Development, Characterization, Optimization, and In Vivo Evaluation of Methacrylic Acid-Ethyl Acrylate Copolymer Nanoparticles Loaded with Glibenclamide in Diabetic Rats for Oral Administration.

The methacrylic acid-ethyl acrylate copolymer nanoparticles were prepared using the solvent displacement method. The independent variables were the drug/polymer ratio, surfactant concentration, Polioxyl 40 hydrogenated castor oil, the added water volume, time, and stirring speed, while size, PDI, zeta potential, and encapsulation efficiency were the response variables analyzed. A design of screening experiments was carried out to subsequently perform the optimization of the nanoparticle preparation process. The optimal formulation was characterized through the dependent variables size, PDI, zeta potential, encapsulation efficiency and drug release profiles. In vivo tests were performed in Wistar rats previously induced with diabetes by administration of streptozotocin. Once hyperglycemia was determined in rats, a suspension of nanoparticles loaded with glibenclamide was administered to them while the other group was administered with tablets of glibenclamide. The optimal nanoparticle formulation obtained a size of 18.98 +/- 9.14 nm with a PDI of 0.37085 +/- 0.014 and a zeta potential of -13.7125 +/- 1.82 mV; the encapsulation efficiency was of 44.5%. The in vivo model demonstrated a significant effect (p < 0.05) between the group administered with nanoparticles loaded with glibenclamide and the group administered with tablets compared to the group of untreated individuals.

Microagujas y Transcutol® como promotores de la penetración transdérmica de sibutramina formulada en parche transdérmico / Microneedles and Transcutol® as transdermal penetration enhancers of sibutramine formulated in a transdermal patch

Introducción: la principal barrera de permeación que tenemos es la piel. A pesar de ser una barrera casi impermeable para la mayoría de sustancias, se han buscado maneras para mejorar su permeabilidad utilizando nuevas tecnologías como es el uso de microagujas o promotores químicos como el Transcutol®. Objetivo: desarrollar y caracterizar un parche transdérmico a base de clorhidrato de sibutramina como fármaco modelo, usando Transcutol® y microagujas como agentes promotores de la penetración transdérmica. Métodos: se realizó la caracterización fisicoquímica de los parches mediante estudios de microscopia con luz polarizada, estudios de bioadhesión y resistencia a la ruptura. Los estudios de difusión se efectuaron en celdas de difusión verticales tipo Franz, utilizando piel abdominal humana como membrana entre ambos compartimentos. La cuantificación del principio activo se realizó mediante electroforesis capilar. Resultados: se obtuvieron parches bioadhesivos, con una adecuada estabilidad del activo en la matriz polimérica de quitosán al no precipitarse. El uso de Transcutol® y microagujas incrementó el paso de clorhidrato de sibutramina a través de piel humana con respecto al parche control. Se obtuvieron valores de flujo de 0,0649 mg.cm-2.h-1 y 0,0816 mg.cm-2.h-1 en el parche con agente promotor y microagujas de 1 y 2 mm respectivamente, en comparación con los valores de flujo de 0,0527 mg.cm-2.h-1 y 0,0554 mg.cm-2.h-1 para el parche sin agente promotor (control) utilizando microagujas de 1 y 2 mm respectivamente. Conclusiones: los resultados ponen de manifiesto la posibilidad de usar Transcutol® y microagujas para incrementar el paso de fármacos potentes y con estructura similar a la sibutramina por vía transdérmica, lo que genera de esta manera nuevas alternativas a las formas farmacéuticas orales para el tratamiento de padecimientos y enfermedades(AU)

Introduction: the main permeation barrier is the skin. Although it is almost an impermeable barrier to most substances, new ways have been examined to improve its permeability by using new technologies such as microneedles and chemical enhancers like Transcutol®. Objective: to develop and to characterize a transdermal patch containing sibutramine hydrochloride as model drug and using microneedles and Transcutol® as transdermal drug delivery enhancers. Methods: Physicochemical characterization of sibutramine hydrochloride patches using polarized light microscopy, bioadhesion, tensile strength studies. The diffusion studies were performed in Franz-type diffusion cells with human abdominal skin as a sort of membrane between both compartments. The active ingredient was quantified through capillary electrophoresis. Results: bioadhesive patches were obtained, with adequate stability of sibutramine hydrochloride in the polymer matrix of chitosan. The use of microneedles and Transcutol® increased sibutramine hydrochloride delivery through the human skin when compared with the control patch. The flow rates were 0.0649 mg.cm-2.h-1 and 0,0816 mg.cm-2.h-1 in the enhanced patch by using 1 and 2 mm microneedles respectively, in comparison with flow rates of 0,0527 mg.cm-2.h-1 and 0.0554 mg.cm-2.h-1 for the control patch having no enhancing agent with 1 and 2 mm microneedles respectively. Conclusions: the results show that it is possible to use Transcutol® and microneedles to increase the delivery of potent drugs having a structure similar to that of sibutramine through transdermal administration. All this generates new alternatives to oral pharmaceuticals in order to treat ailments and diseases(AU)

Targeting nicotine addiction: the possibility of a therapeutic vaccine.

Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA) for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results show that the efficiency of the vaccines is directly related to the antibody levels, a fact which will help to optimize the vaccine effect. The vaccines are expected to appear on the market between 2011 and 2012.

Preparation and characterization of triclosan nanoparticles intended to be used for the treatment of acne.

This work focuses on the preparation and characterization of nanoparticles containing triclosan. Additionally, in vitro percutaneous permeation of triclosan through pig ear skin was performed, and comparisons were made with two commercial formulations: An o/w emulsion and a solution, intended for the treatment of acne. The nanoparticle suspensions were prepared by the emulsification-diffusion by solvent displacement method, using Eudragit® E 100 as polymer. All batches showed a size smaller than 300 nm and a positive Zeta potential, high enough (20-40 mV) to ensure a good physical stability. Differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) studies suggested that triclosan was molecularly dispersed in the nanoparticle batches containing up to 31% of triclosan, with good encapsulation efficiency (95.9%). The results of the in vitro permeation studies showed the following order for the permeability coefficients: Solution>cream≈nanoparticles; while for the amount retained in the skin, the order was as follows: cream>nanoparticles≈solution. Nanoparticles, being free of surfactants or other potentially irritant agents, can be a good option for the delivery of triclosan to the skin, representing a good alternative for the treatment of acne.

The use of sonophoresis in the administration of drugs throughout the skin.

Transdermal drug delivery offers an attractive alternative to the conventional drug delivery methods of oral administration and injection. However, the stratum corneum acts as a barrier that limits the penetration of substances through the skin. Application of ultrasound to the skin increases its permeability (sonophoresis) and enables the delivery of various substances into and through the skin. Ultrasound has been used extensively for medical diagnostics and to a certain extent in medical therapy (physiotherapy, ultrasonic surgery, hyperthermia). Nevertheless, it has only recently become popular as a technique to enhance drug release from drug delivery systems. A number of studies suggest the use of ultrasound as an external mean of delivering drugs at increased rates and at desired times. This review presents the main findings in the field of sonophoresis, namely transdermal drug delivery and transdermal monitoring. Particular attention is paid to proposed enhancement mechanisms and trends in the field of topical and transdermal delivery.