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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: J Pharm Investig. 2017 Dec 12;48(1):89–111. doi: 10.1007/s40005-017-0374-0

Table 2.

Identification and application of BBB shuttle peptides identified from phage display library

Peptide Sequence (phage displayed library) BBB model (in vitro and in vivo) Transport mechanism Sanger/(NGS) Advanced application– (Nano formulations) References
SGV SGVYKVAYDWQH
(Ph.D.™-12 Phage Display)
Co-cultured Endothelial cells and pericytes N.A. Sanger (31 clones) N.D. (Díaz-Perlas et al. 2016; Sánchez-Navarro et al. 2017)
Peptide-22 Ac-[cMPRLRGC]c-NH2
(15-mer cyclic phage library)
CHO cells (h LDLR +) LDLR-RMT N.A. PEG-PLA-peptide22-PTX; PEG-LIP-Peptide22-RGD-DOX. (Malcor et al. 2012; Zhang et al. 2013a; Chen et al. 2017)
B6, B8 B6: GHKAKGPRK
B8: KWKTPKVRV
(custom phage-display 9 mer library)
Purified extracellular domain of hTfR TfR-RMT Sanger (43 clones) N.D. (Xia et al. 2000)
T7 or HAI HAIYPRH
(Ph.D.™-7 Phage display Peptide Library)
CEF (hTfR +) TfR-RMT Sanger (9 clones from 10th round) PEG-LIP-T7-TAT-DOX; PEG-LIP-T7-ZL006; PEG-PLGA-T7-BCNU; PEG-PLGA-T7-PTX-BCNU; PEG-LIP-T7-DOX-VCR. Lee et al. 2001; Zong et al. 2014; Wang et al. 2015b; Bi et al. 2016; Cui et al. 2016; Zhang et al. 2017)
THR THRPPMWSPVWP
(Ph.D.™-12 Phage Display)
CEF (hTfR +) TfR-RMT Sanger (9 clones from 7th round) 68Ga-THR fallypride-THR (Lee et al. 2001; Wängler et al. 2011)
G23 HLNILSTLWKYRC
(Ph.D.™-12 Phage Display)
Immobilized ganglioside GM1 GM1/GT1b-RMT Sanger (N.A.) G23fluor polymersomes (Georgieva et al. 2012)
PepC7 CTSTSAPYC
(Ph.D.™-C7C Phage Display)
ICR mice N.D. Sanger (12 clones) N.D. (Li et al. 2012)
CRT CRTIGPSVC
(Ph.D.™-C7C Phage Display)
BALB/c mice (i.v. tail vein) TfR-RMT Sanger PEG-PLGA-CRT-PTX (Staquicini et al. 2011; Kang et al. 2015)
GLA GYR GLAHSFSDFARDFVA
GYRPVHNIRGHWAPG
(Filamentous f3-15mer)
C57Bl/6 mice (In situ Perfusion) N.D. Sanger (17 clones) P3-GLA-LIP (Van Rooy et al. 2010, 2012)
TGN TGNYKALHPHNG
(Ph.D.™-12 Phage Display)
ICR mice N.D. Sanger (20 clones) PEG-PLA-TGN; PEG-PLGA-TGN; PEG-PLA-LIP-TGN-PTX (Li et al. 2011, 2013, Gao et al. 2012, 2014, Zhang et al. 2013b, 2014; Ma et al. 2014)
c-SxTSSTx-c C-SYTSSTM-C
(Ph.D.™-C7C PhageP
Sprague-Dawley (SD) rats N.D. Sanger (500 clones) N.D (Smith et al. 2012)
CAGALCY CAGALCY
(T7-select-415-CX10 C)
6 Balb/C mice N.D. Sanger (200 clones) CAGALCY-AgNP (Fan et al. 2007; Toome et al. 2017)
#2077 RLSSVDSDLSGC
(T7-select 10-3b-12 mer)
Wistar rats N.D. NGS N.D. (Urich et al. 2015)