developed that allowed pH-controlled drug release, showing drug-loaded PAC
nanoparticles to be as active as the free drug [146]. In vivo experiments with
mice have been performed to demonstrate the high efficiency of antibiotic-loaded
PACA nanoparticles for the treatment of intracellular infections [150]. Various
bioactive compounds (e.g., cytostatics, hormones, peptides, and nucleic acids) have
also been loaded into PAC nanocarriers. Although the drug-loaded nanoparticles do
not directly reach the cancer cells, the phagocytes in the organs where the
nanoparticles become entrapped may serve as drug reservoirs. In vivo studies
showed that PAC nanocapsules enhanced the accumulation of drug in the lymph
nodes compared to other carriers such as emulsions and liposomes [151]. Drugloaded PAC nanoparticles have been applied to the brain by modifying their surface
with the surfactant polysorbate 80 [152, 153]. It has been proposed that these
nanocarriers adsorb apolipoproteins E from blood plasma and then cross the brain
endothelium via receptor-mediated endocytosis and transcytosis through the endothelial cells [153]. These routes play an important role in the treatment of brain
tumors using drug-loaded PAC nanoparticles. The indomethacin inhibits the production of prostaglandin in the stomach and intestines, which maintains the mucous
lining of the gastrointestinal tract. Indomethacin has been encapsulated into poly
(isobutyl cyanoacrylate) (PIBC) nanoparticles and found to be stable for up to
12 months [154]. However, PIBC nanocapsules also showed an inhibition of
platelet aggregation because of their isobutyl cyanoacrylate content [154].
Doxorubicin-loaded poly(butyl cyanoacrylate) (PBC) nanoparticles have also
been reported to increase 60-fold in the brain after being coated with polysorbate
80 [152].
6.6 Chitosan
Chitosan is a naturally occurring biodegradable cationic polymer derived from
chitin, which is a fully acetylated polymer that is used in many biomedical
applications such as wound dressings and drug delivery vehicles [155, 156].
Chitosan is a linear polysaccharide consisting of β-(1-4)-linked D-glucosamine
with randomly located N-acetyl glucosamine groups, depending upon the degree
of deacetylation of the polymer. Chitosan is degraded by a few enzymes (such as
chitosanase, lysozyme, and papain) in vitro and is degraded and hydrolyzed into
acetylated residues by lysozyme in vivo [157]. The rate of degradation of chitosan
inversely depends on the degree of acetylation and crystallinity of the polymer
[158]. The fast degradation rate of chitosan has been attributed to the deformation
of strong hydrogen bonds present in chitosan. Due to strong positive charges on
chitosan, it can strongly interact with the negatively charged mucous membrane as
an effective mucoadhesive [159]. It can be fabricated into various devices because
of its solubility in water and can form microsphere and nanosphere formulations
without using any organic solvents, thus maintaining the immunogenicity of the
antigens [160]. Several chitosan–drug conjugates have also been used for cancer
Biodegradable Polymers for Potential Delivery Systems for Therapeutics
189
nanoparticles to be as active as the free drug [146]. In vivo experiments with
mice have been performed to demonstrate the high efficiency of antibiotic-loaded
PACA nanoparticles for the treatment of intracellular infections [150]. Various
bioactive compounds (e.g., cytostatics, hormones, peptides, and nucleic acids) have
also been loaded into PAC nanocarriers. Although the drug-loaded nanoparticles do
not directly reach the cancer cells, the phagocytes in the organs where the
nanoparticles become entrapped may serve as drug reservoirs. In vivo studies
showed that PAC nanocapsules enhanced the accumulation of drug in the lymph
nodes compared to other carriers such as emulsions and liposomes [151]. Drugloaded PAC nanoparticles have been applied to the brain by modifying their surface
with the surfactant polysorbate 80 [152, 153]. It has been proposed that these
nanocarriers adsorb apolipoproteins E from blood plasma and then cross the brain
endothelium via receptor-mediated endocytosis and transcytosis through the endothelial cells [153]. These routes play an important role in the treatment of brain
tumors using drug-loaded PAC nanoparticles. The indomethacin inhibits the production of prostaglandin in the stomach and intestines, which maintains the mucous
lining of the gastrointestinal tract. Indomethacin has been encapsulated into poly
(isobutyl cyanoacrylate) (PIBC) nanoparticles and found to be stable for up to
12 months [154]. However, PIBC nanocapsules also showed an inhibition of
platelet aggregation because of their isobutyl cyanoacrylate content [154].
Doxorubicin-loaded poly(butyl cyanoacrylate) (PBC) nanoparticles have also
been reported to increase 60-fold in the brain after being coated with polysorbate
80 [152].
6.6 Chitosan
Chitosan is a naturally occurring biodegradable cationic polymer derived from
chitin, which is a fully acetylated polymer that is used in many biomedical
applications such as wound dressings and drug delivery vehicles [155, 156].
Chitosan is a linear polysaccharide consisting of β-(1-4)-linked D-glucosamine
with randomly located N-acetyl glucosamine groups, depending upon the degree
of deacetylation of the polymer. Chitosan is degraded by a few enzymes (such as
chitosanase, lysozyme, and papain) in vitro and is degraded and hydrolyzed into
acetylated residues by lysozyme in vivo [157]. The rate of degradation of chitosan
inversely depends on the degree of acetylation and crystallinity of the polymer
[158]. The fast degradation rate of chitosan has been attributed to the deformation
of strong hydrogen bonds present in chitosan. Due to strong positive charges on
chitosan, it can strongly interact with the negatively charged mucous membrane as
an effective mucoadhesive [159]. It can be fabricated into various devices because
of its solubility in water and can form microsphere and nanosphere formulations
without using any organic solvents, thus maintaining the immunogenicity of the
antigens [160]. Several chitosan–drug conjugates have also been used for cancer
Biodegradable Polymers for Potential Delivery Systems for Therapeutics
189