title: Design and evaluation of solid lipid nanoparticles modified with peptide ligand for oral delivery of protein drugs.
abstract: 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-PEG2000). 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.
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Tingting
authors: T
authors: Fan
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Chunhui
authors: C
authors: Chen
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Han
authors: H
authors: Guo
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Juan
authors: J
authors: Xu
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Jian
authors: J
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Xi
authors: X
authors: Zhu
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Yang
authors: Y
authors: Yang
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Zhou
authors: Z
authors: Zhou
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China.
authors: Lian
authors: L
authors: Li
authors: Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, PR China. Electronic address: huangyuan0@163.com.
authors: Yuan
authors: Y
authors: Huang
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004337:Drug Carriers; D006801:Humans; D008024:Ligands; D008055:Lipids / Q000737:chemistry*; D053758:Nanoparticles; D010455:Peptides / Q000737:chemistry*; D051381:Rats
chemical_list: D004337:Drug Carriers; D008024:Ligands; D008055:Lipids; D010455:Peptides
keywords: Absolute bioavailability; CSKSSDYQC peptide; Caco-2/HT29-MTX co-cultured cells; IRQRRRR peptide; Relative pharmacodynamic bioavailability; Salmon calcitonin; Salmon calcitonin (PubChem CID: 16129616); Solid lipid nanoparticles; Stearic acid (PubChem CID: 5281); Tripalmitin (PubChem CID: 11147); Ussing chamber