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

Abstract

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.