Biodegradation

Biod├ęgradation is a very important property of nanoparticles for most therapeutic uses, especially for parenteral administration (injection or implantation). Biodegradation has a profound influence on the drug release rate (see Section 5.3). In addition, with the possible exception of vaccines, the nanoparticle carrier material has to be eliminated rather rapidly to avoid an accumulation in the body.

Most natural polymers such as albumin, gelatin, or starch are biodegraded and eliminated rather rapidly due to enzymatic digestion [123-126, 263]. Poly(butyl cyanoacry-late) is also very rapidly biodegradable. It represents the most rapidly biodegrading artificial polymer. After 24 h already about 80% of the polymer is eliminated from body after intravenous injection of poly(butyl cyanoacry-late) nanoparticles [25]. The degradation and elimination of poly(hexyl cyanoacrylate) is considerably more slow [263265]. Poly(alkyl cyanoacrylate) nanoparticles degrade in the body by enzymatic cleavage of the side chain ester bond, and the rate of this process depends on the ester side chain length [266-268]. The degradation was found to occur by surface erosion, because the particle size decreases immediately after incubation and does not show any lag period [269, 270]. Due to the low molecular weights of the poly(alkyl cyanoacrylates) [57, 94] the resulting water soluble polymer acid is the excreted rather rapidly from the body [6].

Poly(lactide) nanoparticles are rapidly degraded by enzymes, especially lipases [123-126]. Again this appears to be degradation on the surface comparable to the poly(alkyl cyanoacrylate) nanoparticles. Some coating materials, for instance poly(vinyl alcohol), largely prevent this degradation, since this coating material cannot be degraded by enzymes [124-126]. Therefore drug release from poly(lactide) nanoparticles coated with poly(vinyl alcohol) release occurs by diffusion only [125]. The degradation of the poly(lactide) nanoparticles from the surface contrasts the degradation process of the larger poly(lactide) micro-spheres (┬╗1 /m) which degrade by hydrolysis and bulk erosion mainly from the center [271-273]. For this reason the particle size of microspheres changes very little during degradation for a considerable time.

Poly(methyl methacrylate) nanoparticles degrade very slowly over periods of years [274]. As a consequence, they are only useful as model particles or, more importantly, as adjuvants for vaccines, where a long persistence of the antigen and a long immune response are desired [39, 275, 276].

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