Kinetic and thermodynamic of lactoferrin - Ethoxylated-nonionic surfactants supramolecular complex formation.

Understanding nonionic surfactant-protein interactions is fundamental from both technological and scientific points of view. However, there is a complete absence of kinetic data for such interactions. We employed surface plasmon resonance (SPR) to determine the kinetic and thermodynamic parameters of bovine lactoferrin-Brij58 interactions at various temperatures under physiological conditions (pH 7.4). The adsorption process was accelerated with increasing temperature, while the desorption rate decreased, resulting in a more thermodynamically stable complex. The kinetic energetic parameters obtained for the formation of the activated complex, [bLF-Brij58]‡, indicated that the potential energy barrier for [bLF-Brij58]‡ formation arises primarily from the reduction in system entropy. [bLF-Brij58]○ formation was entropically driven, indicating that hydrophobic interactions play a fundamental role in bLF interactions with Brij58.

Design of oriented mesoporous silica films for guiding protein adsorption states.

The highly-oriented cylindrical mesoporous silica films were synthesized on the rubbing-treated polyimide by adjusting the molar ratio of the orientation-directing agent (Brij56) to the structure-directing agent (P123) as surfactants in the silica precursor solutions for guiding protein adsorption states. As a result, the diameter and the orientation degree of mesopores changed with the molar ratio of Brij56 to P123. The maximum orientation degree (93%) of cylindrical mesopores oriented in the direction perpendicular to the rubbing direction was observed when the molar ratio of Brij56 to P123 was 3. Then, the dissolution features in simulated body fluid and the protein adsorption properties of the oriented cylindrical mesoporous silica films were investigated. The silica skeletons were gradually dissolved from the upper film surfaces and subsequently, the mesopore structures were collapsed when the films were immersed for 90 min. Moreover, the protein adsorption amount and the ratio from the mono-component and two-component solutions on the films were higher than those on the unoriented cylindrical mesoporous silica films due to the formation of open-ended cylindrical mesopore shapes and sizes. In addition, the shapes of the proteins adsorbed on the films had anisotropy, which would be reflected by the cylindrical mesopore shapes generated by the dissolution of silica layers and subsequent exposure of inner mesopore surfaces. Therefore, the synthesized highly-oriented cylindrical mesoporous silica films were useful to adsorb mesoscale biomolecules such as proteins and can effectively guide their anisotropic adsorption shapes, and therefore have the potential to be used as surface-coating films of polyimide in biomedical fields.

Brij-58, a potential injectable protein-stabilizer used in therapeutic protein formulation.

Polysorbates (PSs) are common protein stabilizers used in biotherapeutic formulations. However, PSs are heterogeneous and unstable in liquid protein formulations [1,2]. The purpose of this work is to explore possible alternatives for polysorbate replacements that demonstrate superior protein protection, superior self-stability, low toxicity, and wide applicability. For this purpose, 8 non-ionic surfactants that have not yet been used as excipients in marketed biotherapeutic products were investigated with PS20/80 as the benchmark. Compared with PS20/80, Brij-58 showed better protein protection ability in the mAb1 formulation under forced degradation conditions when examined by visual inspection, SEC, and dynamic lighting scanning. Additionally, Brij-58 has a better inherent stability than PS20/80 in the protein formulation when detected by UPLC-CAD. Moreover, Brij-58 is an inert excipient that does not affect protein bioactivity and conformation. In addition, the LD50 and hemolysis concentration of Brij-58 were determined, which is relatively safe when used as a parenteral injection. Furthermore, Brij-58 was also an effective protein stabilizer for the other two antibody products (IgG4 subtype and bispecific antibody) in the shaking study. In summary, Brij-58 stands out as a promising PS replacement in biotherapeutic formulations with a safe, stable and effective protein-protection profile among candidate surfactants.

A road to bring Brij52 back to attention: Shear stress sensitive Brij52 niosomal carriers for targeted drug delivery to obstructed blood vessels.

Thrombosis is a shared perpetrating event in the pathophysiology of several cardiovascular disorders such as ischemic stroke, venous thromboembolism, atherosclerosis, and myocardial infarction. Despite holding a wide range of ammunition in our arsenal to ameliorate such conditions, we are still facing with many stumbling blocks in the satisfactory pharmacotherapy of cardiovascular diseases among which the risk of hemorrhage and life threatening drug interactions can be highlighted. Our hypothesis focuses on mimicking the nature of platelet activation, to design a novel targeted delivery system based on the alterations of a physical parameter, the hemodynamic shear stress, to aim at the offending thrombi in an attempt to offer a noninvasive, rapid, and monitoring-free method that not only can prolong the circulation time of the cargo, but also deliver it locally and reduce both the undesirable adverse effects and drug interactions. Brij52 is our chosen candidate due to its unique non-spherical morphology after forming a niosomal vesicle. We surmised that thanks to its non-spherical shape, diverse shear rates may generate different shear stresses to its equators and axes which might result in the breakdown or at least distortion of niosomal structure under elevated shear stress. The vesicles have to be synthesized in the size of platelets or in the nano-sized scale. In order to prolong the time vesicles are circulating in the blood, PEGylation may help and to make such carriers highly selective to be only activated during pathophysiological clot formation, attachment of domain A1 von Willebrand factor can be of benefit to lead this proposed delivery system to the site of thrombus formation where shear rate exceeds those of 1000 s-1. There is now an emerging fast growing universal research on shear activated carriers, and the present theory is an endeavor to reach a successful treatment strategy to combat cardiovascular diseases based on the hypothesis that a non-spherical nano-carrier such as Brij 52 niosomal vesicle can be of paramount benefit to deliver current antithrombotic agents in a targeted and controlled manner in the presence of elevated shear stress of the obstructed blood vessels. With more radical advanced drug delivery systems being developed and new strategies being pursued, there will be more options in our arsenal to represent a promising avenue for achieving preventive, well-tolerated, and intelligent drug carriers to circumvent the drawbacks of antithrombotic pharmacotherapy.

Molecular features of nonionic detergents involved in the binding kinetics and solubilization efficiency, as studied in model (Langmuir films) and biological (Erythrocytes) membranes.

The effect of the nonionic detergents Brij-98 and Brij-58 over human erythrocytes was studied through quantitative hemolysis and in Langmuir films. Hemolytic tests revealed that Brijs are stronger membrane solubilizers than Triton X-100 (TX-100), with effective detergent/lipid ratios of 0.18 and 0.37 for Brij-98 and Brij-58, respectively. Experiments with Langmuir films provided significant information on the kinetics and thermodynamics of detergent-membrane interaction. The adsorption (ka) and desorption (kd) rate constants of Brijs were lower than those of TX-100. In the case of ka, that is probably due to their larger hydrophilic head (with twice (20) the oxyethylene units of TX-100). As for the thermodynamic binding constant, the linear and longer hydrophobic acyl chains of Brijs favor their stabilization in-between the lipids, through London van der Waals forces. Consequently, Kb,m values of Brij-98 (12,500 M-1) and Brij-58 (19,300 M-1) resulted higher than TX-100 (7500 M-1), in agreement with results from the hemolytic tests. Furthermore, Brij-58 binds with higher affinity than Brij-98 to bilayers and monolayers, despite its shorter (palmitic) hydrocarbon chain, showing that unsaturation restrains the detergent insertion into these environments. Our results provide significant information about the mechanism of interaction between Brijs and membranes, supporting their distinct solubilization effect.

Study of Cationic and Nonionic Mixed Micelles with NaBr and 3,5-Cl2C6H3CO2Na by Use of Probe Nucleophilic Reaction of Piperidine with Ionized Phenyl Salicylate.

Behaviors of cationic and nonionic mixed micelles in the form of hexadecyltrimethylammonium bromide (HDABr) and hexadecyltrimethylammonium bromide-Polyethylene glycol hexadecyl ether (C16E20), in the presence of inert salts (NaBr and 3,5-dichlorosodium benzoate), by the use of reaction probe between Pp and ionized PhSH (Pp = piperidine and PhSH = phenyl salicylate), has been reported in this work. The values of RXBr (RXBr denotes ion exchange constants obtained in the presence of micelles of different structural features) or KXBr (KXBr denotes ion exchange constants obtained in the presence of micelles of the same structural features) for 3,5-Cl2C6H3CO2- were almost the same at three different [HDABr]T (0.006, 0.010 and 0.015 M). The average value of RXBr or KXBr determined, in the presence of pure HDABr micelles, using semi empirical kinetic (SEK) method appeared to be almost 2½-fold larger (RXBr or KXBr = 198) than that in the presence of mixed HDABr-C16E20 micelles (RXBr or KXBr = 78). Rheological measurements indicated the existence of wormlike/twisted micelles and vesicle at 0.015 M pure HDABr, various [3,5-Cl2C6H3CO2Na], and 25 and 35℃ whereas there were evidence of only spherical micelles in the presence of mixed HDABr-C16E20 ([HDABr]T = 0.015 M and [C16E20]T = 0.006 M) at both temperatures.

Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases.

Impact of semi-solid formulations on skin penetration of iron oxide nanoparticles.

BACKGROUND: This work aimed to provide useful information on the incidence of the choice of formulation in semi-solid preparations of iron-oxide nanoparticles (IONs). The appropriate analytical methods to assess the IONs physical stability and the effect of the semi-solid preparations on IONs human skin penetration were discussed. The physical stability of IONs (Dh = 31 ± 4 nm; ζ = -65 ± 5 mV) loaded in five semi-solid preparations (0.3% w/v), namely Carbopol gel (CP), hydroxyethyl cellulose gel (HEC), carboxymethylcellulose gel (CMC), cetomacrogol cream (Cet) and cold cream was assessed by combining DLS and low-field pulsed NMR data. The in vitro penetration of IONs was studied using human epidermis or isolated stratum corneum (SC). RESULTS: Reversible and irreversible IONs aggregates were evidenced only in HEC and CMC, respectively. IONs diffused massively through SC preferentially by an intercellular pathway, as assessed by transmission electron microscopy. The semi-solid preparations differently influenced the IONs penetration as compared to the aqueous suspension. Cet cream allowed the highest permeation and the lowest retained amount, while cold cream and CP favored the accumulation into the skin membrane. CONCLUSION: Basic cutaneous semi-solid preparations could be used to administer IONs without affecting their permeation profile if they maintained their physical stability over time. This property is better discriminated by low-field pulsed NMR measurements than the commonly used DLS measurements.

Simplified Enrichment of Plasma Membrane Proteins from Arabidopsis thaliana Seedlings Using Differential Centrifugation and Brij-58 Treatment.

The plasma membrane (PM) forms a barrier between a plant cell and its environment. Proteins at this subcellular location play diverse and complex roles, including perception of extracellular signals to coordinate cellular changes. Analyses of PM proteins, however, are often limited by the relatively low abundance of these proteins in the total cellular protein pool. Techniques traditionally used for enrichment of PM proteins are time consuming, tedious, and require extensive optimization. Here, we provide a simple and reproducible enrichment procedure for PM proteins from Arabidopsis thaliana seedlings starting from total microsomal membranes isolated by differential centrifugation. To enrich for PM proteins, total microsomes are treated with the nonionic detergent Brij-58 to decrease the abundance of contaminating organellar proteins. This protocol combined with the genetic resources available in Arabidopsis provides a powerful tool that will enhance our understanding of proteins at the PM.

The influence of cetomacrogol ointment processing on structure: A definitive screening design.

Batch-to-batch variability is a challenge for the industrial scale production of ointments. Therefore the current investigation focussed on identifying and understanding critical process parameters (CPPs) for cetomacrogol ointment. This was evaluated using a definitive screening design (DSD) approach in which fourteen batches were produced under predefined and controlled conditions using the following variables: addition of SiO2 nanoparticles, mixing speed, cooling rate, heating temperature, container filling temperature and isothermal mixing at the filling temperature. Ointment structure was evaluated using a number of rheological parameters. One of these parameters, yield stress was found to be strongly influenced by filling temperature and mixing speed (p=0.0065 and p=0.0013 respectively). Both significantly affect ointment structure and they also have a significant interaction (p<0.05). Understanding the ointment production process can help in defining a processing window to produce ointment of constant quality.

Nonionic surfactant structure on the drug release, formulation and physical properties of ethylcellulose microspheres.

Evaluate the effects of nonionic surfactants Brij 58 and Tween 40 with different structures but similar hydrophilic lipophilic balances (HLBs) on theophylline (TH)-loaded ethylcellulose (EC) microspheres. Microspheres were formulated using ratios of the surfactants with matching HLB values but different chemical-structures at temperatures (22/35 °C) by hydrophobic solvent-emulsion evaporation. Particle size, GMD, drug loading, encapsulation efficiency and dissolution were evaluated. Drug release was determined using the zero- and first-order, Higuchi and Hixson-Crowell models. EC microspheres prepared with surfactant Brij 58 showed discrete, free-flowing spherical particles, solid interiors and increased particle smoothness as temperature increased; those prepared with Tween 40 appeared porous with coarser surface morphology as temperature increased; both were CHLB (Combined HLB) dependent. Dissolution obeyed the Higuchi model drug release for both microspheres prepared with Tween 40 and Brij 58 except for those prepared with Brij 58 at 35 °C, which presented as zero order. The results were ascribed to the different chemical structure of Brij 58 versus Tween 40 and preparation temperature. Surfactant chemical structure is an unreported processing parameter shown here to be important in microsphere formulation. Brij 58 possesses properties unique to its chemical structure that influence pharmaceutical and molecular biopharmaceutical research.

Scrolls: novel microparticulate systems for enhanced delivery to/across the skin.

We describe the scroll system as a new microparticulate structured delivery system for enhanced delivery to/across the skin. The basic components of the scroll system are non-ionic surface active of the type of alkyl polyglycol ethers and a glycol. The unique structures are preserved with addition of various ingredients such as polymers, vegetable oils, pharmaceuticals, and permeation enhancers but are dismissed when amphiphile is withdrawn. The microparticles have a unique scroll structure with multiple "wrapping." Besides enabling superior permeation of drugs into/across the skin, the drugs delivered by scroll systems were more effective in vitro and in vivo compared to controls. Model drugs presented high entrapment capacity in scroll systems. The systems are stable over time and are safe for skin application. In order to form, they require a small number of ingredients, simple preparation method, and are environment friendly. The scroll systems may be new potential tools in the dermal/transdermal pharmaceutical and cosmetic industry.

Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery.

Nanotechnology offers advantages for new drug delivery design by providing drug targeting while minimizing the side effects. Polyoxyethylene 20 cetyl alcohol (CETETH-20) is a surfactant that may form nanostructured systems, such as liquid crystals, when in contact with water/oil, which are structurally similar to biological membranes and may improve skin interaction. The aim of this study was to develop and characterize CETETH 20-based nanostructured systems by combining CETETH-20 with water and different oily phases, including PEG-12-dimethicone for topical drug administration. The systems were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, texture profile analyses (TPA), in vitro cytotoxicity and histopathological analyses of rabbits' skin. Lamellar, hexagonal and cubic phases were identified and their viscoelastic moduli varied according to each phase. The stiffness of the cubic phase was 3-fold higher and twice more adhesive than the hexagonal phase. The formulations did not affect the normal macrophages cells, neither promoted skin irritation. They were spontaneously obtained by simply mixing the components, which corroborates for an ease scaled-up. These results suggest that systems composed of CETETH 20, PEG-12-dimethicone and water are a promising new approach for designing nanostructured topical drug delivery systems.

Electrochemical method assisted immobilization and orientation of myoglobin into biomimetic brij 56 film and its direct electrochemistry study.

A simple cyclic voltammetric method was applied to assemble and orient a model protein, namely, myoglobin (Mb), into a biocompatible Brij 56 film. Ultraviolet-visible and circular dichroism spectra indicated that Mb in Brij 56 matrix preserved its secondary structure. Fourier transform infrared spectra confirmed the formation of hydrogen bonds between Mb and Brij 56. These hydrogen bonds acted as the electron tunnel to transfer electrons from Mb's active sites to the underlying glassy carbon electrode. Effective direct electron transfer of Mb was realized with the presence of a couple of quasi-reversible and well-defined redox peaks at -310 mV (vs standard calomel electrode) in the studied potential range. The peaks were attributed to the redox couple of heme Fe(II)/Fe(III) of the well-oriented Mb in Brij 56 matrix. The surface coverage and the electron transfer rate (ks) of Mb immobilized into the Brij 56 film was ∼4.9×10(-11) mol cm(-2) and 72.6±3.0 s(-1), respectively. An excellent electrocatalytic response of the immobilized Mb toward nitrite in the absence of electron transfer mediators was observed. These results emphasized that the biomimetic Brij 56 could be used as an attractive material for immobilizing proteins and constructing biosensors.

Partitioning of nitroxides in dispersed systems investigated by ultrafiltration, EPR and NMR spectroscopy.

HYPOTHESIS: The partitioning behavior of paramagnetic nitroxides in dispersed systems can be determined by deconvolution of electron paramagnetic resonance (EPR) spectra giving equivalent results with the validated methods of ultrafiltration techniques (UF) and pulsed-field gradient nuclear magnetic resonance spectroscopy (PFG-NMR). EXPERIMENTS: The partitioning behavior of nitroxides with increasing lipophilicity was investigated in anionic, cationic and nonionic micellar systems and 10 wt% o/w emulsions. Apart from EPR spectra deconvolution, the PFG-NMR was used in micellar solutions as a non-destructive approach, while UF based on separation of very small volume of the aqueous phase. FINDINGS: As a function of their substituent and lipophilicity, the proportions of nitroxides that were solubilized in the micellar or emulsion interface increased with increasing nitroxide lipophilicity for all emulsifier used. Comparing the different approaches, EPR deconvolution and UF revealed comparable nitroxide proportions that were solubilized in the interfaces. Those proportions were higher than found with PFG-NMR. For PFG-NMR self-diffusion experiments the reduced nitroxides were used revealing a high dynamic of hydroxylamines and emulsifiers. Deconvolution of EPR spectra turned out to be the preferred method for measuring the partitioning behavior of paramagnetic molecules as it enables distinguishing between several populations at their individual solubilization sites.

Nanostructures of an amphiphilic zinc phthalocyanine polymer conjugate for photodynamic therapy of psoriasis.

Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population worldwide and it severely affects patient quality of life. In this study, an amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG) chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348 nm and 678 nm. A monomolecular micelle of ZPB formed in water with a mean size of 25 nm and zeta potential of -15 mV. The nanostructures aggregated into cloudy precipitates, which were easily dispersed. The nanostructure showed the shell-core structure with the ZnPc segments as the core and the PEG chains as the shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline, light alone, ZPB alone, and the combination of light and ZPB, the combination of light and ZPB showed the best photodynamic therapy of psoriasis based on the light excitation of the photosensitizer ZPB and the psoriasis was nearly cured according to the histopathological investigation. The ZPB nanostructure is a promising anti-psoriasis nanomedicine based on photodynamic therapy.

Heteroepitaxial formation of aligned mesostructured silica films with large structural periodicities from mixed surfactant systems.

Liquid-crystal phases consisting of cylindrical micelles of amphiphilic block copolymers and silica precursors are epitaxially built up on aligned surface micelles formed by an alkyl-PEO surfactant, Brij56, irrespective of the large difference in the intrinsic structural periodicities resulting in the formation of fully aligned mesostructured silica films with large lattice constants. Brij56 works as an alignment controlling agent on rubbing-treated polyimide through selective adsorption from a precursor solution containing the two surfactants, a block copolymer and Brij56, through strong hydrophobic interactions to form an anisotropic surface micelle structure. Aligned mesostructured silica layers with larger periodicities, which dominantly consist of block copolymers, form on these aligned surface micelles by gradually changing the vertical periodicity keeping the lateral intermicelle distance constant. This can be regarded as a kind of heteroepitaxy because the lattice constant at the surface is different from that of the bulk of the film. On the basis of this new concept, highly aligned mesostructured silica films with structural periodicities as large as 10 nm are successfully formed, which has never been achieved when the block copolymers are used alone as the structure-directing agent. The periodicity of the aligned films can precisely be controlled by an appropriate choice of block copolymers and the mixing ratio of the two surfactants, which increases the opportunity for applications of these films with highly anisotropic mesoscale structure.

Ethosomes in hair dye products as carriers of the major compounds of black tea extracts.

OBJECTIVES: This study describes a novel carrier, the ethosome-based system, which is composed of non-ionic surfactants, ethanol, and water. METHODS: Brij(®) 52 (non-ionic surfactants), soya phosphatidylcholine (PC), cholesterol, and the major compounds (caffeine and gallic acid) of black tea extracts were dissolved in the ethanolic phase. The aqueous phase containing Paragon III was heated to 60 °C and mixed with the previous solution. Finally, 3.4 ml NaOH (6.5 N) was added to adjust the pH level to 4.05. The mixture was centrifuged at 2000 g for two minutes, and the precipitate was taken as the end product. Black tea extracts were applied in ethosome-based formulations, and the efficacy of these formulations in penetrating nude mouse skin and in dyeing white hairs was investigated. RESULTS: Compared with an ethanolic solution and black tea extracts, the non-ionic ethosomal delivery system dramatically enhanced the adsorption of black tea extracts onto hair surfaces in vitro. The non-ionic ethosomal system was much more efficient in delivering and facilitating the adsorption of black tea extracts to the hair surface than hydroalcoholic black tea extracts. CONCLUSIONS: This formulation may have potential for development as a hair dye and protective agent.

Facile synthesis of ultrasmall monodisperse "raisin-bun"-type MoO3/SiO2 nanocomposites with enhanced catalytic properties.

We report the preparation of ultrasmall monodisperse MoO3/SiO2 nanocomposites in reverse microemulsions formed by Brij-58/cyclohexane/water. The nanocomposites are of "raisin-bun"-type with 1.0 ± 0.2 nm MoO3 homogeneously dispersed in 23 ± 2 nm silica spheres. Characterization is carried out based on transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectrometry (EDS), X-ray powder diffraction (XRD), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS), inductively coupled plasma-optical emission spectrometry (ICP-OES), N2 sorption measurement, and NH3 temperature-programmed desorption (NH3-TPD). The as-prepared MoO3/SiO2 nanocomposites are microporous and exhibit enhanced catalytic activities for acetalization of benzaldehyde with ethylene glycol and can be repeatedly used 5 times without obvious deactivation. The catalytic performance improvement is attributed to the unique structure and ultrasmall size of the nanocomposites.

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: in vitro evaluation.

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30-49 nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers.