Pharmaceutical Manufacturing Handbook: Production and

542 BIODEGRADABLE NANOPARTICLES
amino acids. Although cardiotoxicity and mild immunogenicity were reported with
gelatin nanoparticles covalently coupled to doxorubicin, this was attributed to the
coupling reagent glutaraldehyde [70] .
Pullulan and Dextran Nanoparticles Pullulan nanoparticles successfully delivered
HER2 oncoprotein to induce humoral and cellular immune responses against
HER2 - expressing murine sarcomas [71] . Hydrophobic polysaccharides such as pullulan
and mannan enable soluble proteins to induce cellular immunity and therefore
may be a potential delivery vehicle for vaccines [72] . pH - sensitive pullunan nanoparticles
prepared by conjugating sulfonamides are stable at physiological pH but
aggregate and release the encapsulated drug when exposed to the lower tumor pH
[73] . Coating of magnetic nanoparticles with pullulan enhanced their cellular uptake
by endocytosis [74] . Amphotericin - loaded, dextran – polyethyleneimine nanoparticles
were active against Candida albicans [27] . Similarly, insulin - containing dextran –
polyethyleneimine nanoparticles prolonged the hypoglycemic effect in diabetic
rats [75] . Hydrogels prepared from blends of polyvinyl alcohol and dextrans have
been used as matrices to entrap PLGA nanoparticles [76] . In vitro, immunofl
uorescent staining illustrated that pullulan nanoparticles are internalized by active
endocytosis [25] . However, other studies suggest that both absorption and
internalization of pullulan nanoparticles are inhibited by coating them with dextran
[77] .
Albumin Nanoparticles A signifi cant development in the drug delivery of albumin
nanoparticles has been the recent marketing of the commercial product Abraxane ®
for chemotherapy of breast cancer. This delivery system is prepared by nab TM
technology, which involves noncovalent complexation of albumin with paclitaxel.
Albumin nanoparticles have been used to deliver antisense oligonucleotides, interferon
γ , and anticytomegaloviral drugs [78, 79] . Intravitreal injection of gancicyclovir
- loaded albumin nanoparticles was attempted to prolong residence time in the
eye [79] . PLA nanoparticles coated with albumin degrade more rapidly in the gastrointestinal
(GI) region, resulting in effi cient delivery of water - soluble drugs across
the GI tract [80] . In addition, intra - arterial chemotherapy with paclitaxel - containing
albumin nanoparticles effectively treated squamous cell carcinoma [81] . Human
serum albumin – polyethyleneimine nanoparticles optimized transfection of the
luciferase gene in human, embryonic, and epithelial kidney cells [82] . Conjugation
of the cellular targeting agent, folic acid, resulted in increased cellular uptake of
albumin nanoparticles compared to unmodifi ed particles [83, 84] . Transferrin - conjugated
PEGylated albumin nanoparticles demonstrated enhanced uptake into the
brain tissues [85] . Glycyrrhizin was conjugated to the amine groups of albumin
nanoparticles targeting hepatocytes [86] . After i.v. administration, albumin - coated
PLA nanoparticles were distributed in the liver, bone marrow, lymph nodes, spleen,
and peritoneal macrophages [87] . In the body, albumin nanoparticles are actively
taken up by macrophages.
Gliadin Nanoparticles The hydrophobic nature of gliadin makes this polymer
ideal for delivery of hydrophobic compounds such as all - trans retinoic acid and
vitamin E. Gliadin nanoparticles adhered to the stomach mucosa and signifi cantly
increased the bioavailability of carbazole [88] . Typically, encapsulation effi ciency