Drug release from nanoparticles generally is rather rapid, although also a very slow release has been observed [259, 260]. Again this topic was subject of number of reviews [6, 7, 250, 251, 258].
Release may occur by desorption of surface-bound drug, diffusion through the nanoparticle matrix or nanocapsule wall, matrix erosion, or a combined erosion-diffusion process [6, 7]. After injection into the bloodstream nanoparticles are rapidly opsonized by blood components [198, 261, 262] (see Section 6.1). This adsorptive blood component layer may strongly impede drug release.
In vitro drug release may be studied by a variety of methods . Due to the small size of the nanoparticles the separation of the releasing particles from the rest of the sample represents a major problem. In principle this separation can be achieved in two ways, either by ultracentrifugation or by separation by a membrane, using for instance side-by-side diffusion cells with artificial or biological membranes, dialysis bags, ultrafiltration, and centrifugal ultrafiltration. All these techniques have the common disadvantage that a significant time lapse exists between immediate release from the particle and the time of sampling, because ultrafiltration, membrane diffusion, and ultracentrifugation are all time consuming processes. During this time lapse the release continues; therefore, it is not possible to obtain real time release rates. A very good alternative to study the release is the employment of substances that change their analytic profile, for instance color, by going from a hydrophobic into a hydrophilic environment when traversing from the particle surface into the release medium. Such a compound is the fluorescent marker Prodan®. This marker exhibits a hypsochromic shift from 424 nm in poly(lactate) to 512 nm in water . Unfortunately, this method is compound specific and therefore can only be employed for model experiments.
Moreover, it has to be considered that in very many cases the in vitro release cannot be correlated with the in vivo situation .
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