Influence of monoolein on progesterone transdermal delivery

abstract This work aimed to investigate in vitro the influence of monoolein (MO) on progesterone (PG) transdermal delivery and skin retention. Information about the role of MO as an absorption enhancer for lipophilic molecules can help on innovative product development capable of delivering the hormone through the skin in a consistent manner, improving transdermal therapy of hormonal replacement. MO was dispersed in propylene glycol under heat at concentrations of 0% (control), 5% w/w, 10% w/w and 20% w/w. Then, 0.6% of PG (w/w) was added to each formulation. Permeation profile of the hormone was determined in vitro for 48 h using porcine skin in Franz diffusion cells. PG permeation doubled when 5% (w/w) of MO was present in formulation in comparison to both the control and higher MO concentrations (10% and 20% w/w). An equal trend was observed for PG retention in stratum corneum (SC) and reminiscent skin (E+D). PG release rates from the MO formulations, investigated using cellulose membranes, revealed that concentrations of MO higher than 5% (w/w) hindered PG release, which indeed negatively reflected on the hormone permeation through the skin. In conclusion, this work demonstrated the feasibility of MO addition (at 5% w/w) in formulations as a simple method to increase transdermal PG delivery for therapies of hormonal replacement. In contrast, higher MO concentrations (from 10% to 20% w/w) can control active release, and this approach could be extrapolated to other lipophilic, low-molecular-weight molecules.

resumo Este trabalho teve como objetivo investigar in vitro a influência de monooleína (MO) na permeação transdérmica de progesterona (PG), bem como sobre a retenção cutânea desse hormônio a fim de (i) liberar de maneira mais consistente hormônio através da pele para melhorar a terapia transdérmica de reposição hormonal e (ii) trazer mais informações sobre o papel da MO como promotor da absorção cutânea de moléculas lipofílicas, tema ainda pouco explorado na literatura. MO foi dispersa em propilenoglicol, a concentrações de 0% (controle), 5%, 10% e 20% (p/p). Adicionou-se, em seguida, 0,6% (p/p) de PG a cada uma das formulações. O perfil de permeação do hormônio foi então determinado in vitro durante 48 h, utilizando pele de porco em células de difusão do tipo Franz. MO a 5% (p/p) foi capaz de duplicar a permeação de PG em comparação ao controle e às concentrações mais elevadas de MO, assim como a retenção de PG no estrato córneo (SC) e epiderme e derme remanescentes (E+D). A velocidade de liberação de PG a partir das formulações foi investigada usando membranas de celulose e este estudo revelou que concentrações de MO superiores a 5% (p/p) impediram a liberacão de PG, o que de fato refletiu de forma negativa na permeação cutânea do hormônio. Concluindo, este trabalho demonstrou a viabilidade da adição de MO a uma formulação como um método simples para aumentar a permeação transdérmica de PG para uso em terapias de reposição hormonal. Por outro lado, altas concentrações de MO (de 10% a 20% p/p) controlam a liberação de PG e este efeito pode ser extrapolado para outras moléculas lipofílicas de baixa massa molecular.

Caracterização do intumescimento de sistemas líquido-cristalinos de fase lamelar de monoleína e água contendo polihexametilenobiguanida / Characterization of swelling of lamellar phases of monoolein and water containing polyhexamethylenebiguanide

A monoleína é um lipídeo polar capaz de absorver água e formar sistemas líquido-cristalinos, os quais são utilizados como sistemas de liberação para administração de vários fármacos. Neste estudo foi avaliado o potencial de sistemas de fase lamelar constituídos por monoleína e água para veicular polihexametilenobiguanida (PHMB). A formação dos sistemas líquido-cristalinos foi caracterizada por microscopia de luz polarizada. Estudos de intumescimento foram realizados gravimetricamente em várias condições avaliando-se os efeitos de parâmetros como pH, força iônica e temperatura do meio de imersão. O processo de intumescimento foi caracterizado através da obtenção dos perfis de intumescimento e análise de sua cinética, além da determinação da capacidade máxima de intumescimento dos sistemas. Os sistemas de fase lamelar foram obtidos em presença de PHMB, os quais absorveram água rapidamente de acordo com cinética de segunda ordem e sofreram transição de fase, formando a fase cúbica. O intumescimento dos sistemas não foi influenciado pela presença do fármaco nos vários meios de imersão estudados, exceto pela imersão em meio ácido, no qual a presença do PHMB aumentou a captação de água. O intumescimento dos sistemas contendo PHMB não foi afetado pela força iônica do meio de imersão, porém foi diminuído com o aumento da temperatura. Desta maneira, sistemas líquido-cristalinos de monoleína e água foram obtidos e o processo de intumescimento foi caracterizado. Os sistemas apresentaram potencial para serem propostos como sistemas de liberação para administração de PHMB e estudos de liberação de fármacos serão realizados futuramente.

Monoolein is a polar lipid that absorbs water and forms liquid crystalline systems that are used as drug delivery systems for different medications. The aim of the present study was to investigate lamellar phases formed by monoolein and water as potential vehicles for the administration of polyhexamethylene biguanide (PHMB). Lamellar phase systems formed by monoolein and water containing PHMB were characterized by polarizing microscopy. Swelling studies were performed gravimetrically under different conditions for the evaluation of the effects of pH, ionic strength and temperature. Analyses of swelling profiles, swelling kinetics and maximum swelling capacity were performed. The lamellar phase systems of monoolein and water obtained in the presence of PHMB absorbed water very quickly following second-order swelling kinetics and formed a cubic phase. The swelling of the systems was not influenced by the presence of the drug in the immersion media studied, except under acidic conditions, in which the drug exhibited increased water uptake. The swelling of systems containing PHMB was not affected by the ionic strength of the immersion media, but was reduced with an increase in temperature. Liquid crystalline systems of monoolein and water were obtained and swelling behavior was investigated. The systems exhibited the potential for use as a drug delivery system for PHMB administration. However, further drug-release studies should be performed.

Study of the Inhibitory Effect of <i>Coix lachryma-jobi</i> L. <i>var. ma-yuen</i> Stapf on Carcinogenesis and Inflammation / 日本補完代替医療学会誌

Adlay(<i> Coix lachryma-jobi</i> L. <i>var. ma-yuen</i> Stapf ) is a grass crop that has long been used in traditional medicine as a nourishing food. This study investigated the inhibitory effects of adlay related substances on carcinogenesis and anti-inflammation. The hot water extract of all parts of adlay (CRD) were compared with the hot water extract of dehulled adlay (yokuinin). In addition, the Monoolein and Trilinolein components of adlay were compared.<br> As a screening date, antiproliferative effect of human cancer cells showed weak biological potency on physical dose response. Prevention effect of carcinogenesis and anti-inflammatory effect were also observed in all samplles. CRD showed stronger anti-UVB inflammatory effect than that of yokuinin; while yokuinin showed stronger anti-heating injury inflammatory effect than that of CRD. Moreover, Monoolein showed stronger effect than Trilinolein on both prevention effect of carcinogenesis and anti-inflammatory effect. These result indicated that these two extracts of adlay exhibited inhibitory effect on both tumor and inflammation. In addition, it is also suggested that Monoolein is more effective than Trilinolein.<br>

Cubosomes as drug delivery system: Recent advance / 第二军医大学学报

Cubosomes are self-assembled nanostructured particles formed by aqueous lipid and surfactant systems. Cubosomes are thermodynamically stable; they have a structure like "honeycombed" with bicontinuous domains of water and lipid in which surfactant assembles into bilayers and twisted into a three dimension, periodic, and minimal surface, forming a tightly packed structure. The properties of cubosomes, such as its unique bicontinuous cubic phase liquid crystals, its ability to solubilize hydrophobic, hydrophilic, and amphiphilic molecules at the same time, its biodegradability by simple enzyme action, its strong bioadhesion ability, and its simple preparation, make them a promising vehicle for drug delivery. Based on recent reports, this review introduces the structure, preparation, exosyndrome and drug delivery potential of cubosomes.

Histological Evaluation of the Bone Repair Using Mineral Trioxide Aggregate Combined to a Material Carrier / Evaluación Histológica del Proceso de Reparación Ósea Utilizando Agregado Trióxido Mineral Combinado a un Material Cargador

The aim of this study was to present a possible carrier for MTA, monoolein gel, with the objective to maintain this material in the place that was inserted and verify if this procedure is able to optimize its action. The data were evaluated by histomorphometric method and submitted to statistical analysis. The histological responses observed in this study indicate that the MTA is a reliable material and should be considered effective in bone periapical defects and the monoolein gel was capable to maintain the MTA in situ.

El objetivo de este estudio fue presentar el gel de monoleína como un posible cargador para el MTA y verificar si es capaz de optimizar su acción. Los datos obtenidos fueron evaluados por métodos histomorfométricos y sometidos a análisis estadístico. El resultado histológico reveló que el MTA es un material efectivo para utilizarlo en defectos óseos periapicales y que el gel de monoleína es capaz de mantener el MTA in situ.