Pharmaceutical Manufacturing Handbook: Production and

APPLICATIONS OF BIODEGRADABLE NANOPARTICLES 547
129 – 131] . Interestingly, when heated above the LCST, poly(NIPAAm) – PEG block
copolymers spontaneously self - assemble into nanoparticles whose size is controlled
by the rate of heating [132] .
pH-Sensitive Polymeric Nanoparticles Enteric - coated polymers have long been
used to protect drugs from the acidic pH in the stomach. Chitosan is a pH - sensitive
polymer that is soluble only in acidic media. Similarly, the solubility of sulfonamide -
modifi ed pullulans is dependent on pH [133] . Chitosan – insulin nanoparticles are
stable at low pH but dissociate at physiological pH, releasing insulin [134] . The pH
of tumor interstitium is lower than the normal tissue. The pH - sensitive polyethylene
oxide – poly( β - amino ester) microparticles containing paclitaxel signifi cantly reduced
tumor burden [135, 136] . Polyketals, a new generation of acid - sensitive polymers,
degrade by acidic hydrolysis [137] . Low pH inside the endosomes facilitated the
escape of pH - responsive plasmid – lipid nanoparticles, resulting in enhanced transfection
effi ciency [138] .
5.4.4.2 Drug Delivery Applications and Biological Fate of Thermosensitive and
p H - Sensitive Nanoparticles
Thermosensitive block copolymer nanoparticles containing doxorubicin increased
cytotoxicity against Lewis lung carcinoma cells when activated by heating above
the LCST [139] . Chitosan was chemically conjugated to NIPAAm/vinyl laurate
copolymer to enhance gene transfection in mouse myoblast cells [140] . Upon i.v.
administration, poly(NIPAAm) nanoparticles are taken up by the reticuloendothelial
cells of the liver and mild infl ammatory and fi brotic responses are observed
[141] .
After internalization into SKOV - 3 (ovarian adenocarcinoma) cells, polyethylene
oxide – modifi ed poly( β - amino ester) nanoparticles rapidly disintegrated and released
the drug in the low pH of the endosomes [142] . Intravenous administration of polyethylene
oxide – modifi ed poly( β - amino ester) nanoparticles containing paclitaxel
signifi cantly reduced tumor burden in mice with ovarian cancer [142] . N - Acetyl
histidine – conjugated glycol chitosan nanoparticles were used to deliver drugs into
the cytoplasm. These pH - responsive nanoparticles are endocytosed where their
structural integrity is lost due to protonation of imidazoles, resulting in their endo -
lysosomal escape [57] . As most of the pH - sensitive biodegradable polymers are
blends of natural and synthetic polymers, they are degraded by mechanisms specifi c
to individual polymers.
5.4.5 APPLICATIONS OF BIODEGRADABLE NANOPARTICLES
OTHER THAN DRUG DELIVERY
Diagnosis and imaging are important applications of nanoparticles that are briefl y
described. The ability to encapsulate or conjugate fl uorescent compounds into or
onto biodegradable nanoparticles has been used extensively in imaging. Compounds
that have been encapsulated into nanoparticles for imaging include gadolinium,
fl uorescein isothiocyanate (FITC) – dextrans, Bodipy, and the autofl uorescent anticancer
drug doxorubicin. Nanoparticles encapsulating radioactive ligands, such as