Development of O/W nanoemulsions for ophthalmic administration of timolol.

After an initial screening of ingredients and production methods, nanoemulsions for ocular administration of timolol containing the drug as maleate (TM) or as ion-pair with AOT (TM/AOT) were prepared. The physico-chemical characterization of nanoemulsions, regarding mean diameter, pH, zeta potential, osmolarity, viscosity and surface tension, underlined their feasibility to be instilled into the eyes. Single components and emulsions were tested ex vivo on rabbit corneas to evaluate corneal irritation, that was measured according to opacity test. A marked decrease in corneal opacity was observed using the drug formulated in nanoemulsions rather than in aqueous solutions. Drug permeation and accumulation studies were performed on excised rabbit corneas. An increase in drug permeation through and accumulation into the corneas were observed using TM-AOT compared to TM due to an increase of lipophilicity of the drug as ion-pair. The introduction of chitosan (a positive charged mucoadhesive polymer) into emulsions allowed to increase TM permeation probably due to the interaction of chitosan with corneal epithelial cells.

Poly(amidoamine)-Cholesterol Conjugate Nanoparticles Obtained by Electrospraying as Novel Tamoxifen Delivery System.

A new poly(amidoamine)-cholesterol (PAA-cholesterol) conjugate was synthesized, characterized and used to produce nanoparticles by the electrospraying technique. The electrospraying is a method of liquid atomization that consists in the dispersion of a solution into small charged droplets by an electric field. Tuning the electrospraying process parameters spherical PAA-chol nanoparticles formed. The PAA-cholesterol nanoparticles showed sizes lower than 500 nm and spherical shape. The drug incorporation capacity was investigated using tamoxifen, a lipophilic anticancer drug, as model drug. The incorporation of the tamoxifen did not affect the shape and sizes of nanoparticles showing a drug loading of 40%. Tamoxifen-loaded nanoparticles exhibited a higher dose-dependent cytotoxicity than free tamoxifen, while blank nanoparticles did not show any cytotoxic effect at the same concentrations. The electrospray technique might be proposed to produce tamoxifen-loaded PAA-chol nanoparticle in powder form without any excipient in a single step.

Electrospray technique for solid lipid-based particle production.

BACKGROUND: Different preparation methods for the production of lipid micro- and nanoparticles as controlled release formulations have been widely developed. Novel techniques are attracting increasing attention for their preparation. METHOD: The objective of the present investigation was to produce solid lipid-based micro-nanospheres using the electrohydrodynamic atomization (electrospraying) and to evaluate whether it is a suitable method to prepare drug-loaded particles. RESULTS: Narrowly dispersed spherical particles lower than 1 mum, easily internalized in cells, were obtained using stearic acid and ethylcellulose in a 4.5:0.5 (w/w) ratio. Tamoxifen, as model drug, was encapsulated with good entrapment efficiency. The in vitro release, after an initial burst effect, showed a prolonged drug release. CONCLUSION: The electrospraying method might be proposed to prepare in a single-step monodisperse lipid-based micro- and nanoparticles in powder form for drug delivery.