Nanocrystals: Production, Cellular Drug Delivery, Current and Future Products - Intracellular Delivery: Fundamentals and Applications - page 420

Fig. 3 The nanoparticles are differentiated in class I-IV with increasing toxicological risk,
based on size (<100 nm, 100-1,000 nm) and biodegradability/non-biodegradability (i.e. persis-
tency in the body) (Modified after Müller, Gohla, and Keck, submitted )
endocytosis/pinocytosis, having therefore a higher potential risk. Nanoparticles
which are biodegradable in the body will disappear after some time, thus potential
undesired effects are often limited to the time of existence of the particles.
Biodegradable nanoparticles are therefore also a lower risk class. Non-biodegradable
particles such as e.g. fullerens and carbon nanotubes (CNT) - often discussed as
potential drug delivery systems - will stay forever. Non-biodegradable particles can
cause continuing irritations, thus being excluded for the use as drug delivery sys-
tem. Based on these considerations, the nanocrystals are in the lowest risk class I,
or in class III depending on the size above or below 100 nm.
It should be kept in mind that also a biodegradable nanoparticle can cause toxic
effects. For example during their life time biodegradable nanoparticles can be taken
up by cells of the immune system and can cause irritation/activation of the immune
system. Therefore also in this case assessment of potential nanotoxicity risks is
meaningful. Assumingly because of the a priori assumed lack of nanotoxicty of
the nanocrystals, there are very few reports about cytotoxicity investigations. Oral
nanocrystal products are on the pharmaceutical market since 10 years, but no
systematic investigations are published. Good tolerability can be assumed because
mankind lives for centuries with drug nanocrystals present in the gastrointestinal
tract (GIT). Each drug crystal orally administered will reduce in size during its
dissolution, to a few mm and finally to the nanometer range prior to its complete
dissolution. Nanosuspensions were mainly investigated regarding treatment effi-
ciency, in vitro and in vivo, less looking at toxic effects. For example, the efficacy
of atovaquone nanosuspensions was investigated against toxoplasma gondii in vitro