Short Peptide-Mediated Brain-Targeted Drug Delivery
with Enhanced Immunocompatibility
Posted on 2019-01-18 - 21:19
Peptide ligands have
been exploited as versatile tools to facilitate
targeted delivery of nanocarriers. However, the effects of peptide
ligands on immunocompatibility and therapeutic efficacy of liposomes
remain intricate. Here, a short and stable brain targeted peptide
ligand D8 was modified on the surface of doxorubicin-loaded liposomes
(D8-sLip/DOX), demonstrating prolonged blood circulation and lower
liver distribution in comparison to the long and stable D-peptide
ligand DCDX-modified doxorubicin-loaded liposomes (DCDX-sLip/DOX) by mitigating natural IgM absorption. Despite
the improved pharmacokinetic profiles, D8-sLip/DOX exhibited comparable
brain targeting capacity in ICR mice and antiglioblastoma efficacy
to DCDX-sLip/DOX in nude mice bearing intracranial glioblastoma.
However, dramatic accumulation of DCDX-sLip/DOX in liver
(especially during the first 8 h after intravenous injection) resulted
in pathological symptoms, including nuclei swelling, necrosis of liver
cells, and inflammation. These results suggest that short peptide
ligand-mediated brain-targeted drug delivery systems possessing enhanced
immunocompatibility are promising to facilitate efficient brain transport
with improved biosafety.
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Guan, Juan; Jiang, Zhuxuan; Wang, Mengke; Liu, Ying; Liu, Jican; Yang, Yang; et al. (2019). Short Peptide-Mediated Brain-Targeted Drug Delivery
with Enhanced Immunocompatibility. ACS Publications. Collection. https://doi.org/10.1021/acs.molpharmaceut.8b01216
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AUTHORS (11)
JG
Juan Guan
ZJ
Zhuxuan Jiang
MW
Mengke Wang
YL
Ying Liu
JL
Jican Liu
YY
Yang Yang
TD
Tianhao Ding
WL
Weiyue Lu
CG
Chunli Gao
JQ
Jun Qian
CZ
Changyou Zhan