Structural changes of biocompatible neutral microemulsions stabilized by mixed surfactant containing soya phosphatidylcholine and their relationship with doxorubicin release.

Depending on the composition, the mixture of surfactant, oil and water, may form supramolecular aggregates with different structures which can significantly influence the drug release. In this work several microemulsion (ME) systems containing soya phosphatidylcholine (SPC) and eumulgin HRE40 (EU) as surfactant, cholesterol (O) as oil phase, and ultra-pure water as an aqueous phase were studied. MEs with and without the antitumoral drug doxorubicin (DOX) were prepared. The microstructures of the systems were characterized by photon correlation spectroscopy, rheological behavior, polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD). The results reveal that the diameter of the oil droplets was dependent on the surfactant (S) amount added to formulations. The apparent viscosity was dependent on the O/S ratio. High O/S ratio leads to the crystallization of cholesterol polymorphs phases which restricts the mobility of the DOX molecules into the ME structure. Droplets with short-range spatial correlation were formed from the ME with the low O/S ratio. The increase of the cholesterol fraction in the O/S mixture leads to the formation of ordered structures with lamellar arrangements. These different structural organizations directly influenced the drug release profiles. The in vitro release assay showed that the increase of the O/S ratio in the formulations inhibited the constant rate of DOX release. Since the DOX release ratio was directly dependent on the ratio of O/S following an exponential decay profile, this feature can be used to control the DOX release from the ME formulations.

Oil-in-water lecithin-based microemulsions as a potential delivery system for amphotericin B.

In this work the structural features of microemulsions (MEs) containing the pharmaceutical biocompatible Soya phosphatidylcholine/Tween 20 (1:1) as surfactant (S), Captex 200 as oil phase (O), and phosphate buffer 10mM, pH 7.2 as aqueous phase (W) were studied. Systems obtained with different proportions of the components were described by pseudo-ternary phase diagrams in order to characterize the microemulsions studied here. MEs were prepared with and without the polyene antifungal drug amphotericin B (AmB). The maximum AmB incorporation into the ME system was dependent on both the oil phase and surfactant proportions with 6.80 and 5.7 mg/mL in high contents, respectively. The incorporation of AmB into the ME systems significantly increased the profile of the droplet size of the ME for all ranges of surfactant proportions used in the formulations. The microstructures of the system were characterized by dynamic light scattering (DLS) and rheological behavior. The DLS results showed that the size of the oil droplets increases 4.6-fold when AmB is incorporated into the ME system. In all cases the increase in the proportion of the oil phase of the ME leads to a slight increase in the diameter of the oil droplets of the system. Furthermore, for both the AmB-loaded and AmB-unloaded MEs, the size of the oil droplets decrease significantly with the increase of the S proportion in the formulations, demonstrating the efficiency of the surfactant in stabilizing the ME. Depending on the ME composition, an anti-thixotropic behavior was found. The maximum increases of the consistency index caused by the increase of the oil phase of the ME were of 17- and 25-times for the drug-loaded and drug-unloaded MEs, respectively. However, the observed effect for the drug-loaded ME was about 4.6 times higher than that for the drug-unloaded one, demonstrating the strong effect of the drug on the rheological characteristics of the ME system. Therefore, it is possible to conclude that the investigated ME can be used as a very promising vehicle for AmB.

Relationship between structural features and in vitro release of doxorubicin from biocompatible anionic microemulsion.

In this work structural features of anionic microemulsions, containing the pharmaceutical biocompatible components soya phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as surfactant, cholesterol (CHO) as oil phase and aqueous buffer were studied. Microemulsions were formulated with and without the antitumor drug doxorubicin (DOX). The various microstructures characterized in the pseudo-ternary phase diagram were analyzed by polarized light microscopy, small-angle X-ray scattering (SAXS) and X-ray diffraction (XRD) as well as by their ability to incorporate and release DOX. The experimental results demonstrated a correlation between the composition, the structural features and drug delivery. It was found that at higher cholesterol contents, the crystallization of CHO polymorph phases changed the mobility of DOX molecules. Droplets were formed with short-range spatial correlation from a microemulsion (ME) with a low surfactant:oil ratio. More ordered structures with lamellar arrangements formed by the increasing of the CHO proportions in the formulation may be due to CHO crystallization. The in vitro release of DOX showed that the presence of a high content of crystalline CHO prolongs the release of DOX from ME. The retention of DOX in the internal oil phase of the ME may modulate the drug release for a prolonged time. These results clearly demonstrate the potential of ME as a drug-delivery system.

Ureasil-polyether hybrid film-forming materials.

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules.

Structural characterization and in vivo evaluation of retinyl palmitate in non-ionic lamellar liquid crystalline system.

Carrier systems for lipophilic drugs, such as the liquid crystalline systems (LCS) have been extensively studied to improve effect and selectivity. Retinyl palmitate (RP) is widely used in pharmaceutical and cosmetics products to improve the skin elasticity. The aim of this study was the development, characterization and the in vivo effectiveness of RP in non-ionic LCS structures. LCS containing polyether functional siloxane as oil phase, silicon glycol copolymer as surfactant and water in the ratio 30:10:60, with and without RP were studied. The results of the polarized light microscopy, small-angle X-ray scattering and rheology analysis indicated the presence of typical LCS structures with lamellar arrangement. Regardless of the presence of RP, the rheological studies showed the pseudo plastic behavior of the systems. However, highest hysteresis area was verified when comparing the system in the presence and in the absence of RP. Stability study SAXS monitored, carried out up to 30 days in various storage temperature conditions (25±2 °C, 37±2 °C and 5±2 °C) demonstrated the great structural stability of the LCS systems. The in vivo effectiveness analysis suggests that the RP-loaded LCS provided a significant reduction of the orbicular wrinkles in human volunteers (P=0.048).

Structure and viscoelastic behavior of pharmaceutical biocompatible anionic microemulsions containing the antitumoral drug compound doxorubicin.

Structure and viscoelastic properties of negatively charged oil-in-water (o/w) microemulsions have been investigated. Microemulsions (ME) containing soya phosphatidylcholine (SPC), eumulgin HRE 40 (EU) and sodium oleate (SO) as surfactant, cholesterol (CHO) as oil phase, and aqueous buffer with and without the antitumoral doxorubicin (DOX) have been studied. The effect of the oil phase/surfactant ratio (O/S) and the DOX incorporation on the structural and rheological properties have been studied in several compositions of ME systems. The rheological analyses were performed through the oscillation stress sweep, creep recovery test, and viscosity test. The combination of the DOX incorporation with the high O/S ratio provided a further viscoelastic structure with linear behavior. Independently of the O/S ratio the oil phase diameter increases according to a sigmoid profile, stabilizing up to 340 min. The apparent viscosity decreases a minimum value with the shear rate, but increases with both the O/S ratio and the DOX incorporation in the system. The structural and rheological properties of the studied MEs were directly dependent on the O/S ratio and can be used to improve the application of the system in the pharmaceutical field.