Pharmaceutical Manufacturing Handbook: Production and

NATURAL BIODEGRADABLE POLYMERIC NANOPARTICLES 541
ovalbumin [40] . A study reported that chitosan - stabilized alginate nanoparticles
increased bioavailability and sustained release of antifungal drugs compared to
PLGA nanoparticles [41] . Although predominantly used for oral administration,
inhaled alginate nanoparticles improved the bioavailability of antitubercular drugs
[42] . In vivo, alginate nanoparticles accumulate in the Kupffer cells, parenchymal
cells of liver, and phagocytes of spleen and lungs [43, 44] . Alginate nanoparticles
have also been reported to be absorbed into Peyer ’ s patches, suggesting that they
may enhance targeting to the intestinal mucosa [45] . In the body, the alginates
degrade by acidic hydrolysis of the guluronic and mannuronic segments [46] .
Chitosan Nanoparticles In addition to low - molecular - weight drugs and nutraceuticals,
chitosan nanoparticles are widely used in the delivery of macromolecules such
as DNA and small interfering ribonucleic acid (siRNA) [47] . Apart from sustaining
the release of macromolecules, chitosan nanoparticles protect them from nucleases.
Placebo chitosan nanoparticles exhibited antibacterial activity against several
microbes, including Escherichia coli [48] . The surface of chitosan nanoparticles was
hydrophobically modifi ed with linoleic acid for delivery of trypsin [49] . Other applications
of chitosan nanoparticles include lung [50] and ocular delivery [51] . The
primary amine group at the 2 position can be modifi ed to tailor chitosan for specifi c
applications. For example, chemical conjugation of these amine groups to methoxy -
PEG groups increased water solubility [52] . Thiolation of chitosan enhanced the
mucosal permeation of the nanoparticles [53] . Hydrophobically modifi ed glycol
chitosans that self - assemble into nanoparticles have been used to deliver doxorubicin
[54] . Targeting chitosan nanoparticles to folate receptors on the surface of cells
enhanced the transfection effi ciency of DNA [55] . N - Succinyl chitosan nanoparticles
containing 5 - fl uorouracil demonstrated excellent activity against sarcoma tumors
[56] . Self - assembled N - acetyl histidine – conjugated glycol chitosan nanoparticles
were effi ciently internalized into cells by adsorptive endocytosis [57] . No toxic
effects have been observed with chitosan nanoparticles. Upon intravenous (i.v.)
administration, chitosan nanoparticles accumulated in the liver with minimal concentrations
in the heart and lung [54] .
Gelatin Nanoparticles Gelatin nanoparticles have been used as a delivery system
for several drugs, including pilocarpine, hydrocortisone [58] , methotrexate [59] ,
paclitaxel [60] , and chloroquine [61] . High protein loading and sustained release
were achieved using composite gelatin and PLGA nanoparticles [62] . Surprisingly,
placebo gelatin nanoparticles exhibited antimelanoma activity in vivo [63] . Primary
amine groups of gelatin molecule can be chemically conjugated or cross - linked using
bifunctional cross - linkers. This is demonstrated in the delivery of biotinylated
peptide nucleic acid using avidin - cross - linked gelatin nanoparticles [64] . PEGylation
of gelatin nanoparticles containing hydrophilic drugs prolonged circulation time in
the body [65] . Thiolated gelatin nanoparticles produced effective transfection of
plasmid DNA encoding the green fl uorescent protein [66] . Following endocytic
uptake by the cells, gelatin nanoparticles concentrate in the perinuclear region [65] .
In vitro, the gelatin nanoparticles are effi ciently internalized into macrophages and
monocytes [67] . In tumor - bearing mice, PEGylated gelatin nanoparticles predominantly
accumulated in the liver and tumor [68] while in dendritic cells they are primarily
localized in the lysosomes [69] . In vivo, gelatin is degraded by proteases to