PCM and TAT co-modified liposome with improved myocardium delivery: in vitro and in vivo evaluations.
In this study, PCM and TAT co-modified liposome was developed as a novel drug carrier for myocardium delivery with evaluation of its in vitro and in vivo properties. Liposomes containing fluorescent probe coumarin-6 were prepared by thin-film hydration. The PCM ligands specifically bind to the PCM receptors in the extracellular connective tissue of primary myocardium cells (MCs), while the TAT ligands functioned as a classical cell penetrating peptide to make liposomes internalized by MCs. The unmodified liposome (L), PCM-modified liposome (PL), TAT-modified liposome (TL) and PCM and TAT co-modified liposome (PTL) were prepared and characterized. The cellular uptake and intracellular distribution of various liposomes by MCs demonstrated that PTL had the best delivery capability. Peptide inhibition assay indicated that the uptake of PL could be inhibited by PCM. However, TAT could almost not suppress the uptake of TL. In addition, the CCK-8 experiments showed that liposomes had low cytotoxicity. In vivo fluorescent images of frozen sections and HPLC-fluorescence analysis further demonstrated that PTL had highest myocardium distribution. The results of this study demonstrated that PCM and TAT co-modifying could improve the myocardial targeting ability of liposome.
a Department of pharmaceutics , School of Pharmacy, Chongqing Medical University , Chongqing , P. R. China and.|b Chongqing Research Center for Pharmaceutical Engineering , Chongqing , P. R. China.
Xin
X
Wang
a Department of pharmaceutics , School of Pharmacy, Chongqing Medical University , Chongqing , P. R. China and.|b Chongqing Research Center for Pharmaceutical Engineering , Chongqing , P. R. China.
Hua
H
Huang
a Department of pharmaceutics , School of Pharmacy, Chongqing Medical University , Chongqing , P. R. China and.|b Chongqing Research Center for Pharmaceutical Engineering , Chongqing , P. R. China.
Liangke
L
Zhang
a Department of pharmaceutics , School of Pharmacy, Chongqing Medical University , Chongqing , P. R. China and.|b Chongqing Research Center for Pharmaceutical Engineering , Chongqing , P. R. China.
Yan
Y
Bai
a Department of pharmaceutics , School of Pharmacy, Chongqing Medical University , Chongqing , P. R. China and.|b Chongqing Research Center for Pharmaceutical Engineering , Chongqing , P. R. China.
Huali
H
Chen
D000595:Amino Acid Sequence; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D008081:Liposomes; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D008081:Liposomes; D010446:Peptide Fragments
PCM; TAT; co-modified; coumarin-6; myocardium delivery