Design, engineering and biological performance of responsive lipid vesicles for enhanced drug delivery by mild hyperthermia

摘要: The design of a delivery system that specifically delivers anticancer drug to the tumour site avoiding normal tissues damage has always been challenge. In this thesis we describe engineering and biological performance novel temperature-sensitive liposomes (TSL) have both substantial in vivo stability an efficient content-release by mild hyperthermia (HT). First, explain development lipid-peptide hybrids (Lp-Peptide) anchoring leucine zipper peptide within liposomal lipid bilayer. We characterized studying its physicochemical properties interaction with Then examined potential retain trigger release drug, doxorubicin, vitro at physiological temperatures after exposure HT. addition, blood kinetics, other accumulation were explored when studied vivo. Our data suggested Lp-Peptide can increase immediate long-term tumour. Therefore, their therapeutic activity comparing two different heating protocols mimic intravascular interstitial release. last chapter opportunities increasing specificity TSL designing anti-MUC-1 targeted vesicles based on traditional (TTSL) specific uptake into cancer cells. was evaluated cellular binding, efficacy. Taking step further, biodistribution also examined. Different applied explore effect HT TTSL summary, our studies demonstrate critical factors consider clinically relevant importance matching protocol pharmacokinetic parameters maximise benefits.