Research On Innovative Drug Delivery System Based On Nanohybrid Liposomal Cerasome

Malignant tumor is one of the most refractory disease risks for human health, chemotherapy drugs is absolutely necessarily therapeutic method. Most commonly used anticancer drugs are not specifically toxic to tumor cells and are toxic to all tissues they contact so they create undesirable side effects as a result of their interactions with normal tissues. These toxic side effects hinder their development and applications. Liposomes have received increasing attention as possible carriers for diagnostic or therapeutic agents. Especially, liposomes have been used to formulate a variety of hydrophilic and hydrophobic, poorly soluble drugs. Thus, liposomes are unstable to the circulation environment and/or its content will leak the antineoplastic agent prematurely before reaching the tumor site. The insufficient stability of liposomes may limit their applications. To overcome these problems, scientists have developed long-circulating liposomes—pegylated liposomes. The pegylated liposomes appeared to reduce some of the toxic effects caused by the release of their contents, but, unfortunately, new toxic effects appeared because of the presence of the polyethylene glycol. For example, the liposomal preparations containing pegylated phospholipids have lead to skin toxicity generally known as "Hand-Foot syndrome," which results in skin eruptions/ulcers on the palms of the hands and soles of the feet. So many scientists consider: preparing more stable and tumor-targing liposomes will be the development direction of liposome technique in the future.To overcome these problems, recently, a novel super-stable and freestanding hybrid liposomal cerasome (partially ceramic- or silica-coated liposome) was fabricated using self-assembly and a sol–gel strategy to overcome general problems associated with current liposome technology. First, we successfully synthesized the cerasome-forming lipid. Then we prepared cerasomes and studied the optimal preparation technics. Cerasome is a bioinspired colloidal particle having an inner aqueous compartment like the liposomal membrane but its surface is covered with the inorganic silica framework. In addition, the nontoxic silica surface protects the inner lipid bilayer and is amenable for bioconjugation with silane-coupler chemistry. This biomimetic material is remarkably high stability towards surfactant solubilization, and acidic treatment, compared with conventional liposomes. Therefore, cerasome vesicles are of major importance due to their potential applications for the encapsulation of a variety of guest species including hydrophilic, hydrophobic and amphiphilic molecules.The current study demonstrates for the first time that hybrid liposomal cerasomes can be used as a new promising drug delivery system. A lipophilic anticancer drug paclitaxel (PTX) and a hydrophilic anticancer drug doxorubicin (DOX) were used as test drugs and loaded in cerasmes to prepare PTX-loaded cerasomes (PLCs) and DOX-loaded cerasomes (DLCs). We studied the optimal preparation technics to obtain PLCs and DLCs with uniformity paticle size of 150nm and non-aggregated vesicles. The two cerasome pharmaceuticals are with high morphological stability and storage stability with good biocompatability. In vitro release of drugs experiments indicated cerasomes can release the drug for a sustained period of time. Later, the "mixed" cerasomes were fabricated from mixtures of the cerasome-forming lipid and phospholipids. The―mixed‖cerasomes were characterized various methods. These results strongly indicated that cerasome-forming lipid and DSPC were both incorporated in one vesicle, not macroscopically phase-separated to form separate vesicles of each lipid component alone. It also provided us an ability to modulate the release rates of encapsulated drugs by altering the ratios of the cerasome-forming lipid and phospholipids. We prepared magnetic cerasomes composed of doxorubicin (DOX) and superparamagnetic iron oxide (Fe₃O₄). To study the cell uptake, the NBD-labeled magnetic fluorescence cerasomes (MFCs) were prepared and was characterized by confocal laser scanning microscopy and flow cytometer. These results indicated that magnetic DOX-loaded cerasomes (MDCs) are a promising candidate for treating cancer and monitoring the progress of the targeted cancer therapy with stability, sustained release and targeted ability.This paper successfully prepared four super stable cerasome pharmaceutics, PLCs, DLCs, PTX loaded mixed cerasomes and MDCs. Cerasome is the high stable lipid bilayer, so that this artificial cell membrane has beautiful applications prospects for the biology medicine field. Cerasome vesicles as drug carrier have their potential applications for cancer therapy and will bring large economic benefits.