Molecular assemblies with stimuli-responsive properties are considered to be useful as drug delivery systems. For example, liposomes (lipid vesicles) with temperature-responsive and pH-responsive properties are used for site-specific drug delivery and intracellular drug delivery, respectively. These stimuli-responsive liposomes have been designed based on lipid phase transitions such as gel-to-liquid-crystalline transition and lamellar-to-hexagonal II transition. Recently, we developed a new type of stimuli-resistive vesicles using PAMAM dendron lipids which consisted of isobutyramide-terminated PAMAM dendron and two long alkyl tails. In their assemblies, densely packed isobutyramide groups on their surface generated temperature-responsive surfaces which change their hydration states depending on temperature [1]. Considering their possible application to drug delivery, in this study, we used oligoethylene glycols as temperature-sensitive terminal moieties and synthesized oligoethylene glycol-attached PAMAM dendron lipids for preparation of temperature-responsive molecular assemblies with biocompatible surface. These oligoethylene glycol-terminated PAMAM dendron lipid assemblies were stable at low temperature, but they became aggregated at a specific temperature when temperature was raised. The transition temperature of the assemblies was affected by dendron generation, oligoethylene glycol structure and alkyl chain structure. The transition temperature was also controlled by inclusion of PEG-cholesterol as an additional component of the vesicles. Interaction of these dendron lipid assemblies with cells was enhanced above the transition temperature, because their surface became highly hydrophobic above that temperature. Therefore, these assemblies might be useful as carriers that deliver drugs to the target site where local heating is applied. We further prepared vesicles from these oligoethylene glycol-attached dendron lipids and phosphatidic acid. These vesicles exhibited the transition depending on both temperature and pH. Because these vesicles were strongly destabilized only when trapped in weakly acidic environment such as endosome and mildly heated, they might have potential usefulness for temperature-controlled intracellular drug delivery to target tissues.1) K. Kono, et al., Angew. Chem. Int. Ed. 123, 6456-6460 (2011).

Design of PAMAM dendron-lipid assemblies with stimuli-responsive properties for drug delivery

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.