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1.
Pharm Res ; 41(6): 1031-1044, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38740664

RESUMEN

Both intrinsic and extrinsic aging lead to a series of morphological changes in the skin including the flattening of the dermal-epidermal junction, increased stratum corneum dryness, reduction in sebaceous gland activity and enzyme activity as well as atrophy of blood vessels. In this study, the impact of these changes on the transport of molecules through the skin was revised. The increase in the number of transdermal formulations on the market in recent decades and life expectancy represent the main reasons for an in-depth discussion of this topic. Furthermore, elderly subjects have often been excluded from clinical trials due to polypharmacy, raising concerns in terms of efficacy and safety. In this way, ex vivo and in vivo studies comparing the transport of molecules through the mature and young skin were analyzed in detail. The reduced water content in mature skin had a significant impact on the transport rate of hydrophilic molecules. The lower enzymatic activity in aged skin, in turn, would explain changes in the activation of prodrugs. Interestingly, greater deposition of nanoparticles was also found in mature skin. In vivo models should be prioritized in future experimental studies as they allow to evaluate both absorption and metabolism simultaneously, providing more realistic information.


Asunto(s)
Administración Cutánea , Envejecimiento , Absorción Cutánea , Piel , Humanos , Piel/metabolismo , Envejecimiento/metabolismo , Animales , Transporte Biológico , Nanopartículas/metabolismo , Nanopartículas/química , Envejecimiento de la Piel , Preparaciones Farmacéuticas/metabolismo , Preparaciones Farmacéuticas/administración & dosificación , Profármacos/farmacocinética , Profármacos/metabolismo
2.
Pharm Res ; 40(5): 1209-1221, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36959412

RESUMEN

Ethical restrictions as well as practical or economic issues related to use of animal and human skin has been the main reason the growth in the number of investigations with alternative models. Reconstructed skin models, for example, have been useful to evaluate the in vitro toxicity of compounds; however, these models usually overestimate the amount of drug permeated due to impaired barrier properties. In this review, the performance of synthetic and biological skin models in transport studies was compared by considering two compounds with different physicochemical properties. The advantages and limitations of each skin model are discussed in detail. Although synthetic and reconstructed skin models have shown to be useful in the formulation optimization step, they present many limitations: (1) impaired barrier properties; (2) lack of follicular transport; (3) no metabolism in synthetic membranes; (4) differences in terms of lipid organization; (5) more affected by formulation constituents. Therefore, animal and human tissues should still be prioritized in drug transport studies until new advances in alternative models are achieved. Investigations of the impact of cell-culture conditions on skin formation, in turn, bring perspectives related to the development of unhealthy/injured skin models (an aspect that still deserves attention).


Asunto(s)
Absorción Cutánea , Piel Artificial , Animales , Humanos , Administración Cutánea , Piel/metabolismo , Transporte Biológico , Modelos Biológicos , Permeabilidad
3.
Pharm Res ; 37(12): 240, 2020 Nov 09.
Artículo en Inglés | MEDLINE | ID: mdl-33169237

RESUMEN

Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin. Graphical abstract.


Asunto(s)
Antiinfecciosos/administración & dosificación , Antiinflamatorios/administración & dosificación , Dapsona/administración & dosificación , Portadores de Fármacos/química , Enfermedades de la Piel/tratamiento farmacológico , Administración Cutánea , Animales , Química Farmacéutica , Cristalización , Modelos Animales de Enfermedad , Composición de Medicamentos/métodos , Humanos , Nanopartículas/química , Piel/metabolismo , Absorción Cutánea , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/microbiología
4.
AAPS PharmSciTech ; 21(8): 289, 2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33079291

RESUMEN

The oral administration of isoniazid (INH) may lead to discontinuation of tuberculosis treatment due to drug-related hepatotoxicity events, and thus, the transbuccal delivery of this drug was investigated, for the first time, as an alternative administration route. Ex vivo permeability assays were performed in Franz-type diffusion chambers, applying INH alone and in combination with sodium dodecyl sulfate (SDS) and sodium taurocholate (ST). After confirming the formation of micelle structures by dynamic light scattering analysis, UV-visible spectroscopy and zeta potential analyses were used to investigate drug-micelle interactions. In zeta potential analyses, no electrostatical interactions were identified for both surfactants in saliva buffer pH 6.8. Spectrophotometric analyses, in turn, indicated chemical interactions between INH and SDS in both pH values (2.0 and 6.8) whereas no interaction between the drug and ST was observed. Despite the interaction between SDS and drug, this surfactant increased the buccal transport rate of INH by approximately 11 times when compared with the control. In contrast, ST did not increase the drug permeability. The INH retention in SDS-treated mucosa was significantly higher when compared with the control and an effect on intercellular lipids was suggested. In vivo studies are needed to confirm the high INH absorption found here. Grapical abstract.


Asunto(s)
Antituberculosos/administración & dosificación , Isoniazida/administración & dosificación , Mucosa Bucal/efectos de los fármacos , Dodecil Sulfato de Sodio/química , Tensoactivos/química , Difusión , Interacciones Farmacológicas , Micelas , Mucosa Bucal/metabolismo , Permeabilidad/efectos de los fármacos , Ácido Taurocólico/farmacología
5.
AAPS PharmSciTech ; 19(1): 192-200, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-28681331

RESUMEN

We have recently shown that coumestrol, an isoflavonoid-like compound naturally occurring in soybeans, alfafa, and red clover, inhibited Herpes Simplex Virus types 1 (HSV-1) and 2 (HSV-2) replication. In this study, we designed coumestrol formulations in an attempt to enable its topical delivery to mucosa tissues. Physicochemical and microscopic examinations suggested that coumestrol was efficiently incorporated in positively-charged nanoemulsions dispersed in a hydroxyethylcellulose gel. The higher coumestrol flux through excised porcine esophageal mucosa was detected from nanoemulsions composed by a fluid phospholipid (dioleylphosphocholine, DOPC) in comparison with that of a rigid one (distearoylphosphocholine, DSPC) in two mucosa conditions (intact and injured). Such results were supported by confocal fluorescence images. Furthermore, the low IC50 values demonstrated an increasement in the antiviral inhibition against HSV-1 and HSV-2 after incorporation of coumestrol into nanoemulsions containing DOPC. Overall, coumestrol-loaded nanoemulsions proved to be beneficial for herpes simplex treatment.


Asunto(s)
Antivirales/administración & dosificación , Cumestrol/administración & dosificación , Herpesvirus Humano 1/efectos de los fármacos , Herpesvirus Humano 2/efectos de los fármacos , Administración Tópica , Animales , Antivirales/química , Antivirales/metabolismo , Antivirales/farmacología , Celulosa/análogos & derivados , Celulosa/química , Cumestrol/metabolismo , Cumestrol/farmacología , Emulsiones , Membrana Mucosa/metabolismo , Fosforilcolina/química , Porcinos
6.
Int J Biol Macromol ; 268(Pt 2): 131880, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38677707

RESUMEN

Injectable hyaluronic acid (HA) hydrogels have been popularized in facial aesthetics as they provide a long-lasting effect, low risk of complications, allergenicity tests are not required before application and can be easily removed by the action of hyaluronidases. On the other hand, the development of these systems requires in-depth studies of chemical mechanisms involved in hydrogel formation. Ideal dermal fillers should temporarily fluidize during extrusion through the needle and quickly recover their original shape after application. Hydrogels with more elastic properties, for example, are difficult to inject while viscous materials are too liquid. A balance between both properties should be achieved. Each region of the face requires products with distinct rheological properties. High G' dermal fillers are preferable for deeper wrinkles whereas the counterpart with lower values of G' is more indicated in superficial wrinkles or lip augmentation. Factors such as molecular weight and concentration of HA, pH, type and concentration of the crosslinking agent, particle size, crosslinking reaction time and crosslinking agent/polysaccharide ratio should be modulated to achieve specific rheological properties. In this review, the effect of each variable is discussed in detail to guide the rational development of new dermal fillers.


Asunto(s)
Rellenos Dérmicos , Ácido Hialurónico , Hidrogeles , Reología , Ácido Hialurónico/química , Hidrogeles/química , Rellenos Dérmicos/química , Rellenos Dérmicos/administración & dosificación , Humanos , Cara , Inyecciones
7.
Drug Deliv Transl Res ; 14(5): 1239-1252, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38227165

RESUMEN

Sepsis represents a complex clinical syndrome that results from a harmful host response to infection. The infections most associated with sepsis are pneumonia, intra-abdominal infection, and urinary tract infection. Tea tree oil (TTO) has shown high antibacterial activity; however, it exhibits low aqueous solubility and high volatility, which have motivated its nanoencapsulation. In this study, the performance of nanoemulsions (NE) and nanocapsules (NC) loaded with TTO was compared. These systems were prepared by spontaneous emulsification and nanoprecipitation methods, respectively. Poly-ε-caprolactone or Eudragit® RS100 were tested as polymers for NCs whereas Tween® 80 or Pluronic® F68 as surfactants in NE preparation. Pluronic® F68 and Eudragit® RS100 resulted in more homogeneous and stable nanoparticles. In accelerated stability studies at 4 and 25 °C, both colloidal suspensions (NC and NE) were kinetically stable. NCs showed to be more stable to photodegradation and less cytotoxic than NEs. After sepsis induction by the cecal ligation and puncture (CLP) model, both NE and NC reduced neutrophil infiltration into peritoneal lavage (PL) and kidneys. Moreover, the systems increased group thiols in the kidney and lung tissue and reduced bacterial growth in PL. Taken together, both systems showed to be effective against injury induced by sepsis; however, NCs should be prioritized due to advantages in terms of cytotoxicity and physicochemical stability.


Asunto(s)
Melaleuca , Nanocápsulas , Ácidos Polimetacrílicos , Sepsis , Aceite de Árbol de Té , Aceite de Árbol de Té/farmacología , Poloxámero , Sepsis/tratamiento farmacológico
8.
Int J Biol Macromol ; 275(Pt 2): 133356, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38945715

RESUMEN

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.


Asunto(s)
Antifúngicos , Candidiasis Vulvovaginal , Fluconazol , Timol , Femenino , Candidiasis Vulvovaginal/tratamiento farmacológico , Candidiasis Vulvovaginal/microbiología , Fluconazol/farmacología , Fluconazol/química , Fluconazol/administración & dosificación , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/administración & dosificación , Biopolímeros/química , Timol/química , Timol/farmacología , Farmacorresistencia Fúngica/efectos de los fármacos , Humanos , Quitosano/química , Pruebas de Sensibilidad Microbiana , Animales , Portadores de Fármacos/química , Permeabilidad , Candida glabrata/efectos de los fármacos
9.
Eur J Pharm Sci ; 159: 105722, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33482314

RESUMEN

Secnidazole (SEC) has been suggested as an alternative agent against Trichomonas vaginalis to overcome the adverse effects, antimicrobial resistance problems and poor adherence to the currently available therapy. Once no topical formulation may be found in the market until now, SEC was incorporated in thermosensitive bioadhesive systems to extend the contact time in the mucosa and to avoid a systemic drug disposition. Formulations containing 20% poloxamer 407, 1% poloxamer 188 and 1 or 2.5% chitosan showed suitable sol-gel transition temperature (> 30 °C), presenting a fast gelation time (100-115 s). Rheological, dynamic light scattering and infrared spectroscopy analysis suggested molecular interactions among polymers. Chitosan increased the mucoadhesion strength of the formulations. In addition, hydrogels showed a tendency to decrease the drug transport rate through mucosa when compared to the control. Mucin was also added onto mucosa for a more realistic simulation of permeability/retention. In the presence of this agent, hydrogels containing chitosan reduced the permeability/retention of the drug in approximately 2.0-fold when compared to the control. Therefore, the hydrogels presented suitable characteristics to remain in the vaginal environment, which would result in effective local treatment of trichomoniasis.


Asunto(s)
Hidrogeles , Poloxámero , Parto Obstétrico , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Metronidazol/análogos & derivados , Embarazo , Temperatura
10.
Mater Sci Eng C Mater Biol Appl ; 119: 111546, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33321611

RESUMEN

Given that oral preparations of benznidazole (BZN) have demonstrated limited efficacy in the treatment of Chagas' disease due to pharmacokinetic or toxicological problems, the development of buccal polymeric films was purposed in this study. These systems ensure high patient acceptability and direct access to the systemic circulation, improving drug bioavailability and toxicological profile. Polymer films were prepared through a thermopressing method by mixing BZN and polyvinyl alcohol (PVAL). In some preparations, propylene glycol (PG) and thymol (TM) were also included as plasticizer and chemical absorption enhancer, respectively. Morphology, X-ray diffraction, spectroscopic, thermal, mechanical, and water uptake properties, as well as ex vivo permeability studies, were performed to characterize the film formulations. BZN remained stable and in an amorphous form over 90 days. The addition of PG and TM improved the mechanical properties of the films, making them soft, flexible and tear-resistant. Also, these additives increased the water sorption rate of the films at 50 and 75% relative humidity and the TM increased the film erosion properties and drug permeability (close to 6×) compared to control. It was hypothesized that the permeability improvement of thymol-based films that follow a drug release profile through erosion is also associated with the inhibition of the crystallization of BNZ when the film is in contact with the buccal mucosa. Once the thymol has previously demonstrated a significant in vivo and in vitro trypanocidal action and even improved film characteristics, these systems may be considered promising for Chagas' disease treatment.


Asunto(s)
Nitroimidazoles , Alcohol Polivinílico , Composición de Medicamentos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos
11.
Eur J Pharm Sci ; 143: 105177, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31812716

RESUMEN

Benznidazole (BZN) represents the only drug currently available for the treatment of Chagas disease in most endemic countries. When administered orally, high doses are required due to its extensive hepatic metabolism and its toxicity represents the main reason for treatment withdrawals. Because of these complications, transbuccal administration of BZN was investigated. This route avoids the first-pass hepatic metabolism and presents high permeability, with direct access to the systemic circulation. BZN was applied on porcine buccal mucosa after pretreatment with pure eugenol, carvacrol or limonene. Thermal (DSC) and spectroscopic (FT-IR) analyzes were performed to investigate the mechanisms of drug absorption enhancement. The permeability coefficient values of BZN increased 2.6, 2.9 and 4.9-fold after pretreatment with eugenol, carvacrol and limonene, respectively. The lag time, in turn, was shortened in the pretreated samples. The DSC and FT-IR analyzes suggested that transport of BZN through the buccal mucosa is associated with log P and size of monoterpenes. Limonene, the most effective absorption enhancer, contributed to greater interaction with non-polar domains of the buccal epithelium. Overall, BZN showed to be efficiently transported through the buccal route, but in vivo pharmacokinetic studies should be performed to confirm these findings.


Asunto(s)
Monoterpenos/administración & dosificación , Mucosa Bucal/metabolismo , Nitroimidazoles/administración & dosificación , Tripanocidas/administración & dosificación , Administración Bucal , Animales , Permeabilidad , Porcinos
12.
Int J Biol Macromol ; 163: 167-179, 2020 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-32615217

RESUMEN

The emergence of new materials with improved antibacterial, anti-inflammatory and healing properties compared to conventional wound dressings has both social and economic appeal. In this study, novel chitosan-based (CTS) membranes containing curcumin (CUR) incorporated in Pluronic (PLU) copolymers were developed and characterized to obtain suitable properties for applications as a wound healing dressing. The mechanical, thermal, swelling, wettability, release and permeation properties were evaluated by DSC, TGA, water contact angle measurements, FTIR, fluorescence and microscopic techniques. Membranes containing PLU and CUR presented wettability close to the ideal range for interaction with cellular components (contact angle ~40-70°), improved mechanical properties, higher thermal stability, high swelling degree (>800%) and CUR release (~60%) compared to samples without PLU addition. A higher retention of CUR in the epidermis than in the dermis layer was observed, which also was confirmed by confocal microscopy. Furthermore, the CTS-PLU membranes loaded with CUR showed to be active against Staphylococcus aureus and Pseudomonas aeruginosa (MIC = 25 and 100 mg mL-1, respectively), the microbial species most present in chronic wounds. Overall, the CTS-PLU-CUR membranes presented suitable properties to act as a new wound healing dressing formulation and in vivo studies should be performed to confirm these benefits.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacocinética , Quitosano/análogos & derivados , Curcumina/química , Curcumina/farmacocinética , Membranas/química , Antibacterianos/farmacología , Vendajes/microbiología , Rastreo Diferencial de Calorimetría , Quitosano/química , Quitosano/farmacocinética , Curcumina/farmacología , Liberación de Fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Microscopía Confocal , Pseudomonas aeruginosa/efectos de los fármacos , Piel/diagnóstico por imagen , Piel/efectos de los fármacos , Piel/patología , Espectroscopía Infrarroja por Transformada de Fourier , Staphylococcus aureus/efectos de los fármacos , Propiedades de Superficie , Termogravimetría , Agua/química , Cicatrización de Heridas/efectos de los fármacos
13.
Nat Prod Res ; 32(4): 486-492, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28403634

RESUMEN

The aim of the present study was to develop a phytocosmetic using Vitis waste by-products, for use as a topical formulation for skin protection against ultraviolet radiation damage. The study also evaluates the free radical scavenger activity of the crude extracts of dried leaves of Vitis vinifera and Vitis labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds. Next, release and permeation studies of hydrogels were performed using Franz-type diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes antioxidant assays, whereas anthocyanins had higher antioxidant activity in hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released from hydrogels, and the flavonoid retention in porcine ear skin after eight hours of permeation was below of limit of quantification for this compound. The polyphenols present in Vitis are capable of absorbing UV and visible light, justifying their potential as sunscreens for the development of a phytocosmetic.


Asunto(s)
Antioxidantes/farmacología , Hojas de la Planta/química , Polifenoles/farmacología , Vitis/química , Animales , Antocianinas/análisis , Antioxidantes/química , Evaluación Preclínica de Medicamentos/métodos , Liberación de Fármacos , Flavonoides/análisis , Flavonoides/farmacología , Industria de Alimentos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/farmacología , Hidrogeles/farmacocinética , Polifenoles/análisis , Quercetina/análogos & derivados , Quercetina/farmacocinética , Absorción Cutánea/efectos de los fármacos , Protectores Solares/química , Porcinos , Rayos Ultravioleta
14.
Biomed Res Int ; 2015: 238010, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26101767

RESUMEN

This study investigated the inhibitory effects of Achyrocline satureioides extract (ASE) incorporated into a topical nanoemulsion on Herpes Simplex Virus type 1 (HSV-1/KOS strain) replication, as well as the distribution of the main ASE flavonoids (quercetin, luteolin, and 3-O-methylquercetin) in porcine skin and mucosa. The ASE-loaded nanoemulsion showed more pronounced effects against HSV-1 replication when compared to the ASE or pure quercetin, as determined by the viral plaque number reduction assay. All flavonoids were detected in the skin epidermis (2.2 µg/cm(2)) and the mucosa upper layers (3.0 µg/cm(2)) from ASE-loaded nanoemulsion until 8 h after topical application. A higher amount of flavonoids was detected when these tissues were impaired, especially in deeper mucosa layers (up to 7-fold). Flavonoids were detected in the receptor fluid only when the mucosa was injured. Such results were supported by confocal microscopy images. Overall, these findings suggest that the tested ASE-loaded nanoemulsion has potential to be used topically for herpes infections.


Asunto(s)
Emulsiones/administración & dosificación , Flavonoides/administración & dosificación , Membrana Mucosa/efectos de los fármacos , Piel/efectos de los fármacos , Achyrocline/química , Administración Tópica , Animales , Emulsiones/química , Flavonoides/química , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Porcinos
15.
Int J Nanomedicine ; 10: 5529-42, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26366075

RESUMEN

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 2(2) full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant - soybean lecithin or sorbitan monooleate and type of co-surfactants - polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential -39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g(-1)) - the main response of interest - confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.


Asunto(s)
Antiparasitarios/farmacología , Chalcona/farmacología , Sistemas de Liberación de Medicamentos , Leishmaniasis Cutánea/tratamiento farmacológico , Nanoestructuras/química , Administración Cutánea , Antiparasitarios/química , Línea Celular Tumoral , Chalcona/química , Fenómenos Químicos , Emulsiones , Humanos , Concentración de Iones de Hidrógeno , Concentración 50 Inhibidora , Lecitinas/química , Lecitinas/farmacología , Tamaño de la Partícula , Polisorbatos/química , Polisorbatos/farmacología , Piel/efectos de los fármacos , Piel/parasitología , Solubilidad , Relación Estructura-Actividad , Tensoactivos/química , Tensoactivos/farmacología , Viscosidad
16.
Int J Nanomedicine ; 9: 4737-47, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25336951

RESUMEN

The aim of this study was to optimize topical nanoemulsions containing genistein, by means of a 23 full factorial design based on physicochemical properties and skin retention. The experimental arrangement was constructed using oil type (isopropyl myristate or castor oil), phospholipid type (distearoylphosphatidylcholine [DSPC] or dioleylphosphaditylcholine [DOPC]), and ionic cosurfactant type (oleic acid or oleylamine) as independent variables. The analysis of variance showed effect of third order for particle size, polydispersity index, and skin retention of genistein. Nanoemulsions composed of isopropyl myristate/DOPC/oleylamine showed the smallest diameter and highest genistein amount in porcine ear skin whereas the formulation composed of isopropyl myristate/DSPC/oleylamine exhibited the lowest polydispersity index. Thus, these two formulations were selected for further studies. The formulations presented positive ζ potential values (>25 mV) and genistein content close to 100% (at 1 mg/mL). The incorporation of genistein in nanoemulsions significantly increased the retention of this isoflavone in epidermis and dermis, especially when the formulation composed by isopropyl myristate/DOPC/oleylamine was used. These results were supported by confocal images. Such formulations exhibited antiherpetic activity in vitro against herpes simplex virus 1 (strain KOS) and herpes simplex virus 22 (strain 333). Taken together, the results show that the genistein-loaded nanoemulsions developed in this study are promising options in herpes treatment.


Asunto(s)
Antivirales/química , Emulsiones/química , Genisteína/química , Herpesvirus Humano 1/efectos de los fármacos , Nanopartículas/química , Fosfolípidos/química , Animales , Antivirales/farmacología , Química Farmacéutica , Emulsiones/farmacología , Genisteína/farmacología , Oxazinas , Tamaño de la Partícula , Proyectos de Investigación , Piel , Absorción Cutánea , Porcinos
17.
J Chromatogr Sci ; 50(2): 114-8, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22298760

RESUMEN

Recent studies have shown the effect of soy isoflavones in preventing skin photoaging and photocarcinogenesis, especially for genistein (GEN). Nanoemulsions have been proposed as a delivery system for GEN administration due to the low water solubility of this isoflavone. This article describes the validation of an isocratic liquid chromatography method to determine GEN in porcine ear skin layers from nanoemulsions before and after incorporation into hydrogels. The analyses are performed on a reversed-phase C18 column using a mobile phase composed of methanol-water (70:30, v/v) under acid conditions (at pH 3.0) and UV detection at 270 nm. The method is linear in the range of 0.1-10 µg/mL (r(2) > 0.999) in the presence of skin extracts. The low limit of quantitation is estimated as 0.1 µg/mL. No interferences from formulation excipients or skin layer compounds are detected. The RSD values for intra- and inter-day precision are lower than 15%. Recovery ranged from approximately 90% to 110%. The method is applied to estimate GEN retention in the skin from formulations using Franz diffusion cells. The highest amount of GEN is detected in the epidermis (185 µg/cm(2)). In conclusion, the method proved to be specific, precise, and accurate in determining GEN amounts from formulations in skin retention studies.


Asunto(s)
Cromatografía Liquida/métodos , Emulsiones , Genisteína/metabolismo , Hidrogeles , Piel/metabolismo , Animales , Nanoestructuras , Reproducibilidad de los Resultados , Espectrofotometría Ultravioleta , Porcinos
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