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Aim: Recently, 'coacervation' has been proposed as a new method to prepare fatty acid solid lipid nanoparticles (SLNs). The aim of this work was to encapsulate methotrexate, a hydrophilic anticancer drug, within SLNs obtained by coacervation, through hydrophobic ion pairing and to evaluate the potential efficacy in in vitro and in vivo breast tumor models of drug-loaded nanoparticles., Materials & Methods: Methotrexate-loaded SLN efficacy was evaluated in vitro towards MCF-7 and Mat B-III cell lines (human and murine breast tumor cell lines). Pharmacokinetics of drug-loaded nanoparticles was evaluated in male Wistar rats and biodistribution in a breast tumor model (Mat B-III) in female Fisher rats., Results: Drug-loaded SLNs showed an increased cytotoxicity towards MCF-7 and Mat B-III cell lines compared with free drug. After intravenous administration, drug plasmatic concentration was increased and a major drug accumulation within neoplastic tissue was shown when the drug was loaded in SLNs, compared with drug solution alone. Encapsulation of the drug within nanoparticles also increased its oral uptake after duodenal administration., Conclusion: SLNs are promising vehicles for the delivery of methotrexate, since an increase of efficacy in vitro and a preferential accumulation in breast cancer in vivo were shown. Original submitted 29 October 2010; Revision submitted 19 March 2011.

Curcumin (CU) loaded solid lipid nanoparticles (SLNs) of fatty acids (FA) were prepared with a coacervation technique based on FA precipitation from their sodium salt micelles in the presence of polymeric non-ionic surfactants. Myristic, palmitic, stearic, and behenic acids, and different polymers with various molecular weights and hydrolysis grades were employed as lipid matrixes and stabilisers, respectively. Generally, spherical-shaped nanoparticles with mean diameters below 500 nm were obtained, and using only middle-high hydrolysis, grade-polymer SLNs with diameters lower than 300 nm were produced. CU encapsulation efficiency was in the range 28-81% and highly influenced by both FA and polymer type. Chitosan hydrochloride was added to FA SLN formulations to produce bioadhesive, positively charged nanoparticles. A CU-chitosan complex formation could be hypothesised by DSC analysis, UV-vis spectra and chitosan surface tension determination. A preliminary study on HCT-116 colon cancer cells was developed to evaluate the influence of CU-loaded FA SLNs on cell viability.

Solid lipid nanoparticles (SLN) of fatty acids (FAs) were prepared with a new, solvent-free technique based on FAs precipitation from their sodium salt micelles in the presence of polymeric non-ionic surfactants: this technique was called 'coacervation'. Myristic, palmitic, stearic, arachidic and behenic acid were employed as lipid matrixes. Spherical shaped nanoparticles with mean diameters ranging from 250 to approximately 500 nm were obtained. Different aqueous acidifying solutions were used to precipitate various FAs from their sodium salt micellar solution. Good encapsulation efficiency of Nile Red, a lipophilic model dye, in stearic acid nanoparticles was obtained. The coacervation method seems to be a potentially suitable technique to prepare close to monodisperse nanoparticles for drug delivery purposes.

A method to produce solid lipid nanoparticles (SLN) from W/O/W multiple emulsions was developed applying the solvent-in-water emulsion-diffusion technique. Insulin was chosen as hydrophilic peptide drug to be dissolved in the acidic inner aqueous phase of multiple emulsions and to be consequently carried in SLN. Several partially water-miscible solvents with low toxicity were screened in order to optimize emulsions and SLN composition, after assessing that insulin did not undergo any chemical modification in the presence of the different solvents and under the production process conditions. SLN of spherical shape and with mean diameters in the 600-1200 nm range were obtained by simple water dilution of the W/O/W emulsion. Best results, in terms of SLN mean diameter and encapsulation efficiencies, were obtained using glyceryl monostearate as lipid matrix, butyl lactate as a solvent, and soy lecithin and Pluronic F68 as surfactants. Encapsulation efficiencies up to 40% of the loaded amount were obtained, owing to the actual multiplicity of the system; the use of multiple emulsion-derived SLN can be considered a useful strategy to encapsulate a hydrophilic drug in a lipid matrix.

Insulin-loaded solid lipid nanoparticles (SLN), obtained by the solvent-in-water emulsion-diffusion technique, were produced using isovaleric acid (IVA) as organic phase, glyceryl mono-stearate (GMS) as lipid, soy lecithin and sodium taurodeoxycholate (TDC) as emulsifiers. IVA, a partially water-miscible solvent with low toxicity, was used to dissolve both insulin and lipids. SLN of spherical shape were obtained by simple water dilution of the O/W emulsion. Analysis of SLN content after processing showed interesting encapsulation efficiency with respect to therapeutic doses; moreover, insulin did not undergo any chemical modification within the nanoparticles and most of it remained stable after incubation of the SLN with trypsin solution. The biological activity of insulin, i.e. the ability to decrease glycemia in rats, was not negatively influenced by the SLN production process, as after subcutaneous administration of insulin extracted from SLN to animals, the blood glucose levels were quite similar to those obtained after administration of a conventional insulin suspension. Consequently, SLN seem to have interesting possibilities as delivery systems for oral administration of insulin.

Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability) hamper peptide-containing formulations. Insulin and leuprolide, chosen asmodel peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide. [ABSTRACT FROM AUTHOR]

A preparation method for nanoparticles based on the emulsification of a butyl lactate or benzyl alcohol solution of a solid lipid in an aqueous solution of different emulsifiers, followed by dilution of the emulsion with water, was used to prepare glyceryl monostearate nanodispersions with narrow size distribution. To increase the lipid load the process was conducted at 47±2 °C and in order to reach submicron size a high-shear homogenizer was used. Particle size of the solid lipid nanoparticles (SLN) was affected by using different emulsifiers and different lipid loads. By using lecithin and taurodeoxycholic acid sodium salt, on increasing the GMS percentage from 2.5 to 10% an increase of the mean diameter from 205 to 695 nm and from 320 to 368 nm was observed for the SLN prepared using benzyl alcohol and butyl lactate, respectively. Transmission electron micrographs of SLN reveal nanospheres with a smooth surface. [Copyright &y& Elsevier]

Nanoparticles of griseofulvin, a model drug with poor solubility and low bioavailability, were prepared from water dilutable microemulsions by the solvent diffusion technique. Solvent-in-water microemulsion formulations containing water, butyl lactate, lecithin, taurodeoxycholate sodium salt (TDC) or dipotassium glycyrrhizinate (KG), 1,2-propanediol or ethanol were used. The formation of macroscopically homogeneous, stable, fluid, optically transparent, isotropic solutions (microemulsions) was investigated by constructing pseudo-ternary phase diagrams. In the presence of TDC or KG, microemulsion systems that remained transparent on water dilution could be obtained. The displacement of butyl lactate, with an excess of water, from the internal phase of the microemulsions containing the drug into the external phase, lead to successful fabrication of drug nanosuspensions. Nanoparticle size was dependent on microemulsion composition: using KG, griseofulvin nanoparticles below 100 nm with low polydispersity and an increased dissolution rate were obtained. [Copyright &y& Elsevier]