content in a slow controlled way, preferably in linear fashion. In a model study,
chitosan beads loaded with BSA were obtained by dropping a chitosan albumin
mixture in a alginate coagulation bath [48]. Beads were obtained that were amenable
to controlled release depending on the fluid in which the beads were incubated. After
a successful study with BSA as model compound, these chitosan-alginate beads
loaded with ampicillin showed nearly complete drug retention in mimicked gastric
conditions in simulated gastric fluid (SGF) but released their content in simulated
intestinal fluid (SIF). Bead formation was studied in the presence of competitive
cations Ca
2+ and Ba
2+ in order to change the release characteristics of the beads [48].
Addition of barium to the system revealed the conditions at which a linear release
over about 24 h could be accomplished.
A capsule of chitosan with an enteric coating and filled with the marker carboxy
fluoresceine and a low molecular weight enhancer has been studied for uptake in the
colon. In preliminary studies, dodecyl maltose was show to be a more effective
enhancer than sodium glycocholate, sodium salicylate and sodium caprate. All four
enhancers were more active in the colon but the maltose compound was the best.
This was tested in the capsule. The capsule containing the maltose compound and
the fluoresceine marker was applied orally and gave rise to the highest plasma
fluorescence. A solution or gelatin capsules were less effective. The capsule is a
candidate for controlled, colon-specific uptake. It should be noted that colonspecific delivery can also be accomplished by coating a capsule with pectin. This
is only dissolved in the large intestine. There are interesting possibilities in combination with chitosan.
The N-acetyl chitosans are the most interesting for controlled release.
Galactosylated chitosan microspheres have been prepared. Production of more
specific oligoglycoside-chain chitosan might develop into active targeting of specific tissues. Pectinate gel beads modified with trimethyl chitosan have been
prepared and evaluated for colon targeted delivery of macromolecules.
Chitosan beads containing prednisolone were implanted in mouse skin within
induced local inflammatory air pouches. These chitosan beads are biocompatible
and biodegradable vehicles for treatment. An effective dose can be given in
combination with prolonged periods of local drug presence. This compares advantageously with injection of a prednisolone suspension.
6.3 Chitosan Nanoparticles for Drug Delivery, Gene Therapy
and Cancer Therapy
Among the various drug delivery systems, nanoparticles have several advantages,
such as high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release, cell
internalization as well as the ability to reverse the multidrug resistance of tumour
cells. They could also provide one solution for delivery of new classes of active
molecules such as peptides, proteins, genes and oligonucleotides. However, the
Biopolymeric Micro- and Nanoparticles: Preparation, Characterization and. . .
289
chitosan beads loaded with BSA were obtained by dropping a chitosan albumin
mixture in a alginate coagulation bath [48]. Beads were obtained that were amenable
to controlled release depending on the fluid in which the beads were incubated. After
a successful study with BSA as model compound, these chitosan-alginate beads
loaded with ampicillin showed nearly complete drug retention in mimicked gastric
conditions in simulated gastric fluid (SGF) but released their content in simulated
intestinal fluid (SIF). Bead formation was studied in the presence of competitive
cations Ca
2+ and Ba
2+ in order to change the release characteristics of the beads [48].
Addition of barium to the system revealed the conditions at which a linear release
over about 24 h could be accomplished.
A capsule of chitosan with an enteric coating and filled with the marker carboxy
fluoresceine and a low molecular weight enhancer has been studied for uptake in the
colon. In preliminary studies, dodecyl maltose was show to be a more effective
enhancer than sodium glycocholate, sodium salicylate and sodium caprate. All four
enhancers were more active in the colon but the maltose compound was the best.
This was tested in the capsule. The capsule containing the maltose compound and
the fluoresceine marker was applied orally and gave rise to the highest plasma
fluorescence. A solution or gelatin capsules were less effective. The capsule is a
candidate for controlled, colon-specific uptake. It should be noted that colonspecific delivery can also be accomplished by coating a capsule with pectin. This
is only dissolved in the large intestine. There are interesting possibilities in combination with chitosan.
The N-acetyl chitosans are the most interesting for controlled release.
Galactosylated chitosan microspheres have been prepared. Production of more
specific oligoglycoside-chain chitosan might develop into active targeting of specific tissues. Pectinate gel beads modified with trimethyl chitosan have been
prepared and evaluated for colon targeted delivery of macromolecules.
Chitosan beads containing prednisolone were implanted in mouse skin within
induced local inflammatory air pouches. These chitosan beads are biocompatible
and biodegradable vehicles for treatment. An effective dose can be given in
combination with prolonged periods of local drug presence. This compares advantageously with injection of a prednisolone suspension.
6.3 Chitosan Nanoparticles for Drug Delivery, Gene Therapy
and Cancer Therapy
Among the various drug delivery systems, nanoparticles have several advantages,
such as high drug encapsulation efficiency, efficient drug protection against chemical or enzymatic degradation, unique ability to create a controlled release, cell
internalization as well as the ability to reverse the multidrug resistance of tumour
cells. They could also provide one solution for delivery of new classes of active
molecules such as peptides, proteins, genes and oligonucleotides. However, the
Biopolymeric Micro- and Nanoparticles: Preparation, Characterization and. . .
289