Factors Influencing the Properties of Rifampicin Liposome and Applications for Dry Powder Inhaler

RIF encapsulated liposome vesicles were prepared by chloroform film method followed by freeze drying technique to obtain a dry powder for aerosol delivery. The freeze drying conditions were designed according to the DSC results of the liposome suspension. Three sugars (mannitol, lactose and trehalose) were used as a cryoprotectant of liposome dry powder. NR 8383 cell line was used to determine immunological activation and toxicity of liposome products when LPS from E.coli was used as a positive control. High cholesterol content in the formulation created higher rigid bilayer membrane of liposome vesicle than the lower cholesterol content formulation thus provided a better physical stability. The lipid content had influenced on degree of encapsulation, higher lipid content in formulation produced higher % encapsulation. Mannitol was a suitable sugar for this dry powder aerosol when it provided a free flowing powder with an MMAD less than 5 mum (3.35 mum). In addition, RIF in liposome dry powder form showed better chemical stability than in suspension form after they were kept for 6 weeks both at 4degC and room temperature. The reconstituted liposome powder in PBS pH 7.4 gave the encapsulation about 22%. The products did not cause toxicity to the cell line and did not activate immune responses since the cell produced very low level of toxic cytokines (IL-lbeta and TNF-alpha) when compared to LPS. This indicates that the particles are able to reach alveoli without stimulation of immunological response and safe to alveolar macrophage.