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The scale-up of nanoemulsions (NEs) produced by emulsification and solvent diffusion process was successfully achieved in the present work. Up to 1500 mL of NEs were produced with olive oil, castor oil, almond oil, or Arlamol™ E by using a Y-shaped mixer device. NE droplet sizes were significantly modulated from 290 to 185 nm by changing the process parameters without modification of the formulation composition. Smaller NE droplet sizes were obtained by (1) decreasing the internal diameter of the Y-mixer from 5 to 0.8 mm, (2) increasing the flow rates of the organic and the aqueous phases upon mixing, and (3) increasing the temperature of the experiment from 5°C to 40°C. All the results of NE diameters (d(sc) ) expressed as a function of the Reynolds number (Re) and the shear rate inside the Y-mixer (\documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$\dot \gamma$\end{document}) showed the existence of typical power-law relationships: d(sc) = 10(2.82) Re(- 0.14) and \documentclass{article}\usepackage{amssymb}\begin{document}\pagestyle{empty}$d_{{\rm sc}} = 10^{2.60} \dot \gamma ^{- 0.06}$\end{document}, respectively. The existence of these power-laws for NE formation by emulsification and solvent diffusion process has never been reported in the literature yet and constitutes a new finding in this work. We definitely proved that the high turbulences created upon NE formation are the most important parameter allowing to decrease droplet size., (Copyright © 2012 Wiley-Liss, Inc.)

This review summarizes the different methods of preparation of polymer nanoparticles including nanospheres and nanocapsules. The first part summarizes the basic principle of each method of nanoparticle preparation. It presents the most recent innovations and progresses obtained over the last decade and which were not included in previous reviews on the subject. Strategies for the obtaining of nanoparticles with controlled in vivo fate are described in the second part of the review. A paragraph summarizing scaling up of nanoparticle production and presenting corresponding pilot set-up is considered in the third part of the review. Treatments of nanoparticles, applied after the synthesis, are described in the next part including purification, sterilization, lyophilization and concentration. Finally, methods to obtain labelled nanoparticles for in vitro and in vivo investigations are described in the last part of this review.

Chitosan-thiobutylamidine was developed and evaluated as a novel tool for gene delivery. The conjugate, displaying 299.1+/-11.5 micromol free thiol groups per gram polymer, formed coacervates with pDNA at a mean size of 125 nm and a zeta potential of +9 mV. Thiol groups, being susceptible for oxidation, were immobilised on the polymeric backbone of chitosan in order to introduce the property of extracellular stability and intracellular pDNA release by forming reversible disulfide bonds. The integrity of the new particles was compared to unmodified chitosan under simulated physiological conditions. Within 10h, pDNA was completely released from chitosan-DNA particles while only 12% were released from the thiomer-based particles. At pH 7, the amount of thiol groups significantly (p<0.05) decreased by more than 25% within 6h. In contrast, in a reducing environment as found intracellularly, chitosan-thiobutylamidine-DNA nanoparticles dissociated continuously, liberating approximately 50% of pDNA within 3h. Transfection studies performed in a Caco2 cell culture evinced the highest efficiency for chitosan-thiobutylamidine-DNA nanoparticles in combination with a glycerol shock solution. The combination of improved stability, enhanced pDNA release under reducing conditions, and higher transfection efficiency identifies chitosan-thiobutylamidine as a promising new vector for gene delivery.

The purpose of this expert review is to discuss the impact of nanotechnology in the treatment of the major health threats including cancer, infections, metabolic diseases, autoimmune diseases, and inflammations. Indeed, during the past 30 years, the explosive growth of nanotechnology has burst into challenging innovations in pharmacology, the main input being the ability to perform temporal and spatial site-specific delivery. This has led to some marketed compounds through the last decade. Although the introduction of nanotechnology obviously permitted to step over numerous milestones toward the development of the "magic bullet" proposed a century ago by the immunologist Paul Ehrlich, there are, however, unresolved delivery problems to be still addressed. These scientific and technological locks are discussed along this review together with an analysis of the current situation concerning the industrial development.

Poly(isobutylcyanoacrylate) nanocapsules with an oily core were originally proposed for lipophilic drug encapsulation [Int. J. Pharm. 28 (1986) 125] but insulin, a hydrosoluble protein, has also been successfully encapsulated by Damgé et al. [Diabetes 37 (1988) 246]. The aim of this work was to understand if several parameters were restrictive for the encapsulation of insulin into the oily core of the nanocapsules prepared by interfacial polymerization. The encapsulation efficiency of insulin was not affected by the type of insulin since the peptides adopted the same association state after their addition to the organic phase. Formulation parameters mainly affected the size of the nanocapsules obtained but did not influence the insulin encapsulation efficiency. In contrast, the order of introduction of insulin and of the monomer in the organic phase was shown to control the formation and the characteristics of the nanocapsules. The key parameters, which were found to clearly influence the encapsulation efficiency of insulin, were the pH of the aqueous insulin solution and the origin of the monomer. Both of these parameters can affect the rate of the interfacial polymerization. Consequently, the ability of insulin to be entrapped into the oil containing nanocapsules appeared to be governed more by the rate of the monomer polymerization.

Purpose: The aim of this work was to synthesize new surface-modified nanoparticles using a radical emulsion polymerization of an alkyl cyanoacrylate., Methods: Isobutyl cyanoacrylate was polymerized in nitric acid 0.2 M containing a polysaccharide (0.1375 g) and cerium (8 x 10(-2) M). After 1 h, the pH was adjusted to 7.0, and the nanoparticles were purified by dialysis. Nanoparticle characterization included scanning electron microscopy, quasi-elastic light scattering, zeta potential determination, measurements of the complement activation induced by different polysaccharide-coated nanoparticles and of the antithrombic activity of heparin., Results: Dispersions of spherical particles were obtained using various polysaccharides. The particle diameter varied from 90 nm to several micrometers, and the zeta potential depended on the molecular weight and the nature and charge of the polysaccharide. Surface analysis performed by ESCA confirmed the presence of polysaccharides at the nanoparticle surface. The nanoparticles were very stable, and the biologic activity of the polysaccharide was preserved. Complement activation was influenced by the polysaccharide characteristics., Conclusions: A new method based on radical emulsion polymerization of isobutyl cyanoacrylate initiated by polysaccharides and cerium was developed to prepare nanoparticles. It leads, in a single step, to nanoparticles with surface properties defined by the polysaccharide. This method is a new concept for the development of biomimetic drug carriers with multiple functions.

Purpose: Biodegradable poly(isobutylcyanoacrylate) nanocapsules have been recognized as a promising carrier for oral administration of peptides and proteins. In the present study, we investigate the fate of insulin-loaded nanocapsules by fluorescence and transmission electron microscopy (TEM) after intragastric force-feeding to rats., Methods: Insulin-, Texas-red-labeled insulin, or gold-labeled insulin-loaded nanocapsules were first characterized. Rats received a single dose of nanocapsules (diameter 60-300 nm, 57 IU insulin/kg) by intragastric force-feeding. After 90 min, ileum was isolated and prepared for fluorescence and transmission electron microscopy., Results: Nanocapsules were observed on both sides of the gut epithelium and in blood capillaries. In M-cell-free epithelium, apparently intact nanocapsules could be seen in the underlying tissue, suggesting they could cross the epithelium and carry the encapsulated peptide. In M-cell-containing epithelium, nanocapsules appeared degraded in the vicinity of macrophages. It is noteworthy that intestinal absorption of nanocapsules was observed without artifacts forcing the nanocapsules to stay in the gut., Conclusions: Based on TEM observations, this study shows the intestinal absorption of biodegradable nanocapsules leading to the transport of insulin across the epithelium mucosa. The fate of the nanocapsules appeared different depending on the presence or the absence of M cells in the intestinal epithelium.

Nanocapsules are submicroscopic colloidal drug carrier systems composed of an oily or an aqueous core surrounded by a thin polymer membrane. Two technologies can be used to obtain such nanocapsules: the interfacial polymerization of a monomer or the interfacial nanodeposition of a preformed polymer. This article is an extended review of these nanocapsule technologies and their applications for the treatment of various diseases (including cancer and infections).

The nanotechnology revolution offers many expectations for the improvement of medicine treatments. At present, nanomedicine (NM) development is hampered by methodological barriers for a better characterization and a wider understanding of their in vivo behavior. While regulatory agencies setup guidelines to support NM translation from bench to bedside, the gap is still hardly overcome by main nanomedicines. One lever for filling this gap is a better characterization, thus increasing the global knowledge about the NM itself but also validate the confidence in terms of batch to batch reproducibility of such complex nano-objects. Here, we review the current methodologies routinely used for clinical release of nanomedicine batches in compliance with official guidelines. We confront them to the extreme sharpness of biological systems and finally discuss future possible orientations for a better characterization of NMs, needed to bridge the gap between physicochemical properties and biological fate. [ABSTRACT FROM AUTHOR]