Sodium Dodecyl Sulfate-Modified Doxorubicin-Loaded Chitosan-Lipid Nanocarrier with Multi Polysaccharide-Lecithin Nanoarchitecture for Augmented Bioavailability and Stability of Oral Administration In Vitro and In Vivo.
For oral anti-cancer drug delivery, a new chitosan-lipid nanoparticle with sodium dodecyl sulfate modification was designed and synthesized using a double emulsification. TEM examination showed that the DOX-loaded nanoparticles, termed D-PL/TG NPs, exhibited a unique core-shell configuration composed of multiple amphiphilic chitosan-lecithin reverse micelles as the core and a triglyceride shell as a physical barrier to improve the encapsulation efficiency and reduce the drug leakage. In addition, the D-PL/TG NPs with sodium dodecyl sulfate modification on the surface have enhanced stability in the GI tract and increased oral bioavailability of doxorubicin. In vitro transport studies performed on Caco-2 monolayers indicated that the D-PL/TG NPs enhanced the permeability of DOX in the Caco-2 monolayers by altering the transport pathway from passive diffusion to transcytosis. The in vivo intestinal absorption assay suggested that the D-PL/TG NPs were preferentially absorbed through the specialized membranous epithelial cells (M cells) of the Peyer's patches, resulting in a significant improvement (8-fold) in oral bioavailability compared to that of free DOX. The experimental outcomes in this work demonstrate that the D-PL/TG NPs provide an exciting opportunity for advances in the oral administration of drugs with poor bioavailability that are usually used in treating tough and chronic diseases.
Chia-Wei
CW
Su
Min-Yu
MY
Chiang
Yu-Ling
YL
Lin
Nu-Man
NM
Tsai
Yen-Po
YP
Chen
Wei-Ming
WM
Li
Chin-Hao
CH
Hsu
San-Yuan
SY
Chen
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001826:Body Fluids / Q000187:drug effects; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D054709:Lecithins / Q000737:chemistry*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011134:Polysaccharides / Q000737:chemistry*; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry*; D055672:Static Electricity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004337:Drug Carriers; D054709:Lecithins; D011134:Polysaccharides; D012967:Sodium Dodecyl Sulfate; D004317:Doxorubicin; D048271:Chitosan