Biomedical Engineering Reference
In-Depth Information
TAX and dox have been encapsulated in polymersomes for passive delivery
to tumor-bearing mice. 167 The big molecules that compose the polymersome
are used to embed the water-insoluble TAX within the NM shell. Unlike TAX,
dox is water soluble and stays within the interior of the polymersome until it
degrades. When the drugs are combined with the polymersome, they spontane-
ously self-assemble into a cocktail that lead to better tumor regression than
either drugs alone. Furthermore, the polymersome drug cocktail carries both
drugs efficiently to a tumor.
5.9.2   Micelles
Block copolymer micelles are spherical supermolecular assemblies of amphiphilic
copolymer in which the core can accommodate hydrophobic drugs while the shell
is a hydrophilic brush-like corona that makes the micelle water soluble, allowing
delivery of the poorly soluble contents. 1 Camptothecin (CPT) is a topoisomer-
ase I inhibitor that is effective against cancer but has poor solubility, instability,
and toxicity limiting its clinical application. To solve these issues, biocompatible,
targeted sterically stabilized micelles (SSMs) have been used as nanocarriers for
CPT (CPT-SSM). SSM solubilization of CPT is expensive yet reproducible and
it prevents drug aggregate formation. In addition, SSM composed of PEGylated
phospholipids are attractive nanocarriers for CPT delivery because of their size
(14 nm) and ability to extravasate through the leaky microvasculature of tumors
and inflamed tissues. This passive targeting results in high drug concentration in
tumors and reduced drug toxicity to the normal tissues. 168 Stealth micelle formu-
lations have stabilizing PEG coronas to minimize opsonization of the micelles
and maximize serum half-life. Currently, SP1049C, NK911, and Genexol-PM
have been approved for clinical use. 42 SP1049C is formulated as dox-encapsulated
pluronic micelles. NK911 is dox-encapsulated micelles from a copolymer of
PEG-dox-conjugated poly(aspartic acid), and Genexol-PM is a TAX-encapsulated
PEG-PLA micelle formulation. Polymer micelles have several advantages over
other drug delivery systems, including increased drug solubility, prolonged cir-
culation half-life, selective accumulation at tumor sites, and lower toxicity. How-
ever, this technology currently lacks tumor specificity and the ability to control
the release of the entrapped agents. With these limitations, nano-enabled therapy
has shifted focus from passive targeting systems (e.g. micelles) to active targeting.
5.9.3   Hydrogels
Hydrogel NPs use hydrophobic polysaccharides for encapsulation and delivery
of drugs, therapeutic proteins, or vaccine antigens. 1 A system using cholesterol
to form a self-aggregating hydrophobic core resulting in cholesterol NPs stabi-
lized entrapped proteins. These particles stimulate the immune system and are
readily taken up by dendritic cells. Larger hydrogel NMs can also be used to
encapsulate and release monoclonal antibodies.
Search WWH ::




Custom Search