Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs

被引：105

作者：

Fan, Tingting ^{[1
]}

Chen, Chunhui ^{[1
]}

Guo, Han ^{[1
]}

Xu, Juan ^{[1
]}

Zhang, Jian ^{[1
]}

Zhu, Xi ^{[1
]}

Yang, Yang ^{[1
]}

Zhou, Zhou ^{[1
]}

Li, Lian ^{[1
]}

Huang, Yuan ^{[1
]}

机构：

[1] Sichuan Univ, West China Sch Pharm, Key Lab Drug Targeting & Drug Delivery Syst, Minist Educ, Chengdu 610041, Peoples R China

来源：

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS | 2014年 / 88卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Solid lipid nanoparticles; Salmon calcitonin; CSKSSDYQC peptide; IRQRRRR peptide; Caco-2/HT29-MTX co-cultured cells; Ussing chamber; Absolute bioavailability; Relative pharmacodynamic bioavailability; SALMON-CALCITONIN SCT; IN-VIVO EVALUATION; CERVICAL-MUCUS; CELL-LINES; POLYMERIC NANOPARTICLES; INTRACELLULAR DELIVERY; GENE-TRANSFER; INSULIN; TRANSPORT; VITRO;

D O I：

10.1016/j.ejpb.2014.06.011

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

Designing feasible and effective peptide ligand modified solid lipid nanoparticles (SLNs) to improve oral bioavailability of protein drugs and evaluating the influence of mucus remains important. In the present work, two kinds of peptide ligand modified SLNs loaded with salmon calcitonin (sCT), namely, sCT CSK-SLNs and sCT IRQ-SLNs, were prepared by coupling the peptide ligand CSKSSDYQC (CSK) which was reported to show affinity with goblet cells, or IRQRRRR (IRQ), a cell penetrating peptide, to polyoxyethylene (40) stearate (SA-PEC2000). Compared with unmodified SLNs, CSK or IRQ modified SLNs with better drug protection ability could facilitate the internalization of drug on Caco-2/HT29-MTX co-cultured cells and permeation in excised rat duodenum mucosa. The internalization mechanism of two kinds of peptide ligand modified SLNs was mainly active transport via both clathrin- and caveolae-dependent endocytosis. Although mucus was an impediment to the transport of SLNs, the peptide ligand modified SLNs still showed improved drug absorption. The absolute bioavailability of sCT CSK-SLNs (12.41 +/- 3.65%) and sCT IRQ-SLNs (10.05 +/- 5.10%) raised to 2.45-fold and 1.98-fold compared with unmodified SLNs (5.07 +/- 0.54%), implying the feasibility and effectiveness of CSK and IRQ peptide modification for the enhancement of the oral bioavailability of protein drugs. In summary, the nanoparticles modified with CSK or IRQ peptide ligand could be the potential carriers for the transport of protein drugs across intestinal barriers. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：518 / 528

页数：11

共 51 条

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