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kinetically studied. The pro¿ les of release from the microspheres with different di-
ameters 4, 9, 63, and 92 ȝm present the progression of nonlinear and linear stages.
Diffusion kinetic equation describing both linear (PHB hydrolysis) and nonlinear (dif-
fusion) stages of the dipyridamole release pro¿ les from the spherical subjects has been
written down as the sum of two terms: desorption from the homogeneous sphere in
accordance with diffusion mechanism and the zero order release. In contrast to the
diffusivity dependence on microsphere size, the constant characteristics of linearity
are scarcely affected by the diameter of PHB microparticles. The view of the kinetic
pro¿ les as well as the low rate of dipyridamole release are in satisfactory agreement
with kinetics of weight loss measured
in vitro
for the PHB ¿ lms and observed quali-
tatively for PHB microspheres. Taking into account kinetic results, it was supposed
that the degradation of both ¿ lms and PHB microspheres is responsible for the linear
stage of dipyridamole release pro¿ les. Thus, a good method for production of systems
with sustained drug release was demonstrated. The sustained invariable drug release
is an essential property of injectable therapeutic polymer systems that allows to keep
constant the adjusted drug dosing. The PHB ¿ lms and microspheres with sustained
uniform drug release for more that 1 month were developed (Figure 9) [24,127, 129].
FIGURE 9
The PHB microspheres for sustained delivery of drugs (A) PHB microspheres
(average diameter = 63 ȝm, PHB M
w
= 1000 kDa) loaded with dipyridamole (10% w/w), (B)
sustained delivery of dipyridamole from PHB microspheres for more than 1 month [24, 131].
The biocompatibility and pharmacological activity of advanced drug delivery sys-
tems on the base of PHB was studied [24, 58, 117, 128]. It was shown that implanted
PHB ¿ lms loaded with dipyridamole and indomethacin caused the mild tissue reac-
tion. The inÀ ammation accompanying implantation of PHB matrices is temporary and
additionally toxicity relative to normal tissues is minimal [24]. No signs of toxicity
were observed after administration of PHB microspheres loaded with analgesic, tra-
madol, [128]. A single intraperitoneal injection of PHB (M
w
= 450 kDa) microspheres
containing anticancer prodrugs, butyryl-FUDR and pentanoyl-FUDR, resulted in high
antitumor effects against P388 leukemia in mice over a period of ¿ ve days [58]. Em-
bolization with PHB microspheres
in vivo
on dogs as test animals has been studied
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