| FNC is a new synthetic kind nucleoside analogues of antiviral and antitumor. Through pharmacodynamic studies FNC has highly biological activity of pharmacological effects on against HIV (HIV) and hepatitis B virus (HB V).However its drug effection was infiuence in some extent because of its short half-life and short duration of drug concentration in liver, at the same time, bone marrow suppression,anemia and leucopenia can be cause. How to improve the FNC concentration in the liver, while extending the drug release time and reduce toxicity and adverse reactions is important to improve the pharmacodynamic efficacy.As a new drug delivery system liposome can passive targeting in the liver and spleen and make the drug more distributed in liver and spleen. At the same liposomes have multiple advantages, such as non-toxic, non-immunogenic, alter the distribution of the drug.Because of the deficiencies on FNC and the advantages on liposomes we prepared the FNC liposome to solve the problem of drug half-life, prolonged duration of action of the drug in the body, reduce the toxicity and adverse reactions, improve the bioavailability of drugs.Phospholipids and cholesterol were used main membrane,FNC as a model drug then prepared the FNC liposome and investigated the nature of its body outside. Specific studies include:1. The analysis methods of FNCAt first, HPLC analysis methoud of FNC was established for evaluating the quality of preparation.Then conducted the methodological study and established dialysis to separation FNC liposomes and free drug, HPLC method for determination of encapsulation efficiency.2. The preparation of FNC liposomeIn order to preparation of FNC liposomemes this study first examines the effects of several methods for the preparation of FNC liposomes, Determine the reverse-phase evaporation prepared FNC liposome, Then conducted the single factor for the formulation and preparation process,the results show that proportion of the drug and phospholipid, proportion of phospholipids and cholesterol, the aqueous phase volume were the influence factors. On this basis, encapsulation efficiency, drug loading and average particle size as an indicatoruse The use of composite design has been optimized for the prescription and processes, obtain the optimal prescription of FNC liposomes. FNC liposome encapsulation efficiency was 42.75%, an average particle size of104.7nm, drug loading was1.75%.3. The study on pharmacy properties of FNC liposomeFNC liposomes was prepared according to the optimal prescription and studied the nature of the pharmacy, The results showed that the appearance of uniform spherical,the average particle size was104.7±-44.46nm, Zeta potential was30.7±6.03mv. In vitro release results showed that in line with Riger-Peppas release model.4. The study of pharmacokinetics of FNC liposomeStudy the pharmacokinetics on the FNC liposomes and FNC solutions with rats. Plasma level of FNC content using HPLC-MS technology and analyze the results using DAS2.0pharmacokinetic processing software. The results showed that:FNC liposomes and FNC solutions are in line with the two-compartment model, The FNC encapsulated in liposomes can significantly improve its pharmacokinetic behavior, Compared with FNC solution, T1/2β extended to the3.354h8.459h, MRT extended to the4.467h6.327h; AUC increased nearly2-fold, CL of0.224L/h/Kg reduced to0.093L/h/Kg; FNC liposomes showed a prolonged duration of action has FNC sustained release effect, so FNC to maintain a high blood concentration of the drug in the body longer, increase the bioavailability of the drug, thereby increasing the efficacy of the FNC. |
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