title: Nanoparticle-stabilized liposomes for pH-responsive gastric drug delivery.
abstract: We report a novel pH-responsive gold nanoparticle-stabilized liposome system for gastric antimicrobial delivery. By adsorbing small chitosan-modified gold nanoparticles (diameter ~10 nm) onto the outer surface of negatively charged phospholipid liposomes (diameter ~75 nm), we show that at gastric pH the liposomes have excellent stability with limited fusion ability and negligible cargo releases. However, when the stabilized liposomes are present in an environment with neutral pH, the gold stabilizers detach from the liposomes, resulting in free liposomes that can actively fuse with bacterial membranes. Using Helicobacter pylori as a model bacterium and doxycycline as a model antibiotic, we demonstrate such pH-responsive fusion activity and drug release profile of the nanoparticle-stabilized liposomes. Particularly, at neutral pH the gold nanoparticles detach, and thus the doxycycline-loaded liposomes rapidly fuse with bacteria and cause superior bactericidal efficacy as compared to the free doxycycline counterpart. Our results suggest that the reported liposome system holds a substantial potential for gastric drug delivery; it remains inactive (stable) in the stomach lumen but actively interacts with bacteria once it reaches the mucus layer of the stomach where the bacteria may reside.
authors.affiliation: Department of NanoEngineering, ‡Moores Cancer Center, University of California, San Diego , La Jolla, California 92093, United States.
authors.forename: Soracha
authors.initials: S
authors.lastname: Thamphiwatana
authors.forename: Victoria
authors.initials: V
authors.lastname: Fu
authors.forename: Jingying
authors.initials: J
authors.lastname: Zhu
authors.forename: Diannan
authors.initials: D
authors.lastname: Lu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry; D016480:Helicobacter pylori / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000138:chemical synthesis / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D010316:Particle Size; D013270:Stomach / Q000737:chemistry / Q000187:drug effects* / Q000382:microbiology; D013329:Structure-Activity Relationship; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D008081:Liposomes; D006046:Gold; D004318:Doxycycline