Liposomes As Drug Carrier Of Interferon-α

Interferons are principally produced and secreted by peripheral blood leukocytes, fibroblasts and epithelial cells in response to viral infection or other synthetic and biologic inducers that possess complex antiviral, antiproliferative and immunomodulating activities. They are in low bioavailability by routine administration, and usually cause a lot of adverse responses. Liposomes have been utilized as effective drug carriers, a vehicle for gene delivery and biomembrane modles. Liposomes have the potential to provide controlled release of the administered drug and increase the stability of labile drugs. Interferon-liposomes can alter the pharmacokinetics, tissue distribution and uptake of interferon in Comparison with free interferon. The purpose of this study was to investigate a novel and simple preparation technology of interferon- a liposomes with high entrapment efficiency and stability which is suitable for industrialization. The pharmacokinetic and the tissue distribution were studied.The uniform design coupled with computerized optimization was adopted to screen the formulation and preparation process. Pro-liposomes were prepared by powder bed grinding method and combined with interferon- a solutions to form interferon- a -liposomes. The particles were visualized by transmission electron microscopy. The size and distribution of the particles were determined by LS-230 particle size analyzer. Free interferon- a and interferon- a -liposomes were separated by gel filtration and ultrafiltration membrane filtration. Enzyme-linked immunosorbent assay were used for invitro and in vivo analyses. Chemical stability of liposomes was evaluated with oxidation rate of Sobey phosphatidylcholine. Residual ether was detected by gaschromatography. The effects of several factors on liposomes size, entrapment efficiency and stability were studied. The hemolytic test of interferon- a -liposomes was carried out in vitro and acute toxicity test of interferon- a -liposomes was studied in vivo. The tissue distribution in mice and pharmacokinetics in rats of interferon were studied after administration of interferon-a -liposomes or interferon- a solutions.The results demonstrated that the best formulation of interferon- a -liposomes is as follows. The protectant is sorbitol. Weight ratio for protectant and lipid is 5 '. 1. Weight ratio for Octadecytamin and lipid is 1 : 9. Weight ratio for Sobey phosphatidylcholine and cholestero is 9 '. 1. The particle size of interferon- a -liposomes is 80.8 + 36 nm and the entrapment efficiency of interferon- a -liposomes is 59.0 + 3.3 %. There were no effect of Lipid content and ratio of Sobey phosphatidylcholine and cholesterol on particle size of interferon- a -liposomes derived from pro-liposomes. But correlation between particle size of carrier material and particle size of liposomes were observed. The entrapment efficiency of liposomes was increased with increasing amount of lipid content or Octadecytamin. Residual ether of liposomes were lower than 23.8 u g/g, and the oxidation rate of Sobey phosphatidylcholine were only 0.607 ?0.034 %. Heat-aggregate test indicated that activation energy of liposomes was increased from 29.92 kJ / mol to 104.32 kJ / mol after frozen-thawed. When concentration of lactose achieved 1%, the entrapment efficiency of interferon- a -liposomes reached about 68.2+4.5%. There was little change in liposomes size and entrapment efficiency during half-a-year storage. The interferon- a -liposomes had no haemolysis and no toxicity after intravenous injection in the mice tail of different concentrations of interferon- a -liposomes or interferon- a solutions. The concentration-time curves of interferon- a -liposomes and interferon- a solution were fitted to a two-compartment model. The half-time of distribution phase (T 1/2 a ) of interferon- a -liposomes and interferon- a solution in the serum of mice were 66.15 +1.36min and 48.35 + 1.06min, respectively. The half-time of elimination phase (T\n$) of interferon- a -Hposomes and inter...