Preparation And Study On Triptolide Loaded In Lipid Nanoparticles For Transdermal Drug Delivery System

Aims: The objective of the present study was to prepare,evaluate and explore penetration mechanisms and transport properties of triptolide-loaded in nanoparticles(TPL-NPs),including nanostructured lipid carriers(TPL-NLC)and solid lipid nanopqrticles(TPL-SLN)for transdermal drug delivery.Methods: TPL-NPs were prepared with emulsification technique and central composite design-response surface methodology(CCD-RSM)was used to optimize the formulations.Skin-blood synchronous microdialysis system coupled with a high performance liquid chromatography-mass spectrometry(HPLC/MS)method was used for TPL-NPs pharmacokinetic analysis in rat skin and blood.Different platforms were applied to evaluate the skin multifaceted changes.Distribution process in skin and in Ha Ca T cells of nanoparticles was assayed by confocal laser scanning microscopy(CLSM)and fluorescence microscope with coumarin-6 as model drug.And ELISA assay was applied to verify the in vitro anti-inflammatory activity.Results: The optimized TPL-NLC and TPL-SLN possessed higher encapsulation efficiency,drug loading and cumulative penetration quality.In vivo skin pharmacokinetics demonstrated that the concentration of TPL-NLC and TPL-SLN in skin was higher than that in blood,and performed a sustained release profiles,and that reduce toxicity and srynergistic effect of TPL.TPL-NPs could disorder skin microstructure,alter thermodynamics,and extract corneum lipids and keratin.Nanoparticles could escape from lysosome and be observed in skin cells cytoplasm.And most nanoparticles firstly accumulate in hair follicle and distribute into the whole skin sample after 1 h treatment.However,TPL-NLC rather than TPL-SLN could significantly suppress expression of skin reaction factors.Conclusion: TPL-NLC and TPL-SLN was successfully constructed in the research.This study also clarified the enhanced penetration mechanisms and transport properties of nanocarriers,which provide a step for TPL-NPs used in transdermal drug delivery theoretically and practically.The results suggested that TPL-NLC and TPL-SLN are promising agents that could be developed for transdermal transporter.