Study On The Fabrication Of CZ48 Loaded Cerasomes And Its Freeze-drying Technology

Camptothecin has shown potent anti-tumor activity with poor stability and severe toxicity in vivo.Camptothecin-C20-propionate(CZ48),a camptothecin derivative,improves the structural stability and circumvents the side effects.Cerasomes,self-assembled from cerasome-forming lipids(CFLs)are liposomal nanohybrid.Comparing with liposomes,the silicate surfaces improve the morphological stability of cerasomes.In the present thesis,The physical and chemical properties of CZ48 were studied.CZ48 is a hydrophobic compound and showed optimal solubility of 45.77±0.34 mg/mL in chloroform.The solubilities of CZ48 in buffer at the different pH were poor.The oil/water partition coefficient of CZ48 is 0.82.CZ48 loaded liposomes,cerasomes and composite cerasomes(formed by CFLs and phospholipid)were prepared via thin-film hydration method with particle sizes of 155.73?249.97nm,encapsulation efficiency of 51.61?73.89%and drug loading capacity of 2.68?3.69%.As CFL content decreased in CZ48 loaded composite cerasomes,the accumulated in vitro drug release and Zeta potential increased along with the decrease of particle size,encapsulation efficiency and drug loading capacity.composite cerasomes(containing 30%?50%and 70%CFLs)had similar drug release pattern and reached a well sustained release.Compared with CZ48 loaded liposomes,CZ48 loaded cerasomes showed better morphological stability.In composite cerasomes,the morphological stability increased with the increase of CFL ratio.Treated with 30 fold of Triton X-100,liposomes were cracked or agglomerated,whereas cerasomes and composite cerasomes with the CFL contents higher than 50%were unaffected,indicating the cerasomes have well morphological stability.The Freeze-drying process for CZ48 loaded cerasomes were studied.Using CZ48 loaded composite cerasomes containing 70%CFL,mannitol as the cryoprotectants and the concentrations of CZ48 loaded composite cerasomes and mannitol at 4 mg/mL,the freeze-drying agent showed optimal shape and the accumulated release within 12h was over 95%comparing with fresh prepared CZ48 loaded composite cerasomes.