Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 143; pp. 406 - 414
• Main Authors: Ilbasmis-Tamer, Sibel, Unsal, Hande, Tugcu-Demiroz, Fatmanur, Kalaycioglu, Gokce Dicle, Degim, Ismail Tuncer, Aydogan, Nihal
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2016
• Subjects: Acrylic Resins - chemistry; Alginates - chemistry; Animals; Anthraquinone; Anthraquinones - chemistry; Antibiotics, Antineoplastic - chemistry; Antibiotics, Antineoplastic - pharmacology; Cell Line; Chitosan; Chitosan - chemistry; Colon - drug effects; Colon - metabolism; Colorectal cancer; Diffusion Chambers, Culture; Doxorubicin; Doxorubicin - chemistry; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug Compounding; Drug delivery; Drug delivery systems; Drug Liberation; Drug loading; Drugs; Fibroblasts - cytology; Fibroblasts - drug effects; Glucuronic Acid - chemistry; Hexuronic Acids - chemistry; Humans; Hydrogen-Ion Concentration; Hypromellose Derivatives - chemistry; Kinetics; Lipid nanotube; Lipids; MCF-7 Cells; Membranes, Artificial; Mice; Molecular structure; Nanotubes; Nanotubes - chemistry; Nanotubes - ultrastructure; Sheep; Drug delivery; Anthraquinone; Drug loading; Lipid nanotube; Doxorubicin; Colorectal cancer
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2016.03.070

The new pH-sensitive AQUA lipid nanotubes (LNTs) are candidates for delivery agents for the colonic administration of doxorubicin for colorectal cancer treatment. [Display omitted] •Biocompatible, stable and non-toxic new lipid nanotube-based delivery systems (LNTs) have been developed.•DOX-loaded LNTs are distributed in gel formulations to be used for the treatment of colorectal cancer (CRC).•DOX loading increased with increasing pH of the medium and reached its maximum value (96%) at pH 9.0.•DOX release was higher at lower pHs, and the best result was obtained with chitosan used as the gel. Lipid nanotubes (LNTs) are one of the most advantageous structures for drug delivery and targeting. LNTs formed by a specially designed molecule called AQUA (AQ-NH-(CH2)10COOH (AQ: anthraquinone group) is used for drug delivery, and doxorubicin (DOX) is the drug selected. DOX and AQUA have some similarities in their molecular structures, so a significant amount of DOX can be loaded to LNTs. The AQUA LNTs are pH responsive, and drug loading increased almost linearly by increasing the pH, reaching a maximum value (96%) at pH 9.0. In terms of drug release, lower pHs are preferred. Drug-loaded LNTs are also mixed with four different gels (chitosan, alginate, hydroxypropyl methylcellulose and polycarbophil) to use the advantages of these gels. The drug release efficiency is studied using a Franz diffusion cell in which sheep colon membranes and dialysis membranes are utilized. The amount of released DOX from the chitosan gel formulations was quite high. Sodium alginate gels had lower release and slower diffusion of DOX. The cytotoxic effect of DOX-loaded AQUA LNTs has also been determined on cell cultures. Our new lipid nanotubes are a non-toxic, effective, biodegradable, biocompatible, stable and promising system for drug delivery and can be used for colonic administration of DOX for the treatment of colorectal cancer (CRC).