The morphology of gelatin nanoparticles loaded with three different drugs (Tizanidine hydrochloride, Gatifloxacin and Fluconazole) and their characteristics of entrapment and release from gelatin nanoparticles were investigated by the analysis on nanoparticle size distribution, SEM and FT-IR in this study. The particles were prepared by nanoprecipitation using water and ethanol as a solvent and a nonsolvent, respectively. The exclusion of a crosslinking agent from the procedure led the system to have an irregularly-shaped morphology. Nonetheless, the uncrosslinked case of Gatifloxacin loading generally led to a more homogeneous population of nanoparticles than the uncrosslinked case of Tizanidine hydrochloride loading. No loading was achieved in the case of Fluconazole, whereas both Tizanidine hydrochloride and Gatifloxacin are observed of being capable of being loaded by nanoprecipitation. Tizanidine hydrochloride-loaded, blank and Gatifloxacin-loaded nanoparticles yielded, under crosslinked condition, 59.3, 23.1 and 10.6% of the used dried mass. The crosslinked Tizanidine hydrochloride-loaded particles showed the loading efficiency of 13.8%, which was decreased to 1.1% without crosslinking. A crosslinker such as glutaraldehyde is indispensable to enhance the Tizanidine hydrochloride-loading efficiency. To the contrary, the Gatifloxacin-loading efficiency for crosslinked ones was lower by a factor of 2-3 times than that for uncrosslinked ones. This is due to the carboxylic groups of Gatifloxacin and the aldehyde groups of glutaraldehyde competing with each other during the crosslinking process, to react with the amino groups of gelatin molecules. The loading efficiency of gelatin nanoparticles reported by other investigators greatly varies. Nevertheless, the loading efficiency reported by us is in good agreement with the drug-loading data of gelatin nanoparticles reported by other investigators. The 80% of loaded Tizanidine hydrochloride was released around 15 h after start-up of the release experiment, while the 20% of loaded Gatifloxacin was released more rapidly, as free Gatifloxacin, than the loaded Tizanidine hydrochloride and it showed the trend of sustained slow release during the remaining period of its release experiment. Furthermore, the result of comparative FT-IR analysis is consistent to that of the corresponding drug release study.

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This study focuses on the novel preparation of gelatin nanoparticles by nanoprecipitation. The principal parameters studied for its optimum conditions were the concentration of emulsifier, the time of emulsifier addition, the concentration of gelatin in solvent phase and the non-solvent volume. In addition, the effect of type of non-solvent (ethanol, n-propanol, methanol) was also studied. It was notable that emulsifier should exist in the non-solvent phase to prevent aggregation of gelatin nanoparticles prepared by nanoprecipitation. The emulsifier to gelatin mass ratio of 32:1 was found to be appropriate to fabricate stable nanoparticles without inter-particle aggregation caused by charge neutralization, during the course of cross-linking. The yield of gelatin nanoparticles was calculated gravimetrically after freeze drying. The freeze-dried nanoparticles were characterized for size and morphology by scanning electron microscopy. The division between nanoparticles was found most clear and vivid in the freeze-drying-induced matrix, owing to the least inter-particle aggregation during the process of cross-linking, for the case of 2% (w/v) emulsifier. The morphology of the freeze-dried nanoparticles turned out to be a spherical or hexagonal regular shape with a smooth surface in the freeze-drying-induced matrix. Their number-mean size is barely 115 nm and their unimodal size-mean is 215 nm with an unimodal polydispersity of 0.1547, the former of which is much smaller and the latter belongs to the lower limit of the gelatin nanoparticle size of 200-500 nm prepared by the coacervation method. Thus, as far as the morphology and the size of prepared gelatin nanoparticles are concerned, the optimum conditions may be derived from those of the above-mentioned morphology. The comparative experiments performed using the coacervation method turned out to require stirring and the nanoparticles still exhibited stability problems, even in the presence of emulsifier. Therefore, the results presented in this study show the optimum conditions and reflect the unexploited potential of the nanoprecipitation method for the preparation of nanoparticles from hydrophilic polymers like gelatin.

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