| .Oxaliplatin (trans-L-diaminocyclohexane oxalatoplatinum, OHP), a novel cisplatin derivative, is a third-generation platinum analogue with proven anti-tumor activity against many tumor cell lines, and has been approved for standard first-and second-line treatment of metastatic or advanced-stage colorectal cancer. However, its clinical efficiency is limited by the dose-limiting and side effects such as toxicity to the kidneys and peripheral nerve system. Substantial efforts have been dedicated to solve these problems. One of the most intriguing strategies to overcome these drawbacks is to encapsulate L-OHP in a targetable drug delivery system, which can selectively deliver the drug with a relatively high concentration to tumors. Liposomes are the archetypal, simplest form of a targetable drug delivery system, and have been researched many years for using in pharmaceuticals. Liposome is a closed vesicle comprising phospholipids, which are derived from biological material, as a main component. It exhibits a number of advantages in terms of amphiphilic character, biocompatibility, ease of surface modification rendering, cause no or very little antigenic, pyrogenic, allergic and toxic reactions. Furthermore, some reports indicate that encapsulation of drugs in liposome has a particle size of100to200nm and enables to control their stability in blood and biodistribution, resulting in improved delivery efficiency of their payloads to cancer. So, we prepared Oxaliplatin liposome modified with folic acid-conjugated polyethylene glycol (FA-OHP-liposome) in order to improve therapeutic effect and reduce side effects. Following contents are included in this paper..1. Firstly, the HPLC method was established to determine the Oxaliplatin concentration. The OHP-liposome was prepared, and the quality was evaluated. To optimize the prescription and preparation of oxaliplatin liposome, many preparation methods of liposome were used, such as ultrasonic method, thin-film hydration method, reverse phase evaporation vesicles method, and freeze-thawing method. The best prescription and preparation of oxaliplatin liposome was reverse phase evaporation vesicles method. The best experimental factors:lecithin:cholesterol was6:1; the concentration of the lecithin was100mg· mL-1; the ratio of drug:phospholipids is1:50; the dosage of the poloxamer F68was2mg· mL-1. The preparation of oxaliplatin large unilamellar vesicles were processed with a high-pressure homogenizer at300bar, in three minutes. The liposome had an envelope efficiency of oxaliplatin of49.27%and homogeneous shape with the particle size at85nm.2. The FA-PEG4000-MS was added as the components during the preparation of liposome. FA-OHP-LP and free drug were separated by tangential flow filtration. The FA-OHP-LP had an encapsulation efficiency of oxaliplatin of92.15%and homogeneous shape with the particle size at102nm, and The concentration of OHP615.38μg· mL-which meet requirements established by China Pharmacopeia2010..3. The surface morphology, average diameter and size distribution, zeta potential, release in vitro, stabilities for FA-OHP-LP were studied by various methods. The results show that FA-OHP-LP were mainly circular and uniform and had no adhesion; the average mean diameter was106nm; zeta potential was (36.5±5) mV; the encapsulation efficiency was higher than90%; the system could maintain stability after three months. Release of FA-OHP-LP in vitro could be described by first order dynamic model and could be described by the equation:ln(1-Q)=-0.1653t-0.4628(R2=0.9768). |
PDF Full Text Request