Biomedical Engineering Reference
In-Depth Information
Polylactic acid (PLA) and PLGA have been used for more than three decades for a variety of
medical applications. Extensive research has been devoted to the use of these polymers as carriers
for controlled drug delivery of a wide variety of bioactive agents. Mathiowitz and group intro-
duced the concept of bioadhesive oral delivery system based on bioerodible polyanhydrides [57].
Bioerodible materials, which provide a continuously renewable cluster of carboxyl groups, might
demonstrate a long duration of bioadhesiveness even though they do not possess fl exible poly-
mer chains as found in the case of hydrogels. Poly(fumaric-
co
-sebacic) [P(FA:SA)] was reported
as the most bioadhesive polymer system from a series of thermoplastic materials evaluated [58].
Polyanhydride microspheres displayed strong interactions with mucus lining and cellular lining.
P(FA:SA) microspheres transverse both mucosal absorptive epithelium and FAE covering the lym-
phoid tissues of Peyer's patches. This material was proposed as novel oral delivery system for insulin
and other peptide drugs. P(FA:SA) microspheres increase the absorption of three model substances
of widely varying molecular size: dicumarol, insulin, and plasmid DNA.
Poly(a l k yl cya noacr ylate) na nocapsules were successf ully used for oral l ad m in ist ration of insul in
in diabetic rats [59]. Insulin-loaded nanospheres (100 IU/kg of body weight) that were administered
perorally in streptozotocin-induced diabetic rats provoked a 50% decrease of fasted-glycemia from
the second hour up to 10-13 days. When
14
C-labeled nanospheres loaded with
125
I insulin were
used, it was found that nanospheres increased the uptake of insulin or its metabolites in the GIT,
blood, and liver, while the excretion was delayed when compared with
125
I insulin nonassociated to
nanospheres; in addition,
14
C and
125
I radioactivities disappeared progressively as a function of time,
parallel to the biological effect.
Poly(isobutyl cyanoacrylate) (PIBCA) nanocapsules were dispersed in a biocompatible micro-
emulsion to facilitate the absorption of insulin following intragastric administration to diabetic rats
[60]. Insulin-loaded PIBCA nanocapsules were prepared
in situ
in a biocompatible water-in-oil
microemulsion by interfacial polymerization. Subcutaneous administration of insulin-loaded nano-
capsules to diabetic rats demonstrated that the bioactivity of insulin was retained, and intragastric
administration of insulin-loaded nanocapsules resulted in a signifi cantly greater reduction in blood
glucose levels of diabetic rats.
In vivo
performance of insulin-loaded PIBCA nanospheres with or
without sodium cholate and Pluronic F68 surfactants were studied on alloxan-induced diabetic rats
[61]. Administered orally, insulin-loaded (75 IU/kg) nanospheres, in the presence of surfactants,
signifi cantly reduced the mean blood glucose level for more than 8 h. These fi ndings suggest the
possible application of surfactant-incorporated polymeric nanoparticles for improving gastrointes-
tinal absorption of insulin.
Nanoparticles prepared with a blend of a biodegradable polyester poly(
ε
-caprolactone) and a
polycationic nonbiodegradable acrylic polymer (Eudragit (R) RS) were used for oral administra-
tion of insulin [62]. When administered orally by force-feeding to diabetic rats, insulin nanopar-
ticles decreased fasted-glycemia in a dose-dependant manner with a maximal effect observed
with 100 IU/kg. These insulin nanoparticles also increased serum insulin levels and improved
the glycemic response to an oral glucose challenge for a prolonged period of time. Insulin-loaded
poly(lactic-
co
-glycolic acid) nanoparticles were prepared by a double-emulsion solvent evapora-
tion method [63]. After oral administration of 10 IU/kg nanoparticles, the plasma glucose level
decreased signifi cantly after 4 h (
p
<
0.05); 10 h later, the glucose level decreased to the lowest
(52.4
0.8%.
Biodegradable nanoparticles loaded with insulin-phospholipid complex were prepared by a novel
reverse micelle-solvent evaporation method in which soybean phosphatidylcholine (SPC) was
employed to improve the liposolubility of insulin and biodegradable polymers as carrier materi-
als to control drug release [64]. Intragastric administration of the 20 IU/kg nanoparticles reduced
fasting plasma glucose levels to 57.4% within the fi rst 8 h of administration, and this reduction
was continued for 12 h. Pharmacokinetic/pharmacodynamics (PK/PD) analysis indicated that
7.7% of oral bioavailability was relative to subcutaneous injection.
±
10.2%,
p
<
0.01), and the relative pharmacological bioavailability was 10.3
±
