Nanobusiness Butterfly

Dr. Samuli Hirsjärvi – Nanoparticles for pharmaceutical use

25.03.2010 14:20

Thesis

Link to the dissertation: http://urn.fi/URN:ISBN:978-952-10-4456-4

Classification

Nano in human well-being

Abstract

Nanoparticles have versatile potential for efficient exploitation of different drug delivery formulations and routes because of the properties provided by their small size. These possible benefits include controlled release, protection of the active pharmaceutical ingredient and drug targeting. Nanoparticles are expected to offer new solutions e.g. for gene therapy and delivery of peptide drugs. Generally, nanoparticles are applied as an injectable or oral solution, but their use as dried material in formulations such as tablets or inhalable powders is equally conceivable. Although the research on pharmaceutical nanoparticles has been extensive during recent years, breakthrough of products to the market has not yet occurred. Problems like poor drug encapsulation efficiency and difficulties in controlling and scaling up of the preparation process have inhibited progress.

In this study, nanoparticles were prepared from a biodegradable poly(lactic acid) (PLA) polymer. Knowledge and understanding of properties of the materials used in the particle preparation as well as behavior of the nanoparticles in different environments are essential in order to create successful nanoparticle formulations and to predict their performance in the body. Therefore, the effect nanoprecipitation, a nanoparticle preparation method, on the physicochemical properties of the polymer and model drugs encapsulated in the nanoparticles as well as the effect of the drugs on the polymer were studied by thermoanalytical and spectroscopic methods. The suitability of capillary electrophoresis for drug quantitation in the nanoparticle formulations was estimated. Surface pressure measurements were applied for the assessment of stability and aggregation of the nanoparticles. The protective ability of carbohydrates to improve the freeze-drying process of the nanoparticles was evaluated. Finally, a layer-by-layer polyelectrolyte coating process, which modifies the particle surface properties, was introduced. Analytical methods such as electron microscopy, size measurements and zeta potential determinations were included in the nanoparticle characterization.

Both the preparation process as well as the drugs affected the physicochemical characteristics of the nanoparticles such as particle size and crystallinity of the polymer, and, further, the stability of the PLA nanoparticles. With a combination of surface pressure measurements and electron microscopy observations, it was possible to gain information about conditions and progression of nanoparticle aggregation and the role of the stabilization mechanisms. Stability of nanoparticle dispersion was a prerequisite for completion of the layer-by-layer coating. Utilization of protective excipients, glucose and lactose in this study, was found to be indispensable for the freeze-drying. Capillary electrophoresis appeared to be a promising tool for the quantitation of drug encapsulation and subsequent drug release. The results of this study provide information about the materials used and the methods applied for further studies that aim at development of biocompatible and biodegradable nanoparticles for human use.

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