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1.
Int J Pharm ; 642: 123106, 2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37279867

RESUMO

Topical administration of active substances may be promoted by optimizing not only the vehicle formulation but also the application protocol. The formulation aspects are widely studied in the literature while a few works are dedicated to the development of application methods. In this context, we studied an application protocol usable as a part of skincare routine by investigating the effect of massage on the skin penetration of retinol. Retinol is a lipophilic molecule widely used as an anti-ageing firming agent in cosmetic formulations. Massage was applied to pig skin explants mounted to Franz diffusion cells after or before the deposit of the retinol-loaded formulation. Thetype of skin massage (roll or rotary type) and its duration were varied.The massage protocol had a significant influence on retinol skin penetration. Due to its highly lipophilic character, retinol accumulated into the stratum corneum but, depending on the massage protocol, a significant retinol concentration was obtained after 4 h in epidermis and dermis layers. Results showed that the roll-type massage was significantly more efficient than the rotary process that exhibited little effect on retinol cutaneous penetration. Such results could be interesting for the development of massage devices in association with cosmetic formulations.


Assuntos
Cosméticos , Vitamina A , Animais , Suínos , Vitamina A/metabolismo , Vitamina A/farmacologia , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Cosméticos/metabolismo , Massagem
2.
Soft Matter ; 19(25): 4780-4793, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37318280

RESUMO

For addressing health issues and ecological concerns, the cosmetic and pharmaceutical industries are facing the challenge of designing emulsions without the use of surfactants. Emulsions stabilized by colloidal particles, known as Pickering emulsions, are promising in this matter. In this article, three different types of particles (neutral, anionic and cationic) are used alone or in binary mixtures as stabilizers of Pickering emulsions. The influence of the particles' charge on the emulsions' properties and the synergies between the different types of particles are studied. It is demonstrated that the kinetics of adsorption of the particles at the water/oil interface control the coverage and their organization at the droplet surface, rather than their interactions after adsorption. Binary mixtures of differently charged particles are a powerful way to control the droplet coverage and the particle loading in the emulsions. In particular, the combination of anionic and cationic particles led to smaller droplets and higher particle coverage of emulsion droplets.

3.
Int J Pharm ; 638: 122897, 2023 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-37003313

RESUMO

The influence of hydrophilic surfactants acting on the membrane elasticity of liposomes on the skin absorption of vitamin C is investigated. The purpose of encapsulation inside cationic liposomes is to improve the skin delivery of vitamin C. The properties of elastic liposomes (ELs) are compared to that of conventional liposomes (CLs). ELs are formed by the addition of the "edge activator" Polysorbate 80 to the CLs composed of soybean lecithin, cationic lipid DOTAP (1,2-dioleoyl-3-trimethylammoniopropane chloride), and cholesterol. The liposomes are characterized by dynamic light scattering and electron microscopy. No toxicity is detected in human keratinocyte cells. Evidences of Polysorbate 80 incorporation into liposome bilayers and of the higher flexibility of ELs are given by isothermal titration calorimetry and pore edge tension measurements in giant unilamellar vesicles. The presence of a positive charge in the liposomal membrane increases the encapsulation efficacy by approximately 30% for both CLs and ELs. Skin absorption of vitamin C from CLs, ELs and a control aqueous solution measured in Franz cells shows a high delivery of vitamin C into each skin layer and the acceptor fluid from both liposome types. These results suggest that another mechanism drives skin diffusion, involving interactions between cationic lipids and vitamin C depending on the skin pH.


Assuntos
Lipossomos , Absorção Cutânea , Humanos , Lipossomos/química , Ácido Ascórbico , Polissorbatos , Administração Cutânea , Lipossomas Unilamelares , Vitaminas
4.
J Biol Eng ; 17(1): 31, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095522

RESUMO

BACKGROUND: To produce viral vaccines, avian cell lines are interesting alternatives to replace the egg-derived processes for viruses that do not grow well on mammalian cells. The avian suspension cell line DuckCelt®-T17 was previously studied and investigated to produce a live attenuated metapneumovirus (hMPV)/respiratory syncytial virus (RSV) and influenza virus vaccines. However, a better understanding of its culture process is necessary for an efficient production of viral particles in bioreactors. RESULTS: The growth and metabolic requirements of the avian cell line DuckCelt®-T17 were investigated to improve its cultivation parameters. Several nutrient supplementation strategies were studied in shake flasks highlighting the interest of (i) replacing L-glutamine by glutamax as main nutrient or (ii) adding these two nutrients in the serum-free growth medium in a fed-batch strategy. The scale-up in a 3 L bioreactor was successful for these types of strategies confirming their efficiencies in improving the cells' growth and viability. Moreover, a perfusion feasibility test allowed to achieve up to ~ 3 times the maximum number of viable cells obtained with the batch or fed-batch strategies. Finally, a strong oxygen supply - 50% dO2 - had a deleterious effect on DuckCelt®-T17 viability, certainly because of the greater hydrodynamic stress imposed. CONCLUSIONS: The culture process using glutamax supplementation with a batch or a fed-batch strategy was successfully scaled-up to 3 L bioreactor. In addition, perfusion appeared as a very promising culture process for subsequent continuous virus harvesting.

5.
Int J Pharm ; 630: 122425, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36436744

RESUMO

Nifedipine (NIF) is a Class II drug of the Biopharmaceutical Classification System (BCS) with low oral bioavailability, low dissolution rate and significant hepatic drug metabolism. The transdermal route using supersaturated systems could be considered. For this purpose, physicochemical properties of NIF such as its dissolution rate, may be a limiting factor and must be improved. Crystallization processes assisted by supercritical carbon dioxide (scCO2) and particularly the Rapid Expansion of Supercritical Solution (RESS) process may improve drug bioavailability by reducing particle size and consequently increasing surface area. This study addresses the reduction of NIF particle size using scCO2-RESS as crystallization process. Experimental solubility studies were performed at different temperature (308 and 318 K) and pressure ranges (9-24 MPa). Solubility data were correlated with two thermodynamic models in order to predict NIF solubility in scCO2. Optimized operating conditions, identified by thermodynamic modelling, allowed the production of thinner NIF particles and a size reduction up to ten fold. Particle size reduction improved NIF dissolution kinetics in aqueous medium: after 90 min, 42 % of raw NIF was released against 80 % for crystallized NIF. The scCO2-RESS process is a solvent free process, that can produce micronized or nanosized crystals able to improve physicochemical properties of poorly water-soluble drugs.


Assuntos
Dióxido de Carbono , Nifedipino , Solubilidade , Dióxido de Carbono/química , Tamanho da Partícula , Cristalização , Água
6.
J Cosmet Dermatol ; 21(10): 4921-4926, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35238148

RESUMO

INTRODUCTION: Ascorbic acid (AA) is a powerful antioxidant capable of acting significantly both in the prevention and treatment of the skin aging process. One way to assess the in vivo efficacy of anti-aging treatments is by using the high-frequency ultrasound (HFUS) skin image analysis technique, a non-invasive approach that allows for a new level of evaluating the effectiveness of dermatological and cosmetic products. The aim of the present study was to assess the performance of a topical emulsion of liquid crystalline structures containing AA using the 50 MHz HFUS skin image analysis method. METHODS: Twenty-five healthy female participants between 35 and 60 years were included, all of whom randomly applied a placebo formulation and an AA-containing formulation to each forearm, once a day, for 30 days. HFUS measurements were performed before using the products (T0), 2 h later (T2h), and after 30 days of use (T30d). The analyzed parameters included total skin, dermal, and epidermal echogenicity; variation and mean thickness of total skin, the epidermis and dermis; and surface roughness. Statistical analyses were performed using the Friedman test, followed by Dunn's test for comparisons of multiple means (α = 0.05). RESULTS: A significant increase in total skin and dermal echogenicity was observed after topical AA application. CONCLUSION: Our findings suggest that collagen synthesis significantly increased after topical therapy with AA, which was responsible for the increment in dermal echogenicity. This study showed, through the HFUS technique, that the topical use of AA promoted dermal redensification after 30 days of application.


Assuntos
Cosméticos , Envelhecimento da Pele , Humanos , Feminino , Ácido Ascórbico/farmacologia , Pele/diagnóstico por imagem , Ultrassonografia
7.
Eur J Pharm Sci ; 166: 105985, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34455087

RESUMO

Non-ideal behaviour of mixed ions is disclosed in skin absorption experiments of mixed halide anions in excised pig skin. Comparison of skin absorption of pure and mixed ions shows enhanced penetration of chaotropic ions from mixed solutions. An experimental design and statistical analysis using a Scheffé {3,2} simplex-lattice allows investigating the full ternary diagram of anion mixtures of fluoride, bromide and iodide. Synergism in mixed absorption is observed for chaotropic bromide and iodide anions. A refined analysis highlighting specific interactions is made by considering the ratio of the absorbed amount to the ion activity instead of the directly measured absorbed amount. Statistical analysis discards non-significant effects and discloses specific interactions. Such interactions between bromide and iodide cause an absorption enhancement of their partner by a factor of 2-3 with respect to the case of ideal mixing. It is proposed that enhanced absorption from mixed solution involves the formation of neutral complex species of mixed bromide and iodide with endogenous magnesium or calcium inside stratum corneum.


Assuntos
Absorção Cutânea , Água , Animais , Ânions/metabolismo , Fluoretos/metabolismo , Pele/metabolismo , Soluções , Suínos , Água/metabolismo
8.
Int J Cosmet Sci ; 43(4): 432-445, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33964042

RESUMO

OBJECTIVE: Pickering emulsions are increasingly used in the pharmaceutical and cosmetic fields, especially for topical applications, since these systems require solid particles as emulsifiers instead of surfactants which are known to cause skin irritation. The solid inorganic nanoparticles (TiO2 and ZnO) used as UV filters in sunscreen formulations may also stabilize emulsion droplets, so that the utility of surfactants may be questioned. Surfactant-free sunscreen emulsions solely stabilized by such nanoparticles (NPs) have been studied. METHODS: The ability of these NPs to stabilize o/w emulsions containing a 'model' oil phase, the C12 -C15 alkylbenzoate, has been assessed. ZnO and hydrophilic silica-coated TiO2 NPs widely used in sunscreen products were used together with their mixtures. The emulsification efficiency, the control of droplet size and the stability of o/w Pickering emulsions solely stabilized by NPs were investigated. A ZnO/TiO2 NPs mixture characterized by a theoretical SPF of 45 was finally used as unique emulsifiers to develop a surfactant-free sunscreen emulsion. RESULTS: Stable Pickering emulsions containing 10 up to 60 wt% of C12 -C15 alkyl benzoate were formulated with 2 wt% ZnO in the aqueous phase. The droplet size was controlled by the solid NPs content with respect to oil and the emulsification process. Hydrophilic TiO2 NPs did not allow the stabilization of emulsions. The substitution of TiO2 for ZnO up to 60-70 wt% in a 20/80 o/w emulsion was successfully performed. Finally, a ZnO/TiO2 NP mixture was tested as unique emulsifier system for the formulation of a sunscreen cream. Despite a lower viscosity, the obtained Pickering emulsion was stable and exhibited a photoprotective effect similar to the corresponding surfactant-based sunscreen cream with an in vitro SPF of about 45. CONCLUSION: Surfactant-free Pickering emulsions can be stabilized by the UV-filter nanoparticles for the manufacture of sunscreen products.


OBJECTIFS: Les émulsions de Pickering sont de plus en plus utilisées dans les domaines pharmaceutique et cosmétique, notamment pour les applications topiques, car ces systèmes utilisent des particules solides comme émulsifiants au lieu de tensioactifs qui sont connus pour provoquer des irritations cutanées. Les nanoparticules inorganiques solides (TiO2 et ZnO) utilisées comme filtres UV dans les formulations d'écran solaire peuvent également stabiliser les gouttelettes d'émulsion, de sorte que l'utilité des tensioactifs peut être remise en question. Des émulsions de protection solaire sans tensioactifs et uniquement stabilisées par de telles nanoparticules (NP) ont été étudiées. MÉTHODES: La capacité de ces NP à stabiliser les émulsions H/E contenant une phase huileuse «modèle¼, le benzoate d'alkyle C12 -C15 , a été évaluée. Des NP de ZnO et de TiO2 couvert de silice hydrophile, que l'on trouve largement dans les produits de protection solaire, ont été utilisées séparément et en mélange. L'efficacité d'émulsification, le contrôle de la taille des gouttelettes et la stabilité des émulsions de Pickering H/E uniquement stabilisées par les NP ont été étudiés. Un mélange de NP ZnO/TiO2 caractérisé par un SPF théorique de 45 a finalement été utilisé comme émulsifiant unique pour développer une émulsion de protection solaire sans tensioactif. RÉSULTATS: Des émulsions de Pickering stables contenant 10 à 60% en poids de benzoate d'alkyle C12 -C15 ont été formulées avec 2% en poids de ZnO dans la phase aqueuse. La taille des gouttelettes était contrôlée par la teneur en NP solides par rapport à l'huile et le procédé d'émulsification. Les NP de TiO2 hydrophile n'ont pas permis la stabilisation des émulsions. La substitution des NP de TiO2 par du ZnO jusqu'à 60-70% en poids dans une émulsion 20/80 H/E a été réalisée avec succès. Enfin, un mélange de NP ZnO/TiO2 a été testé en tant que système émulsifiant unique pour la formulation d'une crème solaire. Malgré une viscosité plus faible, l'émulsion de Pickering obtenue était stable et présentait un effet photoprotecteur similaire à la crème solaire à base de tensioactif correspondante avec un SPF in vitro d'environ 45. CONCLUSION: Les émulsions Pickering sans tensioactifs peuvent être stabilisées par les nanoparticules de filtre UV pour la formulation de produits de protection solaire.


Assuntos
Emulsões , Creme para a Pele/química , Protetores Solares/química , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas Metálicas/química , Microscopia Eletrônica de Transmissão , Tensoativos/química , Titânio/química , Óxido de Zinco/química
9.
Int J Pharm ; 592: 120092, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33212173

RESUMO

Emulsified systems are widely used for topical delivery with the aim of optimizing cutaneous absorption and offering a pleasant sensory. They also may provide a protection of the active molecule against oxidation and/or degradation. The oil phase of o/w emulsions may consist of liquid crystalline structures, especially lamellar structures which are similar to those found in the stratum corneum lipids. In the present work, o/w emulsions containing liquid crystals of mixed cetyl alcohol and Polysorbate 60 were developed for topical delivery of vitamin C, a potent antioxidant with several applications in the cosmetic and pharmaceutical fields. In addition to the well-documented lipid supplementation of the stratum corneum, the liquid crystal emulsions provide a significant chemical stabilization of vitamin C against its degradation. Emulsions were characterized by X-ray diffraction, polarized optical microscopy, and transmission electron microscopy. The stability of vitamin C in the formulations was evaluated upon storage in different conditions of temperature. The emulsions contain a complex colloidal structure, consisting of lamellar liquid crystalline (Lα) and crystalline lamellar gel (Lß) phases, that provide a very efficient protection of vitamin C against its degradation.


Assuntos
Cosméticos , Cristais Líquidos , Ácido Ascórbico , Emulsões , Absorção Cutânea
10.
Int J Pharm ; 591: 119991, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33091552

RESUMO

Skin constitutes a barrier protecting the organism against physical and chemical factors. Therefore, it is constantly exposed to the xenobiotics, including inorganic ions that are ubiquitous in the environment. Some of them play important roles in homeostasis and regulatory functions of the body, also in the skin, while others can be considered dangerous. Many authors have shown that inorganic ions could penetrate inside the skin and possibly induce local effects. In this review, we give an account of the current knowledge on the effects of skin exposure to inorganic ions. Beneficial effects on skin conditions related to the use of thermal spring waters are discussed together with the application of aluminium in underarm hygiene products and silver salts in treatment of difficult wounds. Finally, the potential consequences of dermal exposure to topical sensitizers and harmful heavy ions including radionuclides are discussed.


Assuntos
Absorção Cutânea , Pele , Íons/metabolismo , Prata/metabolismo , Pele/metabolismo
11.
Int J Pharm ; 583: 119373, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32339629

RESUMO

For several years, the international context is deeply affected by the use of chemical and biological weapons. The use of CBRN (Chemical Biological Radiological Nuclear) threat agents from military stockpiles or biological civilian industry demonstrate the critical need to improve capabilities of decontamination for civilians and military. Physical decontamination systems that operate only by adsorption and displacement such as Fuller's Earth, have the drawback of not neutralizing hazardous agents, giving place to cross contaminations. Consequently, the development of a formulation based on metal oxide nanoparticles attracts considerable interest, since they offer physicochemical properties that allow them to both adsorb and degrade toxic compounds. Thus, the aim of this study is to found metal oxide nanoparticles with a versatile activity on both chemical and biological toxic agents. Therefore, several metal oxides such as MgO, TiO2, CeO2, ZnO and ZrO2 were characterized and their decontamination kinetics of less-toxic surrogate of VX, paraoxon, were studied in vitro. To determine the antimicrobial activity of these nanoparticles, simulants of biological terrorist threat were used by performing a 3-hours decontamination kinetics. This proof-of-concept study showed that MgO is the only one that exhibits both chemical and antibacterial actions but without sporicidal activity.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Armas Biológicas , Substâncias para a Guerra Química/toxicidade , Descontaminação , Óxido de Magnésio/farmacologia , Nanopartículas Metálicas , Paraoxon/toxicidade , Antibacterianos/química , Bactérias/crescimento & desenvolvimento , Cério/farmacologia , Substâncias para a Guerra Química/química , Hidrólise , Cinética , Óxido de Magnésio/química , Modelos Químicos , Paraoxon/química , Estudo de Prova de Conceito , Titânio/farmacologia , Óxido de Zinco/farmacologia , Zircônio/farmacologia
12.
Int J Pharm ; 563: 79-90, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30825557

RESUMO

We present a systematic study of the role of poly(ethylene glycol) (PEG) content in NPs on drug skin absorption. Cholecalciferol-loaded NPs of 100 nm of diameter were prepared by flash nanoprecipitation from PLA-b-PEG copolymers of various PEG lengths. As PEG content increased in the polymer, we observed a transition from a frozen solid particle structure to a more dynamic particle structure. Skin absorption studies showed that polymer composition influenced drug penetration depending on skin condition (intact or impaired). In intact skin, highly PEGylated NPs achieved the best skin absorption, even if the penetration differences between the NPs were low. In impaired skin, on the contrary, non-PEGylated NPs (PLA NPs) promoted a strong drug deposition. Further investigations revealed that the strong drug accumulation from PLA NPs in impaired skin was mediated by aggregation and sedimentation of NPs due to the release of charged species from the skin. In contrast, the dynamic structure of highly PEGylated NPs promoted wetting of the surface and interactions with skin lipids, improving drug absorption in intact skin. Since NPs structure and surface properties determine the drug penetration mechanisms at the NP-skin interface, this work highlights the importance of properly tuning NPs composition according to skin physiopathology.


Assuntos
Colecalciferol/administração & dosagem , Lactatos/administração & dosagem , Nanopartículas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Absorção Cutânea , Pele/metabolismo , Animais , Colecalciferol/química , Feminino , Técnicas In Vitro , Lactatos/química , Peso Molecular , Nanopartículas/química , Polietilenoglicóis/química , Pele/lesões , Suínos
13.
Phys Chem Chem Phys ; 21(10): 5455-5465, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30801105

RESUMO

Repeated attacks using organophosphorus compounds, in military conflicts or terrorist acts, necessitate developing inexpensive and readily available decontamination systems. Nanosized cerium oxide is a suitable candidate, acting as a heterogeneous catalyst for the degradation of organophosphorus compounds such as VX agent or sarin. However, the reaction mechanism of the phosphatase mimetic activity of CeO2 nanoparticles is not fully described. Adsorption, surface-promoted hydrolysis, and desorption cycles strongly depend on the physico-chemical characteristics of the facets. In this study, CeO2 nanoparticles with different shapes were elaborated by hydrothermal synthesis. Nano-octahedra, nanocubes, or nanorods were selectively obtained under different conditions (temperature, concentration and nature of the precursors). The degradation activity according to the crystal faces was evaluated in vitro by measuring the degradation kinetics of paraoxon organophosphate in the presence of CeO2 nanoparticles. The results show an influence of both specific surface area and crystal faces of the nanoparticles, with higher activity for {111} facets compared to {100} facets at 32 °C. The relative activity between the facets is ascribed to the adsorption probability, assuming coordination between the phosphoryl oxygen and cerium atoms, but also to the surface density of the Ce doublets with relevant spacing for phosphatase mimetic activity.

14.
Int J Pharm ; 553(1-2): 120-131, 2018 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-30316003

RESUMO

We investigated the influence of nanoparticle (NP) surface composition on different aspects of skin delivery of a lipophilic drug: chemical stability, release and skin penetration. Cholecalciferol was chosen as a labile model drug. Poly(lactic acid) (PLA)-based NPs without surface coating, with a non-ionic poly(ethylene glycol) (PEG) coating, or with a zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) coating were prepared using flash nanoprecipitation. Process was optimized to obtain similar hydrodynamic diameters. Polymeric NPs were compared to non-polymeric cholecalciferol formulations. Cholecalciferol stability in aqueous medium was improved by polymeric encapsulation with a valuable effect of a hydrophilic coating. However, the in vitro release of the drug was found independent of the presence of any polymer, as for the drug penetration in an intact skin model. Such tendency was not observed in impaired skin since, when stratum corneum was removed, we found that a neutral hydrophilic coating around NPs reduced drug penetration compared to pure drug NPs and bare PLA NPs. The nature of the hydrophilic block (PEG or PMPC) had however no impact. We hypothesized that NPs surface influenced drug penetration in impaired skin due to different electrostatic interactions between NPs and charged skin components of viable skin layers.


Assuntos
Colecalciferol/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas , Polímeros/química , Administração Cutânea , Animais , Química Farmacêutica/métodos , Colecalciferol/farmacocinética , Portadores de Fármacos/química , Estabilidade de Medicamentos , Feminino , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Poliésteres/química , Polietilenoglicóis/química , Ácidos Polimetacrílicos/química , Absorção Cutânea , Eletricidade Estática , Suínos
15.
Int J Pharm ; 550(1-2): 170-179, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30118832

RESUMO

Clinical use of calcitriol (1,25-dihydroxyvitamin D3) as an anticancer agent is currently limited by the requirement of supraphysiological doses and associated hypercalcemia. Nanoencapsulation of calcitriol is a strategy to overcome these drawbacks, allowing reduced administrated doses and/or frequency, while retaining the therapeutic activity towards cancer cells. For this purpose, we investigated the impact of calcitriol encapsulation on its antiproliferative activity and optimized formulation parameters with that respect. Calcitriol-loaded polymeric nanoparticles with different polymer:oil ratios were prepared by the nanoprecipitation method. Nanoparticles had similar mean size (200 nm) and EE (85%) whereas their release profile strongly depended on formulation parameters. Antiproliferative and cytotoxic activities of formulated calcitriol were evaluated in vitro using human breast adenocarcinoma cells (MCF-7) and showed that calcitriol-induced cell growth inhibition was closely related to its release kinetics. For the most suitable formulation, a sustained cell growth inhibition was observed over 10 days compared to free form. Advantages of calcitriol encapsulation and the role of formulation parameters on its biological activity in vitro were demonstrated. Selected nanoparticle formulation is a promising calcitriol delivery system ensuring a prolonged anticancer activity that could improve its therapeutic efficiency.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Calcitriol/farmacologia , Portadores de Fármacos , Nanocápsulas , Polímeros , Antineoplásicos/uso terapêutico , Calcitriol/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Nanocápsulas/química
16.
Int J Pharm ; 531(1): 134-142, 2017 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-28802793

RESUMO

Surfactant-free biocompatible and biodegradable Pickering emulsions were investigated as vehicles for skin delivery of hydrophobic drugs. O/w emulsions of medium-chain triglyceride (MCT) oil droplets loaded with all-trans retinol as a model hydrophobic drug were stabilized by block copolymer nanoparticles: either poly(lactide)-block-poly(ethylene glycol) (PLA-b-PEG) or poly(caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG). Those innovative emulsions were prepared using two different processes allowing drug loading either inside oil droplets or inside both oil droplets and non-adsorbed block copolymer nanoparticles. Skin absorption of retinol was investigated in vitro on pig skin biopsies using the Franz cell method. Supplementary experiments by confocal fluorescence microscopy allowed the visualization of skin absorption of the Nile Red dye on histological sections. Retinol and Nile Red absorption experiments showed the large accumulation of hydrophobic drugs in the stratum corneum for the Pickering emulsions compared to the surfactant-based emulsion and an oil solution. Loading drug inside both oil droplets and block copolymer nanoparticles enhanced again skin absorption of drugs, which was ascribed to the supplementary contribution of free block copolymer nanoparticles loaded with drug. Such effect allowed tuning drug delivery to skin over a wide range by means of a suitable selection of either the formulation or the drug loading process.


Assuntos
Portadores de Fármacos/química , Emulsões/química , Absorção Cutânea , Animais , Etilenoglicóis , Lactatos , Micelas , Poliésteres , Polietilenoglicóis , Suínos
17.
Int J Radiat Biol ; 93(6): 607-616, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28276896

RESUMO

PURPOSE: To evaluate skin penetration and retention of americium (Am) and plutonium (Pu), in different chemical forms relevant to the nuclear industry and to treatment by chelation. MATERIALS AND METHODS: Percutaneous penetration of different Am and Pu forms were evaluated using viable pig skin with the Franz cell diffusion system. The behavior of the complex Pu-tributyl phosphate (Pu-TBP), Am or Pu complexed to the chelator Diethylene triamine pentaacetic acid (DTPA) and the effect of dimethyl sulfoxide (DMSO) was assessed. Radioactivity was measured in skin and receiver compartments. Three approaches were used to visualize activity in skin including the recent iQID technique for quantification. RESULTS: Transfer of Am was 24-fold greater than Pu and Pu-TBP complex penetration was enhanced by 500-fold. Actinide-DTPA transfer was greater than the Am or Pu alone (17-fold and 148-fold, respectively). The stratum corneum retained the majority of activity in all cases and both DMSO and TBP enhanced skin retention of Am and Pu, respectively. Histological and bioimaging data confirmed these results and the iQID camera allowed the quantification of skin activity. CONCLUSIONS: Skin penetration and fixation profiles are different depending on the chemical actinide form. Altered behavior of Pu-TBP and actinide-DTPA complexes reinforces the need to address decontamination protocols.


Assuntos
Elementos da Série Actinoide/farmacocinética , Quelantes/administração & dosagem , Absorção Cutânea/fisiologia , Pele/efeitos dos fármacos , Pele/metabolismo , Solventes/administração & dosagem , Absorção de Radiação/efeitos dos fármacos , Absorção de Radiação/fisiologia , Administração Tópica , Animais , Terapia por Quelação/métodos , Descontaminação/métodos , Técnicas In Vitro , Absorção Cutânea/efeitos dos fármacos , Suínos , Distribuição Tecidual/efeitos dos fármacos
18.
Chem Biol Interact ; 267: 57-66, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27129420

RESUMO

Organophosphorus compounds (OP), which mainly penetrate via the percutaneous pathway, represent a threat for both military and civilians. Body surface decontamination is vital to prevent victims poisoning. The development of a cost-effective formulation, which could be efficient and easy to handle in case of mass contamination, is therefore crucial. Metal oxides nanoparticles, due their large surface areas and the large amount of highly reactive sites, present high reactivity towards OP. First, this study aimed at evaluating the reaction of CeO2 nanoparticles, synthetized by microwave path and calcined at 500 or 600 °C, with Paraoxon (POX) in aqueous solution. Results showed that both nanoparticles degraded 60%-70% of POX. CeO2 calcined at 500 °C, owing to its larger specific area, was the most effective. Moreover, the degradation was significantly increased under Ultra-Violet irradiation (initial degradation rate doubled). Then, skin decontamination was studied in vitro using the Franz cell method with pig-ear skin samples. CeO2 powder and an aqueous suspension of CeO2 (CeO2-W) were applied 1 h after POX exposure. The efficiency of decontamination, including removal and/or degradation of POX, was compared to Fuller's earth (FE) and RSDL lotion which are, currently, the most efficient systems for skin decontamination. CeO2-W and RSDL were the most efficient to remove POX from the skin surface and decrease skin absorption by 6.4 compared to the control not decontaminated. FE reduced significantly (twice) the absorbed fraction of POX, contrarily to CeO2 powder. Considering only the degradation rate of POX, the products ranged in the order CeO2 > RSDL > CeO2-W > FE (no degradation). This study showed that CeO2 nanoparticles are a promising material for skin decontamination of OP if formulated as a dispersion able to remove POX like CeO2-W and to degrade it as CeO2 powder.


Assuntos
Cério/química , Descontaminação/métodos , Nanopartículas Metálicas/química , Paraoxon/toxicidade , Praguicidas/toxicidade , Pele/efeitos dos fármacos , Compostos de Alumínio/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Compostos de Magnésio/farmacologia , Nanopartículas Metálicas/ultraestrutura , Paraoxon/análise , Praguicidas/análise , Fotólise/efeitos da radiação , Silicatos/farmacologia , Pele/patologia , Creme para a Pele/farmacologia , Espectrofotometria Ultravioleta , Suínos , Raios Ultravioleta
19.
Soft Matter ; 12(36): 7564-76, 2016 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-27510805

RESUMO

The stabilization of o/w Pickering emulsions in cases of weak adsorption of solid particles at the surface of oil droplets is addressed. Though the adsorption is usually very strong and irreversible when partial wetting conditions are fulfilled, electrostatic repulsions between charged solid particles act against the adsorption. The regime of weak adsorption was reached using charged silica nanoparticles at high pH and low ionic strength. O/w Pickering emulsions of the diisopropyl adipate oil were stabilized by colloidal nanoparticles of Ludox® AS40 consisting of non-aggregated particles of bare silica (hydrophilic). The combination of stability assessment, droplet size and electrokinetic potential measurements at various pH values, adsorption isotherms and cryo-SEM observations of the adsorbed layers disclosed the specificities of the stabilization of Pickering emulsions by adsorption of solid nanoparticles against strong electrostatic repulsions. Not only the long-term stability of emulsions was poor under strong electrostatic repulsions at high pH, but emulsification failed since full dispersion of oil could not be achieved. Emulsion stability was ensured by decreasing electrostatic repulsions by lowering the pH from 9 to 3. Stable emulsions were stabilized by a monolayer of silica particles at 54% coverage of the oil droplet surface at low silica content and an adsorption regime as multilayers was reached at higher concentrations of silica although there was no aggregation of silica in the bulk aqueous phase.

20.
Pharm Res ; 33(7): 1564-75, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27015843

RESUMO

PURPOSE: Measurement of skin absorption of ions requires specific experimental protocols regarding the use of pig skin as a model, the viability of excised skin in water medium over 24 h, the presence of endogenous ions, and evaluation of the contributions of facilitated transport through ion channels and ion transporters. METHOD: Absorption experiments of halide anions F(-), Cl(-), Br(-) and I(-) in excised skin were performed in Franz diffusion cells. Experiments were performed on human and porcine skin under various conditions so as to define and validate experimental protocols. RESULTS: The distributions of endogenous ions and the absorption kinetics of halide ions were similar in both porcine and human skin models. Fresh skin kept its viability over 24 h in salt-free water, allowing experiments following OECD guidelines. Permeation increased in the order F(-) < Cl(-) < Br(-) < I(-) for all receptor media and skin samples. Absorption was larger in fresh skin due to the transport through chloride channels or exchangers. CONCLUSION: Skin absorption experiments of ions in Franz cells rely on working with fresh excised skin (human or porcine) and pure water as receptor fluid. Experiments with chloride blockers or frozen/thawed skin allow discriminating passive diffusion and facilitated transport.


Assuntos
Ânions/metabolismo , Absorção Cutânea/fisiologia , Pele/metabolismo , Animais , Difusão , Feminino , Humanos , Cinética , Masculino , Suínos , Água/metabolismo
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