Study On Imiquimod-Loaded Lipid Nanoparticles

To exploit the new drug delivery system for imquimod, the composition and preparation technology of imiquimod-loaded nanostructured lipid carriers(IMQD-NLC) were investigated and the in vitro skin penetration and the mRNA expressions of TNF-α,IL-1βand IL-6 in the skin of BALB/C mouse in vivo of imiquimod incorporated in cream, nanostructured lipid carriers compared. A novel suitable topical drug delivery system for imiquimod, which can improve the local efect of imiquimod,increase the content of drug in the skin, decrease the negative effect and improve the treament for topical diseases, is expected to be achieved.According to the physical and chemical properties of imquimod, IMQD-DA-GMS-NLC was produced by high pressure homogenization using decanoic acid (DA) and glycerol monostearate (GMS) as natural biodegradable materials. single factor method was adopted to optimize the preparation parameters of IMQD-DA-GMS-NLC. The optimization parameters of the preparation of IMQD-DA-GMS-NLC: The mass ratio of DA/ GMS and S-40 / Span-20 were 1:3 and 1:1 respectively; The high pressure was 60MPa and the cycle times was 10. The mean diameter of optimized NLC was about 133nm and polydispersity index (PI) was about 0.348 respectively. The entrapment capacity was 94.68%. It confirmed us a burst release following by a sustaining release at pH1 and a sustaining release at pH5.8 in vitro forIMQD-DA-GMS-NLC.Additionally, another IMQD-OA-GMS-NLC was prepared using oleic acid (OA) and GMS as natural biodegradable materials.The influence of surfactant, high pressure homogenization parameter and capacity loading on the preparation of IMQD-OA-GMS-NLC were explored. The optimization parameters of the preparation of IMQD-NLC with the content 1 mg·ml^-1: The mass ratio of OA / GMS and S-40 / Span-20 were 2:3 and 1:1 respectively; The high pressure was 60MPa and the cycle times was 12. The mean diameter of optimized NLC was about 181 nm and polydispersity index (PI) was about 0.476 respectively. The entrapment capacity was 88.3%.Transdermal diffusion test equipment was used to examine and compare the in vitro transdermal diffusion of IMQD-DA-GMS-NLC,IMQD-OA-GMS-NLC and IMQD-CREAM.. The permeation rate of imquimod in IMQD-DA-GMS-NLC,IMQD-OA-GMS-NLC and IMQD-CREAM. was 7.54,13.88 and 7.84μg·cm^-2·h^-1 respectively, and the contents of imquimod in skin was IMQD-OA-GMS-NLC >IMQD-DA-GMS-NLC> IMQD-CREAM. In the skin of BALB/C mouse, the expression levels of TNF-α, IL-1βand IL-6 mRNA were statistically higher than the contralateral ear of the mouse.