Surface density of polyarginine influence the size, zeta potential, cellular uptake and tissue distribution of the nanostructured lipid carrier.
Poly-arginines are strong tools to elevate the cellular uptake of nanopreparations. To learn the influence of poly-arginine (RRRRRRRR, R8) density on a series of properties of nanostructured lipid carrier (NLC), we build six R8 modified NLCs with different R8 densities (nR-NLC, where n represents the R8 ratio) by fusion-emulsion method with the aid of stearyl-R8. The pharmaceutical characteristics like size, zeta potential and in vitro drug release, cellular uptake, cytotoxicity to A549 cells and tissue distribution in S180 tumor-bearing mice of the six nR-NLCs are all investigated. It turns out that with as little as 2% weight ratio of stearyl-R8 modified on NLC, its pharmaceutical properties, especially zeta potential changes astonishingly; however, the stearyl-R8 ratio should be higher than 4% to upgrade the cellular uptake and cytotoxicity evidently; in the ex vivo tissue distribution assessment, the nR-NLC with less than 8% R8 showed similar tissue accumulation, while NLC with 10% R8 shows obvious acute toxicity to mice. Our study pays attention to the effect of the R8 ratio on the changes of cargo properties, and the results indicate that this topic is essential and worth to be further developed.
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Mingshuang
M
Sun
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Zhihong
Z
Zhu
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Huixin
H
Wang
b School of Pharmacy, Qiqihar Medical University , Qiqihar , China , and.
Cuiyan
C
Han
c School of Biomedical & Chemical Engineering, Liaoning Institute of Science and Technology , Benxi , China.
Dandan
D
Liu
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Lei
L
Tian
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Xinggang
X
Yang
a School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China.
Weisan
W
Pan
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D007275:Injections, Intravenous; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D015394:Molecular Structure; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D010316:Particle Size; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D010455:Peptides; C015462:polyarginine; D017239:Paclitaxel
Poly-arginine; cellular uptake; nanostructured lipid carriers; surface density; tissue distribution