Studies on PEG-modified SLNs loading vinorelbine bitartrate (I): preparation and evaluation in vitro.
In this study, the conjugate of PEG2000-stearic acid (PEG2000-SA) was used to prepare PEGylated solid lipid nanoparticles loading vinorelbine bitartrate (VB-pSLNs) by cold homogenization technique. The particle size and zeta potential of resulted VB-pSLNs ranged 180-250nm and 0-10mV, which were determined using a Zetasizer, respectively. Although the drug entrapment efficiency (EE) slightly decreased after the PEG modification of VB-SLNs, above 60 % EE could be reached. The drug release tests in vitro indicated the faster drug release from VB-pSLNs than that from VB-SLNs without PEG modification. To investigate the cellular uptake of VB-pSLNs, the chemical conjugate of octadecylamine-fluorescein isothiocynate (FITC-ODA) was synthesized, and was used as a fluorescence marker to incorporate into nanoparticles. The results from cellular uptake indicated that the phagocytosis of VB-pSLNs by RAW264.7 cells was inhibited effectively by the PEG modification of SLNs, while the uptake by cancer cells (MCF-7 and A549) could be improved significantly. The assay of anticancer activity in vitro demonstrated that the anticancer activity of VB was significantly enhanced by the encapsulation of SLNs and pSLNs due to the increased cellular internalization of drug. The results suggested that SLNs and pSLNs could be excellent carrier candidates to entrap VB for tumor chemotherapeutics.
Wan
Feng
F
College of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, PR China.
You
Jian
J
Sun
Yu
Y
Zhang
Xing-Guo
XG
Cui
Fu-De
FD
Du
Yong-Zhong
YZ
Yuan
Hong
H
Hu
Fu-Qiang
FQ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D013229:Stearic Acids; D011092:Polyethylene Glycols; C031183:stearic acid; D014747:Vinblastine; D000077235:Vinorelbine