A study on the influence of emulsion droplet size on the skin penetration of tetracaine.

OBJECTIVES/AIMS: The influence of emulsion droplet size on the skin penetration of a model drug, tetracaine, was studied. For this purpose, in vitro dermal and transdermal delivery of tetracaine from 6 emulsions (3 macro-emulsions with droplet sizes >1 microm and 3 nano-emulsions with droplet sizes <100 nm) were tested. METHODS: Two approaches were used: in the first one, the composition of the emulsions was kept constant, while in the second one, the surfactant concentration in the aqueous phase was kept constant by varying the overall surfactant concentration. RESULTS: The results from emulsions differing only in droplet size did not provide statistically significant evidence for the anticipated increase in transdermal or dermal delivery (after 24 h) when reducing emulsion droplet size. The same results were obtained when the surfactant concentration in the aqueous phase was kept constant, indicating that there is no influence of emulsion droplet size on the skin penetration of tetracaine within the droplet size range studied. CONCLUSION: This is in contrast to what has been reported in various publications that claim penetration to increase with reducing droplet size. It should be noted that the results reported so far are based on emulsions that apart from droplet size also differed in composition and/or system components.

Polymeric surfactants based on inulin, a polysaccharide extracted from chicory. 1. Synthesis and interfacial properties.

Inulin, the polydisperse reserve polysaccharide from chicory, has been modified by carbamoylation in organic solvents. The reaction of inulin with a range of alkyl isocyanates resulted, after crystalization, in a variety of carbamoylated inulins from which the interfacial properties were determined. The medium and long chain carbamoylated inulins showed a good to very good reduction of the interfacial tension which makes these biopolymers interesting in the field of biodegradable surface active agents.

Influence of surface coverage with poly(ethylene oxide) on attachment of sterically stabilized microspheres to rat Kupffer cells in vitro.

The attachment to rat Kupffer cells of polymeric microspheres, sterically stabilized with different amounts of pendant poly(ethylene oxide) (PEO), was assessed in vitro. Four types of copolymer polystyrene (PS) microspheres were synthesized by variation of four possible monomer ratios that included styrene, methoxy-PEO-methacrylate (750 and 2000 mol. wt PEO) and allylurea. This produced poly(styrene-(methoxy-PEO)methacrylate) microspheres with hydrophilic side-groups of either urea (PS-U-PEO) and/or mixed molecular weight (750/2000 mol. wt) PEO (PS-U-M-PEO, PS-M-PEO), or single molecular weight (2000) PEO (PS-PEO) at their surfaces. The hypothesis was tested that increasing the total content of PEO comprising the steric barrier reduces attachment to cell surfaces. Attachment of PEO microspheres bearing the urea spacer and/or mixed molecular weight PEO was found to be intermediate between charge stabilized control PS and PEO (2000 mol. wt) bearing particles. Post-adsorption of different Poloxamer (PEO-poly(propylene oxide)-PEO) surfactants to the microspheres further decreased attachment. Significant negative linear correlations between surface PEO content, measured by electron spectroscopy for chemical analysis (ESCA), and attachment to Kupffer cells were demonstrated. Decreases in attachment also resulted with all graft PEO particles bearing adsorbed sodium dodecyl sulphate (SDS), whilst the attachment of SDS-treated PS control particles increased. It is proposed that trains of adsorbed graft PEO are displaced by the SDS to increase the effective fraction of graft PEO within the steric layer. Overall, increasing the amount of hydrophilic PEO in the steric layer, from graft and adsorbed sources, reduces the attachment of these particles to Kupffer cells in vitro.

Surface modification of poly(lactide-co-glycolide) nanospheres by biodegradable poly(lactide)-poly(ethylene glycol) copolymers.

The modification of surface properties of biodegradable poly(lactide-co- glycolide) (PLGA) and model polystyrene nanospheres by poly(lactide)-poly(ethylene glycol) (PLA:PEG) copolymers has been assessed using a range of in vitro characterization methods followed by in vivo studies of the nanospheres biodistribution after intravenous injection into rats. Coating polymers with PLA:PEG ratio of 2:5 and 3:4 (PEG chains of 5000 and 2000 Da. respectively) were studied. The results reveal the formation of a PLA:PEG coating layer on the particle surface resulting in an increase in the surface hydrophilicity and decrease in the surface charge of the nanospheres. The effects of addition of electrolyte and changes in pH on stability of the nanosphere dispersions confirm that uncoated particles are electrostatically stabilized, while in the presence of the copolymers, steric repulsions are responsible for the stability. The PLA:PEG coating also prevented albumin adsorption onto the colloid surface. The evidence that this effect was observed for the PLA:PEG 3:4 coated nanospheres may indicate that a poly(ethylene glycol) chain of 2000 Da can provide an effective repulsive barrier to albumin adsorption. The in vivo results reveal that coating of PLGA nanospheres with PLA:PEG copolymers can alter the biodistribution in comparison to uncoated PLGA nanospheres. Coating of the model polystyrene nanospheres with PLA:PEG copolymers resulted in an initial high circulation level, but after 3 hours the organ deposition data showed values similar to uncoated polystyrene spheres. The difference in the biological behaviour of coated PLGA and polystyrene nanospheres may suggest a different stability of the adsorbed layers on these two systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Future developments in cosmetic formulations.

Synopsis In recent years, there have been a great deal of interest in applications of microemulsions, liposomes (vesicles) and multiple emulsions in cosmetic formulations. These systems will provide the cosmetic industry with new types of formulations which are easier to apply, better functional benefit and potentially safer formulations. Microemulsions are thermodynamically stable systems and hence shelf life is no problem. Many cosmetic ingredients can be adequately solubilized in the swollen micelles of the microemulsions. Such solubilized systems may enhance transport and diffusion through various barriers, eg., the skin, thus enhancing the efficacy of the formulations. However, microemulsions may cause skin irritation by disrupting the liquid crystalline structure of the stratum corneum. This problem may be overcome by formulating microemulsions, which on evaporation produce lamellar liquid crystalline structures. The problem of skin irritation is certainly reduced or eliminated using liposomes or vesicles, which offer an alternative to microemulsions. The principles for formation and stabilization of vesicles are discussed in this paper and research work is needed to produce nanocapsules from liposomes, using polymerizable surfactants. Multiple emulsions of the water/oil/water (w/o/w) or oil/water/oil (o/w/o) types are also valuable systems for formulating cosmetics. In the first place, they offer a means of sustained release of the various ingredients. Secondly, they allow one to separate the various ingredients in the formulation, thus preventing their possible interaction. The basic principles required for preparation of stable multiple emulsions are summarised. Developments of polymeric surfactants led to the formulation of stable multiple emulsions. An example of a recently formulated stable w/o/w multiple emulsion is given in this paper The stability of the system was investigated using optical microscopy. Creaming occurred on storage, particularly at high temperature (40 degrees C) and this was significantly reduced by addition of Kelzan (a polysaccharide with high molecular weight). The final formulation was studied rheological techniques.

Steric stabilization of microspheres with grafted polyethylene oxide reduces phagocytosis by rat Kupffer cells in vitro.

Sterically stabilized polyethylene oxide-polystyrene copolymer microspheres, (PS-PEO) and charge stabilized polystyrene (PS) microspheres of similar size (1 micron) were prepared in order to compare their uptake by cultured rat Kupffer cells isolated by centrifugal elutriation. The uptake of the sterically stabilized particles was found to be much less than that for the charge stabilized control. The uptake of microspheres stabilized with covalently grafted PEO was lower or equivalent to that of control microspheres stabilized by the adsorption of the non-ionic PEO-polypropylene oxide (PPO-PEO) surfactant Poloxamer 238 or Methoxy-PEO. Phagocytic uptake by Kupffer cells at low and body temperature (8 degrees C and 37 degrees C) demonstrated that PS-PEO particles showed both low adherence and low metabolic uptake. The adsorption of PEO, as Poloxamer 238, to particles with covalently attached or grafted PEO resulted in a synergistic reduction in uptake that was greater than the individual effects of grafting and adsorption alone (P less than or equal to 0.001). It is suggested that this combination produces a more effective steric barrier on the particle surface with the Poloxamer adsorbing to the surface between the grafted PEO chains. The relevance to drug targeting/carrier systems is discussed.