Studies On The Amphotericin B Liposomes

In recent years, the incidence of systemic fungal infection and mortality rates were rising, amphotericin B is the classic drug for systemic fungal infection. However greater toxicity of injection amphotericin B, in particular, renal toxicity, long-term use will lead to kidney and circulatory system damage, greatly limiting its application, so people consider to make their lipid preparations. Liposomal amphotericin B first listed in the United Kingdom and Ireland in 1991, and it was the first liposome drug formulations.Because of poor solubility of amphotericin B, preparations of the amphotericin B lipid formulations"FengKesong" researched in Domestic, add a large number of surface-active substances deoxycholate solubilization. However, due to hemolytic toxicity of sodium desoxycholate, there are some security problems when the preparation was in use. Therefore, this study use different prescription and technology, referring to the relative literature and patents to study liposomal amphotericin B with a view to get higher bioavailability and toxicity smaller liposomes, to provide a more safe and effective preparations for clinical patients with systemic fungal infection.With the size, encapsulation efficiency of liposomes as the main evaluation index, liposome prescription was screened and single factor was inspected. And possible impact factors in the preparation were screened. When the best prescription and technology were determined, three batches of liposomes were produced to inspect the reproducibility, then to contrast all the changes of liposomes before and after freeze-dried. The stability of freeze-drying liposomes was inspected, including the impact of factors testing, accelerated stability test pilot and long-term stability. Analytical methods for phospholipids of liposomes were established, to examine the stability of the phospholipids of freeze-dried liposomes. Finally, pharmacokinetics trial with rats was conducted to study if the preparation of liposomes prepared has better nature than the listed liposomes.The liposomes with the particle diameter of 120 nm and encapsulation rate of more than 95 percent was prepared by film dispersion method .The form of liposomes was round and the particle size distribution was uniformity under light and electron microscopy. There was no significant change of the particle size and encapsulation efficiency of the liposomes after freeze-drying. Freeze-dried liposomes to the stability of, the results showed that the high temperatures, high humidity and strong light for the liposome has great influence on the stability with the morphological changes, drug leakage, encapsulation efficiency and content were significantly Lower. So it should be preserved at cold, dark, dry place. Acceleration and long-term tests showed that freeze-dried liposomes within six months are stable.There was a small amount of lysophosphatidic MSPC produced in high temperature and light conditions. In acceleration and long-term tests for six months, although the Phospholipids content was to lower, no lysophosphatidic was detected. Clearly, there was good stability of the liposome freeze-dried in the cold, dry, dark condition.Rats'pharmacokinetics of test results showed that the AUC of new preparation liposomal amphotericin B in rats increased four times than commercial preparations, "FengKesong". t_1/2αextend 1.5 times than the preparation of the market; t_1/2βextend 2.5 times than the original preparation. Therefore, this Pharmacokinetics results show that the preparation of liposome has a high bioavailability.The results of this study show that the preparation of liposomal amphotericin B has a good stability, in animal experiments also showed that the liposome has better t nature than the preparation of market. It has good development prospects and it is expected to provide patients with systemic fungal infection more safe and effective preparation.