Characterization of antimicrobial multilayer film based on ethylcellulose-pectin incorporated with nanoemulsions of trans-cinnamaldehyde essential oil.

In this study, polymer solution casting was utilized to fabricate a multilayer film with ethylcellulose (EC) as the outer layers and trans-cinnamaldehyde-loaded pectin as the inner layer. A significant increase in whiteness and UV-visible light blocking capability and a remarkable decrease in total color difference and yellowness of the films were seen via increasing the thickness of EC outer layers. Scanning electronic microscopy observation showed that the inner and outer layers had a smooth and uniform surfaces with clear boundary. The thicker film has better stretchability and strength, but is less flexible than thinner film. Glass transition temperature did not change remarkably with increasing thickness of EC outer layers, but thermal stability was slightly improved. FTIR-ATR spectra revealed the formation of hydrogen bonds between the two adjacent layers. The multilayer films exhibited excellent antimicrobial efficacy against Gram-positive and Gram-negative foodborne pathogens. The results suggested that this multilayer film has potential applications in active food packaging.

Nanoemulsions Embedded in Alginate Beads as Bioadhesive Nanocomposites for Intestinal Delivery of the Anti-Inflammatory Drug Tofacitinib.

Oral administration of nanoparticles (NPs) is a promising strategy to overcome solubility and stability issues of many active compounds. However, this route faces major obstacles related to the hostile gastrointestinal (GI) environment, which impairs the efficacy of orally administered nanomedicines. Here, we propose nanocomposites as a promising approach to increase the retention time of NPs in the intestinal tract by using bio- and mucoadhesive matrixes able to protect the cargo until it reaches the targeted area. A microfluidic-based approach has been applied for the production of tailored nanoemulsions (NEs) of about 110 nm, used for the encapsulation of small hydrophobic drugs such as the anti-inflammatory JAK-inhibitor tofacitinib. These NEs proved to be efficiently internalized into a mucus-secreting human intestinal monolayer of Caco-2/HT29-MTX cells and to deliver tofacitinib to subepithelial human THP-1 macrophage-like cells, reducing their inflammatory response. NEs were then successfully encapsulated into alginate hydrogel microbeads of around 300 µm, which were characterized by rheological experiments and dried to create a long-term stable system for pharmaceutical applications. Finally, ex vivo experiments on excised segments of rats' intestine proved the bioadhesive ability of NEs embedded in alginate hydrogels compared to free NEs, showing the advantage that this hybrid system can offer for the treatment of intestinal pathologies.

Formulation of Pickering emulsions for the development of surfactant-free sunscreen creams.

OBJECTIVE: Pickering emulsions are increasingly used in the pharmaceutical and cosmetic fields, especially for topical applications, since these systems require solid particles as emulsifiers instead of surfactants which are known to cause skin irritation. The solid inorganic nanoparticles (TiO2 and ZnO) used as UV filters in sunscreen formulations may also stabilize emulsion droplets, so that the utility of surfactants may be questioned. Surfactant-free sunscreen emulsions solely stabilized by such nanoparticles (NPs) have been studied. METHODS: The ability of these NPs to stabilize o/w emulsions containing a 'model' oil phase, the C12 -C15 alkylbenzoate, has been assessed. ZnO and hydrophilic silica-coated TiO2 NPs widely used in sunscreen products were used together with their mixtures. The emulsification efficiency, the control of droplet size and the stability of o/w Pickering emulsions solely stabilized by NPs were investigated. A ZnO/TiO2 NPs mixture characterized by a theoretical SPF of 45 was finally used as unique emulsifiers to develop a surfactant-free sunscreen emulsion. RESULTS: Stable Pickering emulsions containing 10 up to 60 wt% of C12 -C15 alkyl benzoate were formulated with 2 wt% ZnO in the aqueous phase. The droplet size was controlled by the solid NPs content with respect to oil and the emulsification process. Hydrophilic TiO2 NPs did not allow the stabilization of emulsions. The substitution of TiO2 for ZnO up to 60-70 wt% in a 20/80 o/w emulsion was successfully performed. Finally, a ZnO/TiO2 NP mixture was tested as unique emulsifier system for the formulation of a sunscreen cream. Despite a lower viscosity, the obtained Pickering emulsion was stable and exhibited a photoprotective effect similar to the corresponding surfactant-based sunscreen cream with an in vitro SPF of about 45. CONCLUSION: Surfactant-free Pickering emulsions can be stabilized by the UV-filter nanoparticles for the manufacture of sunscreen products.

OBJECTIFS: Les émulsions de Pickering sont de plus en plus utilisées dans les domaines pharmaceutique et cosmétique, notamment pour les applications topiques, car ces systèmes utilisent des particules solides comme émulsifiants au lieu de tensioactifs qui sont connus pour provoquer des irritations cutanées. Les nanoparticules inorganiques solides (TiO2 et ZnO) utilisées comme filtres UV dans les formulations d'écran solaire peuvent également stabiliser les gouttelettes d'émulsion, de sorte que l'utilité des tensioactifs peut être remise en question. Des émulsions de protection solaire sans tensioactifs et uniquement stabilisées par de telles nanoparticules (NP) ont été étudiées. MÉTHODES: La capacité de ces NP à stabiliser les émulsions H/E contenant une phase huileuse «modèle¼, le benzoate d'alkyle C12 -C15 , a été évaluée. Des NP de ZnO et de TiO2 couvert de silice hydrophile, que l'on trouve largement dans les produits de protection solaire, ont été utilisées séparément et en mélange. L'efficacité d'émulsification, le contrôle de la taille des gouttelettes et la stabilité des émulsions de Pickering H/E uniquement stabilisées par les NP ont été étudiés. Un mélange de NP ZnO/TiO2 caractérisé par un SPF théorique de 45 a finalement été utilisé comme émulsifiant unique pour développer une émulsion de protection solaire sans tensioactif. RÉSULTATS: Des émulsions de Pickering stables contenant 10 à 60% en poids de benzoate d'alkyle C12 -C15 ont été formulées avec 2% en poids de ZnO dans la phase aqueuse. La taille des gouttelettes était contrôlée par la teneur en NP solides par rapport à l'huile et le procédé d'émulsification. Les NP de TiO2 hydrophile n'ont pas permis la stabilisation des émulsions. La substitution des NP de TiO2 par du ZnO jusqu'à 60-70% en poids dans une émulsion 20/80 H/E a été réalisée avec succès. Enfin, un mélange de NP ZnO/TiO2 a été testé en tant que système émulsifiant unique pour la formulation d'une crème solaire. Malgré une viscosité plus faible, l'émulsion de Pickering obtenue était stable et présentait un effet photoprotecteur similaire à la crème solaire à base de tensioactif correspondante avec un SPF in vitro d'environ 45. CONCLUSION: Les émulsions Pickering sans tensioactifs peuvent être stabilisées par les nanoparticules de filtre UV pour la formulation de produits de protection solaire.

Protein-Based Nanoparticle Preparation via Nanoprecipitation Method.

Nanoparticles are nowadays largely investigated in the field of drug delivery. Among nanoparticles, protein-based particles are of paramount importance since they are natural, biodegradable, biocompatible, and nontoxic. There are several methods to prepare proteins containing nanoparticles, but only a few studies have been dedicated to the preparation of protein- based nanoparticles. Then, the aim of this work was to report on the preparation of bovine serum albumin (BSA)-based nanoparticles using a well-defined nanoprecipitation process. Special attention has been dedicated to a systematic study in order to understand separately the effect of each operating parameter of the method (such as protein concentration, solvent/non-solvent volume ratio, non-solvent injection rate, ionic strength of the buffer solution, pH, and cross-linking) on the colloidal properties of the obtained nanoparticles. In addition, the mixing processes (batch or drop-wise) were also investigated. Using a well-defined formulation, submicron protein-based nanoparticles have been obtained. All prepared particles have been characterized in terms of size, size distribution, morphology, and electrokinetic properties. In addition, the stability of nanoparticles was investigated using Ultraviolet (UV) scan and electrophoresis, and the optimal conditions for preparing BSA nanoparticles by the nanoprecipitation method were concluded.

Combination of PCR and dual nanoparticles for detection of Plasmodium falciparum.

Highly reactive particle-based DNA amplification was developed for the detection of the Pfg377 gene from P. falciparum gametocytes using functional magnetic latex particles (MLPs) and quantum dots encapsulated polymer particles (QDs-PPs). Firstly, MLPs were prepared from the precipitation of iron oxide, polymerization using initiator, and adsorption of aminodextran (AMD) so as to provide amino-functionalized MLPs. Furthermore, amino-containing polymer particles (PPs) were prepared by emulsifier-free polymerization and encapsulated with fluorescent quantum dots (QDs) for use as a signaling support. Subsequently, poly(maleic anhydride-alt-methyl vinyl ether) (PMAMVE) copolymer was effectively used for rapid and simple grafting of amino-modified DNA primers onto the surface of amino-functionalized particles thereby providing a promising method for particle immobilization. Herein, primer-grafted particles were applied in the amplification of the Pfg377 gene using the PCR approach. After amplification, PCR products containing PMAMVE-grafted MLPs and QDs-PPs were separated using a magnet and examined via a fluorescence microscope. PMAMVE-grafted particles were not found to inhibit the PCR reaction while facilitating efficient fluorescent detection of the PCR product. Results showed high sensitivity and specificity for the detection of amplified Pfg377 gene within only a few steps. This procedure represents a novel improvement to the post-amplification analysis.

Sponge like microparticles for drug delivery and cosmeto-textile use: Formulation and human skin penetration.

This unique work is targeted to achieve three main goals: i) to enhance the aqueous solubility of three specifically selected hydrophobic active agents, ii) to prepare such polymeric biodegradable microparticles which can encapsulate actives-cyclodextrin complexes and iii) to functionalize a polyamide base textile with active loaded microparticles and active-cyclodextrin loaded microparticles. To achieve this objective, biodegradable cationic microparticles were prepared via double emulsion solvent evaporation process and were loaded with hydroxypropyl-beta-cyclodextrin based complexes of Indomethacin, α-tocopheroland Lauryl Isoquinolinium Bromide during the formulation process. Inclusion complex based particles were evaluated for their morphology, size distribution, zeta potential, skin penetration aptitude and adsorption onto a selected textile. It was observed that active-cyclodextrin complex encapsulation do not affect the morphology, size and zeta potential of the microparticles as well as adsorption of the microparticles onto textile remains unaltered. However such active-cyclodextrin complex encapsulated particles provided the enhancement in the aqueous solubility of hydrophobic agents and also provided prolonged release formulations.

Polycaprolactone Based Nanoparticles Loaded with Indomethacin for Anti-Inflammatory Therapy: From Preparation to Ex Vivo Study.

PURPOSE: This work focused on the preparation of polycaprolactone based nanoparticles containing indomethacin to provide topical analgesic and anti-inflammatory effect for symptomatic treatment of inflammatory diseases. Indomethacin loaded nanoparticles are prepared for topical application to decrease indomethacin side effects and administration frequency. Oppositely to already reported works, in this research non-invasive method has been used for the enhancement of indomethacin dermal drug penetration. Ex-vivo skin penetration study was carried out on fresh human skin. METHODS: Nanoprecipitation was used to prepare nanoparticles. Nanoparticles were characterized using numerous techniques; dynamic light scattering, SEM, TEM, DSC and FTIR. Regarding ex-vivo skin penetration of nanoparticles, confocal laser scanning microscopy has been used. RESULTS: The results showed that NPs hydrodynamic size was between 220 to 245 nm and the zeta potential value ranges from -19 to -13 mV at pH 5 and 1 mM NaCl. The encapsulation efficiency was around 70% and the drug loading was about 14 to 17%. SEM and TEM images confirmed that the obtained nanoparticles were spherical with smooth surface. The prepared nanoparticles dispersions were stable for a period of 30 days under three temperatures of 4°C, 25°C and 40°C. In addition, CLSM images proved that obtained NPs can penetrate the skin as well. CONCLUSION: The prepared nanoparticles are submicron in nature, with good colloidal stability and penetrate the stratum corneum layer of the skin. This formulation potentiates IND skin penetration and as a promising strategy would be able to decline the side effects of IND.

Formulation of orodispersible films for paediatric therapy: investigation of feasibility and stability for tetrabenazine as drug model.

OBJECTIVES: Orodispersible films (ODF) were formulated to facilitate tetrabenazine (TBZ) administration to paediatric population for the treatment of hyperkinetic movement disorders. METHODS: ODF were obtained by solvent casting/evaporation method using four different polymers (HPMC, PVP, pullulan and HEC). Physicochemical, mechanical and biopharmaceutical characterizations as well as API state in ODF by thermal analysis were investigated to define and compare formulations. ODF stability was also monitored during 6 months to follow evolution of properties. KEY FINDINGS: Analyses at T0 showed few differences between formulations: results of physicochemical and mechanical characterizations were almost similar for each formulation and TBZ appeared at the amorphous state in all cases. ODF delivery system allowed a major improvement of TBZ dissolution profile in buccal conditions compared with pure drug. However, after 3 and 6 months of stability, a TBZ recrystallization occurred for formulations based on PVP and HEC associated with a decrease of drug release in saliva conditions. CONCLUSIONS: HPMC-ODF (F1) appeared as the best formulation. Indeed, physicochemical, mechanical and biopharmaceutical characteristic remained intact. In addition, TBZ remained in amorphous state during stability study.

Aminodextran polymer-functionalized reactive magnetic emulsions for potential theranostic applications.

Aminodextran (AMD) polymer was prepared via chemical grafting of hexamethylenediamine on oxidized dextran. Magnetic latex particles were successfully obtained by adsorption of positively charged AMD on negatively charged submicron magnetic emulsion. The adsorbed amount was found to be ranged from 20 to 1280mg of AMD per gram of dried magnetic dispersion. The AMD-coated magnetic emulsions were characterized by positive zeta potential in the pH range from 3 to 9 compared to bare seed magnetic emulsion. All the samples showed to be superparamagnetic property, even after the adsorption of the polymer. The developed magnetic submicron particles exhibited good potential for in vivo biomedical diagnosis applications as demonstrated by their higher T2 contrast-ability compared to Gd in magnetic resonance imaging (MRI) and hyperthermia.

Large-scale preparation of clove essential oil and eugenol-loaded liposomes using a membrane contactor and a pilot plant.

Based on our previous study where optimal conditions were defined to encapsulate clove essential oil (CEO) into liposomes at laboratory scale, we scaled-up the preparation of CEO and eugenol (Eug)-loaded liposomes using a membrane contactor (600 mL) and a pilot plant (3 L) based on the principle of ethanol injection method, both equipped with a Shirasu Porous Glass membrane for injection of the organic phase into the aqueous phase. Homogenous, stable, nanometric-sized and multilamellar liposomes with high phospholipid, Eug loading rates and encapsulation efficiency of CEO components were obtained. Saturation of phospholipids and drug concentration in the organic phase may control the liposome stability. Liposomes loaded with other hydrophobic volatile compounds could be prepared at large scale using the ethanol injection method and a membrane for injection.

Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range.

A safe and practical method for the preparation of 7α-thioether and thioester derivatives of spironolactone.

Spironolactone is a renal competitive aldosterone antagonist. One of its most important metabolite is the 7α-methylthio spironolactone: thus it is very important to have an efficient and safe access to this compound, for pharmacokinetic studies. In this context, we synthesized this metabolite by thioalkylation of 7α-thio spironolactone using Hünig's base with a very good yield. We also used our procedure to prepare, with an easy work-up and high yields, 7α-thioether and thioester derivatives of spironolactone, that could be useful for further Structure-Activity Relationships studies.