Double crosslinked interpenetrated network in nanoparticle form for drug targeting--preparation, characterization and biodistribution studies.

The development of polymer nanosystems able to target and control/sustain the drug delivery is still considered an important desideratum in pharmaceutical research. The present study reports the preparation of nanoparticles based on chitosan and gelatin, using a reverse emulsion-double crosslinking (ionic followed by covalent one) technique. The nanoparticles structural and morphological characteristics (diameter and size distribution), their swelling capacity in aqueous media of different pH (4 and 7.4) and their ability to include and release poorly water-soluble drugs were seen to be influenced by the composition of the polymer mixture and by the surfactants concentration. Also, nanoparticles biodistribution after intraperitoneal or intravenous administration was evaluated by polymer marking with fluorescein. Particles ability to penetrate different organs (liver, heart, lungs, and less brain, gums, testicles) was increased when injected intravenously.

Covalent and ionic co-cross-linking--an original way to prepare chitosan-gelatin hydrogels for biomedical applications.

The first goal of this work was to develop a method for obtaining interpenetrating gelatin (G)-chitosan (CS) networks prepared by double cross-linking (covalent followed by ionic) that exhibit hydrogel character. The second goal was to modulate their properties as a function of the preparation parameters by using neural network models. This study was therefore carried out by experiment and simulation. The covalent cross-linking resulted from the reaction between the carbonyl groups of glutaraldehyde with amino groups belonging to both polymers; the ionic cross-linking is based on the interaction between tripolyphosphate anions and protonated amine groups (ammonium ions) of the polymers. The total cross-linking density (indirectly assessed by estimating the water swelling capacity) and the ability to include hydrosoluble bioactive principles are influenced by the following process parameters: the CS/G ratio, the amount of ionic cross-linker, and the ionic cross-linking time. The prepared hydrogels were characterized with respect to their structural, morphological, and some physical properties. The hydrogels ability to load high amounts of water-soluble drugs indicates their potential use as carriers for biologically active principles in the human body. A neural network methodology was applied to model the swelling degree and caffeine loading/release capacity depending on reaction conditions; in addition, applying this method, the optimal preparation conditions have been determined, targeting pre-established values for swelling degree or maximum caffeine value. The accuracy of the results obtained through this technique proves that the neural networks are suitable tools for modeling cross-linking processes taking place complex nonlinear polymers.