Browsing by Author "Yen, Ching-Shu"

Now showing 1 - 1 of 1

Multistage Continuous Targeting with Quantitatively Controlled Peptides on Chitosan-Lipid Nanoparticles with Multicore-Shell Nanoarchitecture for Enhanced Orally Administrated Anticancer In Vitro and In Vivo
(2017-02-01)
Su, Chia-Wei
;
Yen, Ching-Shu
;
Chiang, Chih-Sheng
;
Hsu, Chin-Hao
;
Chen, San-Yuan
A DOX-loaded polysaccharide-lecithin reverse micelles triglyceride-based oral delivery nanocarrier (D-PL/TG NPs) conjugated with (i) RGD peptide for targeting to beta 1 integrin of M cells and (ii) Lyp-1 peptide for targeting to the p32 receptor of MDA-MB-231 cells is used to investigate the multistage continuous targeting capabilities of these peptide-conjugated nanocarriers (GLD-PL/TG NPs) for tumor therapy. Variations in the targeting efficacy and pharmacokinetic properties are investigated by quantitatively controlling the surface density of different peptides on the nanoparticles. In vitro permeability in a human follicle-associated epithelium model and cytotoxicity against MDA-MB-231 cells indicate that the nanocarriers conjugated with high RGD peptide concentrations display a higher permeability due to the existence of M cells with higher transcytosis activity, but a higher concentration of conjugated Lyp-1 peptide exhibits the lowest cell viability. Being benefited from specific targeting of peptide conjugation, improved bioavailability and enhanced tumor accumulation are achieved by the GLD-PL/TG NPs, leading to better antitumor efficacy. The results of in vivo biodistribution and antitumor studies reveal that the effect of LyP-1 peptide is more predominant than that of RGD peptide. This proof of multistage continuous targeting may open the door to a new generation of oral drug delivery systems in targeted cancer therapy.