Results indicated that the optimal acyl chain length of the surfactant was between C(16) and C(18) with a saturated carbon chain and a PEG repeating unit ranging between 10 and 100 with a molecule weight above 600Da. In the panel of surfactants tested, Brij78 was optimal and could be incorporated into the liposomes by the thin film hydration or the postinsertion method with an optimal range of 1 to 8mol% . The authors continued with in vivo experiments in mice bearing mammary carcinoma cells EMT-6, investigating Gd3+DTPA (diethylene triamine pentaacetic acid) release with relaxometry. Inhibitors,research,lifescience,medical The authors observed a good correlation between relaxation enhancement
in the heated tumour and the inhibition of tumour growth at day 21 after treatment . Kono et al. investigated the effect of poly [2-ethoxy(ethoxyethyl)vinyl ether] chains (having a lower critical solution temperatures) and polyamidoamine G3 dendron-based lipids having Gd3+ chelate residues Inhibitors,research,lifescience,medical into PEGylated liposomes. These designed liposomes exhibited excellent ability to shorten the longitudinal proton relaxation time. When administered intravenously into tumour-bearing mice, accumulated Inhibitors,research,lifescience,medical liposomes in tumours increased with time, reaching a constant level 8h after administration by following T1-weighted MRI signal intensity in tumours. Liposome size affected the liposome accumulation efficiency in tumours: liposomes of about 100nm diameter were
accumulated more efficiently than those with about 50nm diameter. Tumour growth was strongly suppressed when liposomes loaded with doxorubicin were administered intravenously into tumour-bearing Inhibitors,research,lifescience,medical mice and the tumour was heated mildly at 44°C for 10min at 8h after administration . In our group we have investigated the potential of an MRI labelled phospholipid/lysolipid containing liposome to accumulate in tumours and release the drug under conditions of mild hyperthermia induced by FUS. We label the liposome Inhibitors,research,lifescience,medical nanoparticles with a lipid that consists of a DOTA [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid] headgroup (Figure 1) [44, 45]. Introducing the imaging lipid in the lipid bilayer provides a better and clearer monitoring of liposomal particle kinetics and a better knowledge of the time required for maximum nanoparticles accumulation in tumours (monitored medroxyprogesterone by MRI). Figure 1 Thermosensitive liposome for real-time monitoring of nanoparticle accumulation in tumours. Although most research studies have focused mainly in thermoresponsive liposomes and FUS activation of drug release, there is limited work on the use of polymers (thermoresponsive or not) and their application in FUS www.selleckchem.com/products/jq1.html triggered drug delivery. The effect of ultrasound on drug release from polymers was studied in 1989 by Kost et al. and indeed the authors found that ultrasound can increase the polymer degradation rate leading to 20 times higher release rate.