Biomedical Engineering Reference
In-Depth Information
A), and griseofulvin (GRF) by encapsulating in PMBs and the safeness of oral
administration to rats.
44
However, the accumulation of nonbiodegradable polymers, such as PTX-
PMB30W, in cells is always a concern in the application of nanomedicine.
Biodegradable polymers are much desired. In general, biodegradable polymers
represented by poly(
L
-lactic acid) (PLA) and poly(e-caprolactone) (PCL) have
been used as the materials for making nanoparticles. However, as conventional
PLA nanoparticles contact with the blood components after injection into the
blood stream, the plasma proteins are immediately adsorbed on the PLA
nanoparticles and a conformational change of adsorbed protein is induced.
45,46
Konno et al.
47
prepared PMB/PLA nanoparticles by a solvent evaporation
technique from oil in water systems using the water-soluble amphiphilic
phospholipid polymer PMB as both emulsifier and surface modifier. The
phospholipid polymer on the nanoparticles effectively suppressed any
unfavorable interactions with the biocomponents and improved the blood
compatibility of the conventional PLA nanoparticles. Hsiue et al.
48
prepared
PMPC-b-PLA polymeric nanoparticles, and the low cytotoxicity of the
polymer nanoparticles was confirmed by cytotoxicity assay and growth
inhibition assays with HFW (human fibroblast cell), indicating good
cytocompatibility of the lipid-like diblock copolymer PMPC-b-PLA. Liu
et al.
49
also demonstrated that PMPC-b-PLA could form micelles in aqueous
solution. The micelles displayed excellent biocompatibility and a high drug-
loading efficiency. In vitro release profiles indicated that the PMPC-b-PLA
micelles could be used for the administration of controlled-release hydro-
phobic anticancer drugs. Tu et al.
50
prepared novel star-shaped copolymers
having six-arm stars with a zwitterionic PC block copolymer, poly(e-
caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine) (6sPCL-b-
PMPC). The micelles with PC groups expressed at their exterior showed
excellent internalization ability into cancer cells. When incorporated with
PTX, the 6sPCL-b-PMPC micelles show much higher cytotoxicity against
HeLa cells than PCL-b-PEG micelles, in response to the higher efficiency of
cellular uptake. Cooper et al.
51
presented the synthesis of water-soluble,
biodegradable, zwitterionic aliphatic polyesters using ring-opening polymer-
ization and post click chemistry with PC azide, giving materials with potential
applications that benefit from a combination of biodegradability, biocompat-
ibility, and water solubility (Figure 10.2). Iwasaki et al.
52
synthesized
biodegradable polyphosphate graft copolymers with varying densities of
cholesteryl esters and hydrophilic MPC graft chains as novel amphiphilic
biomaterials. The graft polymers containing cholesteryl groups effectively
enhanced the solubility of PTX in an aqueous solution.
In most cases, the encapsulated chemotherapeutic drugs show a burst release
up to 20-30% within several hours post-micelle formation, followed by a slow
diffusional drug release lasting for many days. The premature burst release
leads to drug loss in micelle storage and blood circulation, which also limits the
total applicable dose caused by immediate toxicity after injection. Meanwhile,
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