Application of Liposome as Drug Carrier
Liposomes are bilayer vesicles composed of phospholipids as the main material, and were first discovered by Bangham, a British scientist. Liposome’s structure is similar to biofilm, also known as artificial biofilm, and is widely used to study the structure and function of biofilm. Liposome used as a drug carrier began in the early 1970s. Due to the advantages of biocompatibility, biodegradability, non-toxicity and non-immunogenicity, liposomes have rapidly developed as new drug dosage forms. After more than 40 years of research, there are currently 12 liposomal preparations on the market. The drugs involved include adriamycin hydrochloride, amphotericin, muramyl-tripeptide, paclitaxel, gentamicin, and cytosine arabinoside, etc. In addition, various types of liposomes are under study, such as liposomes being heat-sensitive, magnetic-sensitive, pH-sensitive, anti-drug resistance, active targeting, multifunctional, and liposomes of various routes of administration such as injections, lungs, nasal cavity, transdermal, oral, etc. Liposome research is becoming more and more extensive and in-depth.
Liposome Type
Liposomes can be divided into three types according to their morphological size: ①Small unilamellar liposomes (SUV), unilamellar vesicles with the particle size of 20 ~ 80 nm; ②Large unilamellar liposomes, unilamellar vesicles with the particle size of 100 ~ 1000 nm; ③Multilamellar vesicle (MLV) with the particle size of 1 ~ 5 pm. The drugs are distributed in different parts of the liposome according to the solubility. The hydrophobic drugs are distributed in the lipid bilayer, and the water soluble drugs are encapsulated in the inner aqueous phase. The drugs in the outer aqueous phase can only be regarded as free drugs since they exist independently with liposomes. Some drugs, such as those nucleic acids with negative charges can be adsorbed on the surface of positively charged liposomes, and are also liposome preparations.
Development of Liposome Drugs
The distribution of the drug in the liposome is determined by the liposome, and the properties of the drug loaded in the liposome have changed greatly. Therefore, the pharmacokinetics, tissue distribution, toxicity and other behaviors of liposome drugs may change significantly. According to the existing production research and development results, the main reasons for restricting the clinical application of liposomes are the stability of liposomes, the applicability of scale-up production equipment, and the safety of liposome preparations. In August 2002, the FDA Center for Drug Evaluation and Research drafted Liposome Drug Products: Chemistry, Manufacturing, and Controls; Human Pharmacokinetics and Bioavailability; and Labeling Documentation, which provided detailed guidance for the application of liposome drugs, including the formulation composition, physical and chemical properties, production process control parameters, product quality control, human pharmacokinetics and biological degree, product usage and dosage. Whether the liposome preparation process conditions are reasonable ultimately determines whether it can be produced on a large scale. During the screening process of the prescription process, the screening indicators should be comprehensive. The liposome composition, the quality control of the excipients, and the quality control of the liposome preparation, including the encapsulation rate, leakage rate, particle size, stability (product’s stability and lipid materials’ stability) and other factors, should be comprehensively considered. And the key process conditions and steps should be verified to explain the rationality and reproducibility of the process. In addition, it is also necessary to give a clear explanation of the process equipment and demonstrate the feasibility of scale-up production in order to ensure product safety, effectiveness and quality control.
Liposomes have been proposed as drug carriers since the 1970s, and were once abandoned due to drug leakage and rapid elimination from the blood. After more than 20 years of research, in 1995, the first anti-cancer liposome preparation Doxil was approved by the FDA for marketing in the United States. After this, the international pharmaceutical community began extensive research on liposomes.