A self-targeting liposomal drug carrier with water as a pH-responsive functionality

Zwitterions possess both cationic and anionic groups, allowing full reversal in zeta potential from below to above zero in response to a change in environmental conditions. Zwitterions for use in self-targeting platforms are usually hydrophilic and have a negative charge under physiological conditions (pH 7.4) providing low adsorption of proteins and assisting blood circulation. Besides, the unique advantage of liposomes delivering cargo based on fusion of the liposomal membrane with a target, made me chose for liposomal nanocarriers, despite the challenge to design a biocompatible pH-responsive funtionality of the liposomal carrier. Based on these choices, this thesis is aimed towards the development of new liposomes as a drug-carrier, in a first instance functionalised in order to allow biofilm targeting from the blood circulation, penetration and accumulation over the entire thickness of an infectious biofilm, associated with deep killing in the biofilm. However, the thesis also extends to tumor self-targeting.
In chapter 2, a zwitterionic liposome with water as a pH-responsive functionality for targeting of acidic infection sites is described. In chapter 3, zwitterionic liposomes with water as a pH-responsive functionality are prepared, loaded with bromelain as a biofilm dispersant and the antibiotic ciprofloxacin incorporated in the lipid membrane of the liposomes. In chapter 4, liposomes with water as a pH-responsive functionality were applied loaded with antibiotics and cancer-chemotherapeutics in a new infected tumor model. In the General Discussion of this thesis, the merits of these new, self-targeting liposomal drug-carriers are discussed and suggestion for further use are presented.