Attainment of O/W emulsions containing liquid crystal from annatto oil (Bixa orellana), coffee oil, and tea tree oil (Melaleuca alternifolia) as oily phase using HLB system and ternary phase diagram

Emulsions containing liquid crystals present interesting properties and advantages such as the skin moisturize increase, active release modulation, and emulsion stabilization. In this work, emulsions containing annatto, coffee and tea tree oils, and nonionic surfactants were developed. The HLB method was used for selection of surfactants. The required HLB value was established (9.0). Liquid crystals were attained when used the surfactant mixture Ceteareth-5 and Steareth-2 and identified as lamellar. The emulsions showed pseudoplastic behavior and tixotropy. The ternary diagram was useful in the selection of the proportion of surfactant and oily phase considering skin compatibility and liquid crystal presence.

Development of Vegetable Oil Emulsions with Lamellar Liquid-Crystalline Structures

Emulsions containing vegetable oils and anisotropic phases have especially attractive properties in pharmaceutical technology. They are use as vehicle for different kind of drugs, especially those of topical application. Apart from that, many vegetable oil have pharmacological activity, increasing the necessity for the development of new delivery systems for them. We developed emulsions with vegetable oils at a fixed surfactant ratio and observed the formation of liquid crystalline phases. Nine vegetable oils: Andiroba, Apricot, Avocado, Brazil Nut, Buriti, Cupuassu, Marigold, Passion Fruit and Pequi and mineral oil were tested. Surfactant system was consisted by Steareth-2 and Ceteareth-5. Emulsions were prepared by the emulsion phase inversion (EPI) method, presenting high stability independent on the HLB value. Results indicate that this method could be employed to attain stable emulsions, even if the required HLB value is not known.

Relationship between Rheological Properties and One-Step W/O/W Multiple Emulsion Formation

Formation of a normal (not temporary) W/O/W multiple emulsion via the one-step method as a result of the simultaneous occurrence of catastrophic and transitional phase inversion processes has been recently reported. Critical features of this process include the emulsification temperature (corresponding to the ultralow surface tension point), the use of a specific nonionic surfactant blend and the surfactant blend/oil phase ratio, and the addition of the surfactant blend to the oil phase. The purpose of this study was to investigate physicochemical properties in an effort to gain a mechanistic understanding of the formation of these emulsions. Bulk, surface, and interfacial theological properties of adsorbed nonionic surfactant (CremophorRH40 and Span80) films were investigated under conditions known to affect W/O/W emulsion formation. Bulk viscosity results demonstrated that CremophorRH40 has a higher mobility in oil compared than in water, explaining the significance of the solvent phase. In addition, the bulk viscosity profile of aqueous solutions containing CremophorRH40 indicated a phase transition at around 78 +/- 2 degrees C, which is in agreement with cubic phase formation in the Winsor III region. The similarity in the interfacial elasticity values of CremophorRH40 and Span80 indicated that canola oil has a major effect on surface activity, showing the significance of vegetable oil. The highest interfacial shear elasticity and viscosity were observed when both surfactants were added to the oil phase, indicating the importance of the microstructural arrangement. CremophorRH40/Span80 complexes tended to desorb from the solution/solution interface with increasing temperature, indicating surfactant phase formation as is theoretically predicted in the Winsor III region. Together these interfacial and bulk rheology data demonstrate that one-step W/O/W emulsions form as a result of the simultaneous occurrence of phase-transition processes in the Winsor III region and explain the critical formulation and processing parameters necessary to achieve the formation of these normal W/O/W emulsions.

Topical Delivery of Lycopene Using Microemulsions: Enhanced Skin Penetration and Tissue Antioxidant Activity

Topical delivery of lycopene is a convenient way to supplement cutaneous levels of antioxidants. In this study, lycopene was incorporated (0.05%, w/w) in two microemulsions containing BRIJ-propylene glycol (2:1, w/w, surfactant blend) but different oil phases: mono/diglycerides of capric and caprylic acids (MG) or triglycerides of the same fatty acids (TG). Microemulsions containing MG and TG were isotropic, fluid, and clear, with internal phase diameters of 27 and 52 nm, respectively. Both MG- or TG-containing microemulsions markedly increased lycopene penetration in the stratum corneum, (6- and 3.6-fold, respectively) and in viable layers of porcine ear skin 2 (from undetected to 172.6 +/- 41.1 and 103.1 +/- 7.2 ng/cm(2), respectively) compared to a control solution. To assure that lycopene delivered to the skin was active, the antioxidant activity of skin treated with MG-containing microemulsion was determined by CUPRAC assay, and found to be 10-fold higher than untreated skin. The cytotoxicity of MG-containing microemulsion in cultured fibroblasts was similar to propylene glycol (considered safe) and significantly less than of sodium lauryl sulfate (a moderate-to-severe irritant) at 1-50 mu g/mL. These results demonstrate that the MG-containing microemulsion is an efficient and safe system to increase lycopene delivery to the skin and the antioxidant activity in the tissue. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:1346-1357, 2010

Photoprotective potential of emulsions formulated with Buriti oil (Mauritia flexuosa) against UV irradiation on keratinocytes and fibroblasts cell lines

Considering the belief that natural lipids are safer for topical applications and that carotenoids are able to protect cells against photooxidative damage, we have investigated whether topical creams and lotions, produced with Buriti oil and commercial surfactants, can exert photoprotective effect against UVA and UVB irradiation on keratinocytes and fibroblasts. Cell treatment was divided into two steps, prior and after exposition to 30 min of UVA plus UVB radiation or to 60 min of UVA radiation. Emulsions prepared with ethoxylated fatty alcohols as surfactants and containing alpha-tocopherol caused phototoxic damage to the cells, especially when applied prior to UV exposure. Damage reported was due to prooxidant activity and phototoxic effect of the surfactant. Emulsions prepared with Sorbitan Monooleate and PEG-40 castor oil and containing panthenol as active ingredient, were able to reduce the damages caused by radiation when compared to non-treated cells. When the two cell lines used in the study were compared, keratinocytes showed an increase in cell viability higher than fibroblasts. The Buriti oil emulsions could be considered potential vehicles to transport antioxidants precursors and also be used as adjuvant in sun protection, especially in after sun formulations. (C) 2009 Elsevier Ltd. All rights reserved.

Rheological behavior, zeta potential, and accelerated stability tests of Buriti oil (Mauritia flexuosa) emulsions containing lyotropic liquid crystals

Background: It is well known that the Amazon region presents a huge biodiversity; therefore, countless natural resources are being employed in the production of phytocosmetics and phytomedicines. Objective: The purpose of this work was to obtain emulsions produced with Buriti oil and nonionic surfactants. Methods: Two surfactant systems were employed (Steareth-2 associated to Ceteareth-5 and to Ceteareth-20) to produce the emulsions using phase diagram method. Emulsions were obtained by echo-planar imaging method at 75 degrees C. Rheological behavior and zeta potential were evaluated, and accelerated stability tests were performed. Results: All emulsions analyzed presented pseudoplastic behavior. Zeta potential values were obtained between -14.2 and -53.3 mV. The formulations did not show changes in either physical stability, pH, or rheological behavior after accelerated stability tests. Significant differences were observed only after temperature cycling test. Conclusion: Based on these results, the emulsions obtained could be considered as promising delivery systems.

Microemulsions Containing Medium-Chain Glycerides as Transdermal Delivery Systems for Hydrophilic and Hydrophobic Drugs

We evaluated the ability of microemulsions containing medium-chain glycerides as penetration enhancers to increase the transdermal delivery of lipophilic (progesterone) and hydrophilic (adenosine) model drugs as well as the effects of an increase in surfactant blend concentration on drug transdermal delivery. Microemulsions composed of polysorbate 80, medium-chain glycerides, and propylene glycol (1:1:1, w/w/w) as surfactant blend, myvacet oil as the oily phase, and water were developed. Two microemulsions containing different concentrations of surfactant blend but similar water/oil ratios were chosen; ME-lo contained a smaller concentration of surfactant than ME-hi (47:20:33 and 63:14:23 surfactant/oil/water, w/w/w). Although in vitro progesterone and adenosine release from ME-lo and ME-hi was similar, their transdermal delivery was differently affected. ME-lo significantly increased the flux of progesterone and adenosine delivered across porcine ear skin (4-fold or higher, p < 0.05) compared to progesterone solution in oil (0.05 +/- 0.01 mu g/cm(2)/h) or adenosine in water (no drug was detected in the receptor phase). The transdermal flux of adenosine, but not of progesterone, was further increased (2-fold) by ME-hi, suggesting that increases in surfactant concentration represent an interesting strategy to enhance transdermal delivery of hydrophilic, but not of lipophilic, compounds. The relative safety of the microemulsions was assessed in cultured fibroblasts. The cytotoxicity of ME-lo and ME-hi was significantly smaller than sodium lauryl sulfate (considered moderate-to-severe irritant) at same concentrations (up to 50 mu g/mL), but similar to propylene glycol (regarded as safe), suggesting the safety of these formulations.

Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity

The aim of this work was to investigate doxorubicin (DOX) percutaneous absorption and retention in the skin following iontophoresis. The convective flow contribution to the overall electrotransport of DOX was also elucidated for a non-ionic hyd roxyethylcellulose gel and a cationic chitosan gel. Moreover, the cytotoxicity of DOX and its formulations, with and without low electrical current, was verified. It was observed that iontophoresis of DOX significantly increased the skin permeation and retention of the drug. In addition, the electroosmotic flow was dramatically reduced when DOX was added to the non-ionic gel, thereby indicating that the drug interacted with negative charges in the skin. Interestingly, electroosmosis was also significantly reduced when the iontophoresis was performed in the presence of the chitosan gel, but in the absence of DOX. Consequently, the transport of an electroosmotic marker from this gel almost disappeared when the positively charged drug was added to the cationic gel. These results indicated that chitosan appeared to interact with negative charges in the skin. Hence, this carrier not only reduced electroosmotic flow, but also released DOX from ionic interactions with these sites and improved its diffusion to deeper skin layers. The application of the low electrical current directly to melanoma cells increased DOX cytotoxicity by nearly three-fold, which was probably due to membrane permeation. (c) 2008 Elsevier B.V. All rights reserved.

Myotoxic phospholipases A(2) isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: Cytotoxic effect on microorganism and tumor cells

This paper reports the purification and biochemical/pharmacological characterization of two myotoxic phospholipases A(2) (PLA(2)S) from Bothrops brazili venom, a native snake from Brazil. Both myotoxins (MTX-I and II) were purified by a single chromatographic step on a CM-Sepharose ion-exchange column up to a high purity level, showing M-r similar to 14,000 for the monomer and 28,000 Da for the dimer. The N-terminal and internal peptide amino acid sequences showed similarity with other myotoxic PLA2S from snake venoms, MTX-I belonging to Asp49 PLA(2) class, enzymatically active, and MTX-II to Lys49 PLA(2)S, catalytically inactive. Treatment of MTX-I with BPB and EDTA reduced drastically its PLA(2) and anticoagulant activities, corroborating the importance of residue His48 and Ca2+ ions for the enzymatic catalysis. Both PLA(2)S induced myotoxic activity and dose-time dependent edema similar to other isolated snake venom toxins from Bothrops and Crotalus genus. The results also demonstrated that MTXs and cationic synthetic peptides derived from their 115-129 C-terminal region displayed cytotoxic activity on human T-cell leukemia (JURKAT) lines and microbicidal effects against Escherichia coli, Candida albicans and Leishmania sp. Thus, these PLA(2) proteins and C-terminal synthetic peptides present multifunctional properties that might be of interest in the development of therapeutic strategies against parasites, bacteria and cancer. (C) 2008 Elsevier Inc. All rights reserved.

Antitumor effects of snake venom chemically modified Lys49 phospholipase A(2)-like BthTX-I and a synthetic peptide derived from its C-terminal region

The present work evaluates both in vitro and in vivo antitumor activity of BPB-modified BthTX-I and its cationic synthetic peptide derived from the 115-129 C-terminal region. BPB-BthTX-1 presented cytotoxicity of 10-40% on different tumor cell lines, which were also susceptible to the lytic action of the synthetic peptide. Injection of the modified protein or the peptide in mice, 5 days after transplantation of S 180 tumor cells, reduced 30 and 36% of the tumor size on day 14th and 76 and 79% on day 60th, respectively, when compared to the untreated control group. Thus, these antitumor properties might be of interest in the development of therapeutic strategies against cancer. (C) 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Hydrothermal Stability of Modified Silica Membranes for Gas Separation

A new class of hybrid molecular sieve silica (MSS) membranes is developed and tested against standard and organic templated membranes. The hybrid membrane is synthesized by the standard sol-gel process, integrating a template (methyltriethoxysilane - MTES) and a C6 surfactant (triethylhexylammonium bromide) into the silica film matrix. After hydro treatment under a relative humidity of 96% for 50h, the hybrid membrane shows no changes in its gas separation capabilities or energy of mobility. The structural characteristics and integrity of the hybrid membrane are retained due to a high concentration of organophilic functional groups and alkoxides observed using 29 Si NMR. In contrast, the structural integrity of the membranes prepared with non-templated films deteriorated during the hydro treatment due to a large percentage of silanol groups (Si-OH) which react with water. The hybrid membranes underwent a decrease in the H2/CO2 selectivity of only 1% whereas for the non-templated membrane a 21% decrease was observed. The transport mechanism of the hybrid membranes is activated as permeation increased with temperature. The activation energy for the permeation of H2 is positive while negative for CO2. The H2 permeation obtained was 3x 10 -8 mol.m -2 .s -1 .Pa -1 and permselectivities for H2/CO2 and H2/N2 varied between 1-7 and 31-34, respectively.

A review of the use of the basic cation saturation ratio and the "ideal" soil

The use of 'balanced' Ca, Mg, and K ratios, as prescribed by the basic cation saturation ratio (BCSR) concept, is still used by some private soil-testing laboratories for the interpretation of soil analytical data. This review aims to examine the suitability of the BCSR concept as a method for the interpretation of soil analytical data. According to the BCSR concept, maximum plant growth will be achieved only when the soil’s exchangeable Ca, Mg, and K concentrations are approximately 65 % Ca, 10 % Mg, and 5 % K (termed the ‘ideal soil’). This ‘ideal soil’ was originally proposed by Firman Bear and co-workers in New Jersey (USA) during the 1940s as a method of reducing luxury K uptake by alfalfa (Medicago sativa L.). At about the same time, William Albrecht, working in Missouri (USA), concluded through his own investigations that plants require a soil with a high Ca saturation for optimal growth. Whilst it now appears that several of Albrecht’s experiments were fundamentally flawed, the BCSR (‘balanced soil’) concept has been widely promoted, suggesting that the prescribed cationic ratios provide optimum chemical, physical, and biological soil properties. Our examination of data from numerous studies (particularly those of Albrecht and Bear, themselves) would suggest that, within the ranges commonly found in soils, the chemical, physical, and biological fertility of a soil is generally not influenced by the ratios of Ca, Mg, and K. The data do not support the claims of the BCSR, and continued promotion of the BCSR will result in the inefficient use of resources in agriculture and horticulture.

Observation of a cubic phase in mesoporous silicate films grown at the air/water interface

X-Ray diffraction is reported from mesoporous silicate films grown at the air/water interface. The films were studied both as powdered films, and oriented on silicon or mica sheets. At early stages of growth we observe Bragg diffraction from a highly ordered cubic phase, with both long and short d-spacing peaks. We have assigned this as a discontinuous micellar Pm3n phase in which the silica is partly ordered. Later films retain only the known hexagonal p6m peaks and have lost any order both at short d-spacings and the longer d-spacing Bragg peaks characteristic of the cubic structure. The silica framework is considerably expanded from that in bulk amorphous silica, average Si Si distances are some 30% greater. Incorporation of glycerol or polyethylene glycol preserves the earlier cubic structure. To be consistent with earlier, in situ, X-ray and neutron reflectivity data we infer that both structures are produced after a phase transition from a less-ordered him structure late in the induction phase. The structural relations between the film Pm3n and p6m phase(s) and the known bulk SBA-1 and MCM-41 phases are briefly discussed.

Synthesis of silica films at the air/water interface: Effect of template chain length and ionic strength

We have grown surfactant-templated silicate films at the air-water interface using n-alkyltrimethylammonium bromide and chloride in an acid synthesis with tetraethyl orthosilicate as the silicate source. The films have been grown with and without added salt (sodium chloride, sodium bromide) and with n-alkyl chain lengths from 12 to 18, the growth process being monitored by X-ray reflectometry. Glassy, hexagonal, and lamellar structures have been produced in ways that are predictable from the pure surfactant-water phase diagrams. The synthesis appears to proceed initially through an induction period characterized by the accumulation of silica-coated spherical micelles near the surface. All syntheses, except those involving C(12)TACl, show a sudden transformation of the spherical micellar phase to a hexagonal phase. This occurs when the gradually increasing ionic strength and/or changing ethanol concentration is sufficient to change the position of boundaries within the phase diagram. A possible mechanism for this to occur may be to induce a sphere to rod transition in the micellar structure. This transformation, as predicted from the surfactant-water phase diagram, can be induced by addition of salts and is slower for chloride than bromide counteranions. The hexagonal materials change in cell dimension as the chain length is changed in a way consistent with theoretical model predictions. All the materials have sufficiently flexible silica frameworks that phase interconversion is observed both from glassy to hexagonal and from hexagonal, to lamellar and vice versa in those surfactant systems where multiple phases are found to exist.

Polyinosinic acid and polycationic liposomes attenuate the hepatic clearance of circulating plasmid DNA

DNA that enters the circulation is rapidly cleared both by tissue uptake and by DNase-mediated degradation. In this study, we have examined the uptake of linear plasmid DNA in an isolated perfused liver model and following intra-arterial administration to rats. We found that the DNA was rapidly taken up by the isolated perfused liver without degradation. The single-pass extraction ratio was 0.76 +/- 0.05, the mean transit time was 15.3 +/- 3.6 s, and the volume of distribution was 0.29 +/- 0.07 ml/g. Hepatic uptake was saturable and was inhibited by polyinosinic acid or polycationic liposomes but not by condensation of the DNA with polylysine. When the linear plasmid DNA was administered in vivo, plasma half-life was 3.1 +/- 0.2 min, volume of distribution was 670 +/- 85 ml/kg, and clearance was 32 +/- 4 min. Coadministration of cationic liposomes decreased the volume of distribution to 180 +/- 28 ml/kg as well as the half-life (2.6 +/- 0.2 min). By contrast, polyinosinic acid significantly increased the circulating half-life (7.7 +/- 0.5 min), decreased the volume of distribution (95 +/- 17 ml/kg), and partially inhibited DNA degradation. When administered along with the liposomes and the polyinosinic acid, the distribution of plasmid-derived radioactivity decreased in the liver and increased in most other peripheral tissues. This study shows that pharmacological manipulation of the uptake and degradation of DNA can alter its distribution and clearance in vivo. These results may be useful in optimizing gene delivery procedures for in vivo gene therapy.