Monoolein Water Research Articles

Monoolein liquid crystalline phases for topical delivery of crocetin.

The present investigation concerns the production and characterization of monoolein-water systems designed for cutaneous administration of crocetin. The different monoolein crystalline phases forming in the presence of crocetin as a function of added water have been investigated by x-ray and polarized light microscopy. Franz cell was employed to compare in vitro the crocetin diffusion from selected monoolein water systems containing 95, 90 or 75% w/w of monoolein, while to investigate the performance of monoolein-water as transdermal delivery systems, in vivo studies, based on tape stripping were performed. The presence of micellar, lamellar and Q230 phases was found in the case of systems containing monoolein 95, 90 and 75% w/w respectively, with a viscosity almost directly proportional to the amount of added water. The higher the amount of water, the longer the crocetin stability, while its diffusion was slower in the case of more viscous systems. Tape stripping results indicated a more rapid depletion of crocetin on stratum corneum in the case of systems characterized by cubic phases, followed by micellar and lamellar ones. This behaviour could be related to a more rapid drug penetration throughout the deeper skin strata.

Ciprofloxacin monoolein water gels as implants for the treatment of chronic osteomyelitis: In vitro characterization.

This work investigated the possibility of using the biodegradable gentamicin-monoolein-water gels as models, in order to obtain a similar sustained release of ciprofloxacin hydrochloride. Four gels containing antibiotics were prepared and were examined with regard to their physicochemical properties and in vitro drug release characteristics. Ciprofloxacin, unlike gentamicin, which was dissolved in the matrix, was in dispersed form. However, despite its insolubility, microscopic observation, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction showed that the developed gel was in the cubic liquid crystalline structure and have maintained their ability to progressively release ciprofloxacin. ciprofloxacin-monoolein-water (5:80:15% w/w), which released in vitro approximately 85% of ciprofloxacin after 16 days could possibly be considered as an alternative to a gentamicin-monoolein-water gel for the treatment of chronic osteomyelitis.

Development of an in vitro Endotoxin Test for Monoolein–Water Liquid Crystalline Gel for Use as an Implant

Purpose: Drugs that are administered by parenteral route must be apyrogenic. The aim of this study was to develop an in vitro endotoxin test for liquid crystalline gels for use as implants, using a monoolein–water liquid crystalline gel as a model. Methods: The gel-clot technique was used. The gel was dissolved first in isopropyl myristate, and the endotoxins were extracted with water for bacterial endotoxin test. Tests for the labelled lysate sensitivity and interfering factors were performed to validate the developed method. The limit of detection of endotoxin in the gel was also determined. Results: The labelled lysate sensitivity was confirmed. It was not influenced by the presence of extracts from the gels. Endotoxins in the contaminated test gels were completely extracted. Endotoxin concentration in the tested gels was below the calculated threshold endotoxin level. Conclusion: A method to perform in vitro endotoxins test of liquid crystalline gels was successfully developed and validated. Application of the technique to gels currently being developed in our laboratories indicate that the gels were apyrogenic.Keywords: In vitro bacterial endotoxin test; liquid crystalline gels; test validation; monoolein–water.

Interaction of Cytochrome-C with Monoolein Liquid Crystals Mesophases

Phase behaviour and structural properties of monoacylglycerides in water have been investigated for a long time, due to their extended polymorphism. In particular, monoolein (MO) in water shows several mesophases, characterized by a high disordered conformation of the hydrocarbon chains. At such conditions, an embedded protein can influence the physical properties of the lipid matrix, depending on the protein size and polarity. We take advantage of the structural properties of monoolein and cytochrome-c to extensively study the temperature effects on the cubic transition from Pn3m to Im3m by means of small-angle X-ray scattering technique (SAXS) and electronic absorption spectroscopy (EAS). To do so, we made samples composed of monoolein (50 mg/ml) in the presence of 1, 10 and 50 mg/ml of cytochrome-c. Ours preliminary SAXS results indicate that cyto-c is able to change the monoolein water channels, from cubic Pn3m to Im3m. Moreover, such kinetic behaviour is too slow, taking place within some days. EAS measurements indicate that the incorporation of cyto-c within the Monoolein water channels begins after two or three days (after the sample preparation). Besides, after one week of sample preparation the amount of cyto-c within the Monoolein water channels is equal to 60% and 34% for 1 and 10 mg/ml of cyto-c, respectively. Interestingly, increasing the temperature, the unity cell parameter decreases, indicating that water is going out from the unity cell and the symmetry of the liquid crystal phase can changes to another cubic or to hexagonal, depending on the temperature and the sample composition. We believe that these results could bring more insights on the protein-liquid crystal interaction.

Monoolein–Water Liquid Crystalline Gels of Gentamicin as Bioresorbable Implants for the Local Treatment of Chronic Osteomyelitis: In Vitro Characterization

To maximize the efficacy of chronic osteomyelitis antibiotherapy while reducing antibiotic systemic toxicity, as well as time and costs of hospitalizations, it has been thought that monoolein–water gels incorporating gentamicin sulfate could be used as local, bioresorbable, and sustained-release implants. For this purpose, four formulations were examined with regard to their physicochemical and in vitro drug release characteristics. Hot stage microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and X-ray diffraction showed cubic liquid crystalline and eutectic structures. The more suitable formulation consisting of 80–15–5% wt/wt monoolein–water–gentamicin sulfate progressively released the antibiotic for a period of 3 weeks without burst effect. Moreover, the content and the release profile of gentamicin sulfate were not significantly changed after storage at 2–6°C for a period of 10 months.

Molecular recognition and controlled release in drug delivery systems based onnanostructured lipid surfactants

Several monoolein/water (MO/W) based liquid crystalline (LC) nanostructuredmesophases have been revisited in view of the new trends of modern drug deliveryformulations. The shape and amphiphilic character of the investigated lipid moleculesaddress the preferential polar–apolar interfacial curvature and the delicate interplay ofdifferent intermolecular forces that drive self-assembly and thermodynamic stability of thenanostructures.Here some preliminary results related to the release of the antiviral drug 1-amine-adamantanehydrochloride, solubilized in the aqueous domain of bicontinuous cubic and reversehexagonal LC phases, suggest these MO based LC phases as possible nano-depot systemsfor long term controlled release. Drug release was followed by conductivity measurementsduring a period of ten days.An effective and targeted drug delivery often requires a specific molecular recognition.With this aim, the possibility to entrap suitable molecules such as lauroylcholine (LCh, acationic surfactant having a peptide-like polar head that can ‘recognize’ membraneproteins) and adenosine monophosphate disodium salt (NaAMP, an electrolyte that can‘recognize’ purine receptors) has been tested. The addition of LCh to MO/W cubic gyroid(CG) LCphase causes a cubic–lamellar phase transition. The addition of NaAMP still allows the formation ofthe CG nanostructure. In the presence of both NaAMP and LCh again aCG LC phase forms.The bicontinuous CG LC phases have been characterized by NMR and SAXS.

Phase behavior of the monoolein–water system: The effects of addition of the hydrocarbon 1,8-cineole and supercritical carbon dioxide

The results of a study on the phase behavior of the monoolein/water system with the addition of the hydrocarbon 1,8-cineole (C 10H 18O) and supercritical carbon dioxide at 15 MPa is presented. To two mixtures consisting of 9 and 18 wt.% water in monoolein, 5, 10, and 20 wt.% cineole were added and heated to between 35 and 80 °C at atmospheric pressure and in the presence of supercritical carbon dioxide. The phase changes were followed by deuterium nuclear magnetic resonance ( 2 H NMR), light microscopy, and ocular inspection. The mesomorphic structures developed in the 9 wt.% water sample suffered little change due to the presence of the supercritical carbon dioxide. However, in the mixture with 18 wt.% water, the native phase structures were dramatically affected and an isotropic fluid phase developed. The addition of cineole has lowered the LC-L α→LC-H II phase transition in the samples with 9 and 18 wt.% water in monoolein. The surplus of supercritical carbon dioxide in the samples has resulted in similar developments. Regardless of the amount of cineole present in the system, only the isotropic fluid phase was observed in the samples with 18 wt.% water in monoolein.

Liquid crystalline properties and extractability of monoolein–water systems by supercritical carbon dioxide

The influence of phase structure on the extraction recovery of monoolein from monoolein–water systems by supercritical carbon dioxide was investigated. Two monoolein–water mixtures at concentrations of 9 wt% water and 18 wt% water, respectively, were studied. 2 H-NMR was used to monitor changes of the phase structures in supercritical conditions. The results showed that the phase structure and the water–monoolein interactions play a role on the extraction yield. The monoolein recovery was higher in the 9 wt% water sample in which L α phase was present compared to the 18 wt% water sample in which the L α melted to yield a L 2 phase. When the phase structures were the same in both samples, the extraction recovery was determined by the solubility properties of the components of the system. The changes due to the presence of supercritical carbon dioxide were shown also to depend on the water concentration of the monoolein–water mixture besides the temperature. The 18 wt% mixture showed a L 2 phase structure in all the range of the temperature investigated while the 9 wt% water mixture showed phase changes from L α phase to L 2 phase in the same temperature range.

Dry powder precursors of cubic liquid crystalline nanoparticles (cubosomes

Cubosomes are dispersed nanostructured particles of cubic phase liquid crystal that have stimulated significant research interest because of their potential for application in controlled-release and drug delivery. Despite the interest, cubosomes can be difficult to fabricate and stabilize with current methods. Most of the current work is limited to liquid phase processes involving high shear dispersion of bulk cubic liquid crystalline material into sub-micron particles, limiting application flexibility. In this work, two types of dry powder cubosome precursors are produced by spray-drying: (1) starch-encapsulated monoolein is produced by spray-drying a dispersion of cubic liquid crystalline particles in an aqueous starch solution and (2) dextran-encapsulated monoolein is produced by spray-drying an emulsion formed by the ethanol–dextran–monoolein–water system. The encapsulants are used to decrease powder cohesion during drying and to act as a soluble colloidal stabilizer upon hydration of the powders. Both powders are shown to form (on average) 0.6 μm colloidally-stable cubosomes upon addition to water. However, the starch powders have a broader particle size distribution than the dextran powders because of the relative ease of spraying emulsions versus dispersions. The developed processes enable the production of nanostructured cubosomes by end-users rather than just specialized researchers and allow tailoring of the surface state of the cubosomes for broader application.

Addition of hydrophilic and lipophilic compounds of biological relevance to the monoolein/water system. I. Phase behavior

The solubilization of hydrophilic and lipophilic molecules, with biological relevance, in the monoolein/water (MO/W) system has been investigated for phase behavior. Small angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) and optical microscopy (OM) have been used to characterize the microstructure of the liquid crystalline phases. Partial phase diagrams of the MO/W system in the presence of sodium decanoate, 1-adamantanamine hydrochloride, decanoic and dodecanoic acids, acetyl salicilic acid and retinol have been determined. The stability of the various phases has been followed for at least eight months. The polarity and the molecular structure of the additive determine whether it is located at the polar interface or in the apolar region of the lipid layer. Therefore, the additive affects the interfacial curvature of the lipid layer differently, which in turn will trigger transition to disparate phases. A cubic-to-reverse hexagonal phase transition has been observed with time for most of the ternary systems, with the exception of 1-adamantanamine hydrochloride and retinol. The release of free glycerol and oleic acid due to MO hydrolysis has been clearly demonstrated by 13C NMR. This would account for the changes in phase behavior observed with time. The released oleic acid, located in the MO acyl chain region, favors the inverse interfacial curvature. The average lipid dimensions in the cubic and in the reverse hexagonal phases have been calculated from SAXS data.

Structure of water confined in bicontinuous cubic lipid–water mesophases

The first wide-angle neutron diffraction studies of the structure of water confined in bicontinuous cubic lipid–water mesophases are presented. By applying H–D substitution to the water component, the partial pair correlation functions gHH(r), gXH(r) and gXX(r) could be calculated from the measured total structure factors, where H and X denote the substituted and non-substituted atoms of the samples, respectively. Experiments were performed for two systems differing in lipid configuration, water fraction and temperature: monoolein–water (35% w/w, 35 °C) and monoelaidin–water (40% w/w, 50 °C). The conditions of hydration and temperature were chosen in order to obtain the cubic QIIG phase in both systems and to tune the water channel thickness. There is no evidence to suggest that the nature of the inter-bilayer water is substantially altered by interfacial interactions or to support the concept of structured water with correlations extending up to several tens of angstroms. Small but pronounced modifications of the HH and XH pair correlation functions are observed for both lipid systems as compared with bulk water. These modifications may be interpreted as a slight increase in the intermolecular distances in water due to confinement.

Identification of thermotropic phase transitions of glyceryl monoolein–water systems by low frequency dielectric spectroscopy

Thermotropic phase transitions of glyceryl monoolein–water systems have been investigated using dielectric spectroscopy over a frequency range of 10 −2–10 6 Hz and a temperature range of 15–100°C, and also using differential interference contrast (DIC) microscopy fitted with a hot stage as a support technique. The frequency and temperature dependencies of the dielectric permittivity of systems undergoing transitions between lamellar, cubic, reverse hexagonal and L 2 phases are reported. It was demonstrated that the frequency dependent response is highly sensitive to changes in phase and a model is described which allows the dielectric behaviour to be interpreted in terms of an equivalent circuit diagram, thereby allowing the response to be related to specific structural features within the sample. Similarly, it was demonstrated that the phase transition temperatures and ranges could be identified using the dielectric technique, yielding results which were in good agreement with those obtained using DIC microscopy for those systems whereby the phase changes are optically identifiable. The study therefore suggests that low frequency dielectric analysis is a potentially highly useful tool for the identification of thermotropic phase changes.

Two cubic phases in monoolein–water system

Two cubic phases in monoolein–water system

The visualization of a lamellar and a cubic mesophase in the monoolein—water system by freeze-etching

The visualization of a lamellar and a cubic mesophase in the monoolein—water system by freeze-etching