Pharmaceutical Manufacturing Handbook: Production and

SYNTHETIC BIODEGRADABLE POLYMERIC NANOPARTICLES 545
prepare SLNs are triglycerides, glycerides, fatty acids, steroids, and waxes and may
contain a wide range of emulsifi ers. Methods of preparation of SLNs include high
speed hot and cold homogenization, ultrasound, emulsion – solvent evaporation, and
microemulsion. The various parameters involved in the preparation of SLNs have
been optimized and thoroughly reviewed and their physicochemical properties
elucidated [103, 104] .
Other Synthetic Biodegradable Polymers Although well investigated for drug
delivery, polyorthoesters, polyurethanes, and polyamides have found limited application
as nanoparticles. A report documents the synthesis and characterization of
polyorthoester nanoparticles [105] .
5.4.3.2 Drug Delivery Applications and Biological Fate of Synthetic
Biodegradable Polymers
PLA / PLGA Nanoparticles A wide range of hydrophilic and hydrophobic drugs,
including low - and high - molecular - weight compounds, have been encapsulated into
PLGA/PLA nanoparticles for a wide range of therapeutic applications and routes
of administration, including oral, intravenous, intra - arterial, nasal, and inhalation
delivery [92, 106] . Extensive reviews describing the application of PLGA nanoparticles
in drug therapy are available [92, 107, 108] .
After i.v. administration, the PLGA nanoparticles are removed from systemic
circulation by the mononuclear phagocytic system in the liver [109] . PLGA nanoparticles
enter cells by absorptive endocytosis and may escape the lysosomes to accumulate
in cytoplasm [110, 111] . In the body, PLA and PLGA degrade into the
monomers lactic and glycolic acids, which enter the citric acid cycle, where they are
metabolized and eliminated as CO 2 and H 2 O. Glycolic acid may also be excreted
through the kidney [91] . Humoral response to these results in mild, acute, and
chronic infl ammation [112] .
Poly( e-caprolactone) Nanoparticles As important applications of poly( ε -
caprolactone) nanoparticles have been reviewed previously, only representative
examples will be given [94] . Decreased cardiovascular adverse effects of cartelol
was observed upon ophthalmic administration of poly( ε - caprolactone) nanocapsules
[113] . Poly( ε - caprolactone) nanoparticles, nanocapsules, or nanoemulsions
increased the ocular uptake of indomethacin [114] . The cytotoxicity of retinoic acid
was enhanced when delivered in core - shell - type nanoparticles formed from poly( ε -
caprolactone – polyethylene glycol) blends [115] . Alternately, these nanoparticles
were also chemically modifi ed with folic acid to target the folate receptors for
enhanced cellular uptake [116] . Coating poly( ε - caprolactone) nanoparticles with
polysaccharides such as galactose resulted in lectin - dependent aggregation, demonstrating
the potential as a targeted delivery system to hepatocytes [117] . Stable
complexes were formed between anionic DNA and chitosan - modifi ed poly( ε -
caprolactone) nanoparticles, demonstrating high transfection effi ciency [118] . After
i.v. administration, these particles are eliminated by macrophages of the reticuloendothelial
system and biodegradation occurs by bulk scission of polymer chains
[94] . However, dextran - coated poly( ε - caprolactone) nanoparticles lowered their
uptake into macrophages [119] .