Biomedical Engineering Reference
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Fig. 16 PEO-b-PCL-PEI micelles for plasmid DAN delivery. ( a ) Structure of PEO-PCL-PEI
micelles. ( b ) PEO-PCL-PEI/pDNA micelles ( c ) pDNA complexed PEO-PCL-PEI micelles with
a-CD to decrease the hydrogen bonding led to increased gene transfection efficiency
condensation and excellent transgene expression efficiency comparable to PEI/
DNA polyplexes but better biocompatibility and potential biodegradability but
lower cytotoxicity than PEI. However, PEO-PCL-PEI with high PEO graft den-
sity and long PCL blocks showed very poor gene expression due to hydrophobic
PCL and hydrogen bonding between PCL and PEI. Therefore, a-cyclodextrin
(a-CD) was used to break the hydrogen bonds and dissolute PCL block as well by
formation of inclusion complexes between a-CD and PCL blocks(Shuai et al.
2005 ). Addition of a-CD led to increased gene transfection efficiency and excel-
lent biocompatibility for the delivery system for in vivo use (Fig. 16c ).
Instead of introducing new cationic block or group to the end of PCL, our group
has grafted various polyamine moieties to PCL block for siRNA delivery (Xiong
et al. 2008b ). After introducing carboxylic groups to caprolactone units of PCL
block, we synthesized a novel family of PEO-PCL based polycationic copolymers,
i.e., PEO-PCL with grafted spermine (PEO-P(CL-SP)), tetraethylenepentamine
(PEO-P(CL-TP)), or N,N-dimethyldipropylenetriamine (PEO-P(CL-DP))
(Fig. 17a ). These polyamine-grafted PEO-PCL copolymers demonstrated good
compatibility and were able to effectively bind siRNA, self-assemble into micelles,
protect siRNA from degradation by nuclease and release complexed siRNA effi-
ciently in the presence of low concentrations of polyanionic heparin. siRNA formu-
lated in PEO-P(CL-SP) and PEO-P(CL-TP) micelles showed efficient cellular
uptake through endocytosis by MDA435/LCC6 cells transfected with MDR-1 gene,
which encodes for the expression of P-glycoprotein (P-gp). Importantly, the siRNA
formulated in PEO-P(CL-SP) and PEO-P(CL-TP) micelles demonstrated effective
endosomal escape after cellular uptake (Fig. 17b ). MDR1 targeted siRNA formu-
lated in PEO-P(CL-SP) and PEO-P(CL-TP) micelles exhibited efficient gene
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