Study On Preparation And Targeting Of Folate Modified Juglone Self Microemulsifying

Juglone,which is one kind of naphthoquinone,has significant anti-tumor effect.Previouds studies have shown that juglone can inhibit tumor cell proliferation strongly,which may be attributed to inhibiting the synthesis of deoxyribonucleotides,making mitochondrial vacuolar,and blocking potassium ion channels.Juglone is poorly water-soluble.Self-microemulsion is a novel drug delivery system developed in recent years.Self-microemulsion loaded with some quinone drugs can not only improve the stability,but also prolong the half-life of the drugs.Therefore,the therapeutic effect of the drugs can be significantly improved.At present,there have no study focus on preparing and evaluating the self-microemulsion of juglone.The objective of this study is to prepare a folic acid-modified self-microemulsion loaded with juglone and compare the targeting ability of juglone suspension,juglone self-microemulsion and folic acid-modified juglone self-microemulsion.Folic acid-modified self-microemulsion loaded with juglone can not only prolong the circulation time in vivo,but also enhance its targeting ability to cancer cells by means of the specific binding of folate receptor.The preparation of juglone self-microemulsion.The emulsifier,cosurfactant and oil phase of juglone self-microemulsion were screened by pseudo-ternary phase diagrams.The particle size and PDI were taken as indexes to optimize the formulation process through single-factor test.The optimal formulation process was described as follows.Thirty-five grams Cremophor EL,40 g Transcutol HP and 25 g ethyl oleate were mixed and stirred at 400 rpm at 37? for 3 min followed by adding 0.75 g juglone and then stirred to make juglone dissolve.The preparation of folic acid-modified juglone self-microemulsion.FA-PEG-CHEMS was prepared by sequential sampling method and confirmed by HNMR.The particle size and PDI were taken as indexes to study the consumption of FA-PEG-CHEMS by single-factor test.The optimal ratio of FA-PEG-CHEMS and emulsifier was 3:100.The folic acid-modified juglone self-microemulsion was prepared three times according to the optimal formation process.The average particle size was 41.06±0.39 nm and the average PDI was 0.263?0.005.The tumor-targeting of folic acid-modified juglone self-microemulsion.The SGC-7901 cell prolifation inhibition of juglone suspension,juglone self-microemulsion and folic acid-modified juglone self-microemulsion was evaluated by MTT with different incubation time(0.25h?1h?4h).Compared with juglone self-microemulsion,folic acid-modified juglone self-microemulsion exhibited better anti-cancer efficacy.The in vivo tissue distribution study of three jugone formations was evaluated by HPLC in S-180 tumor-bearing mice.The result indicated that folic acid-modified juglone self-microemulsion had much prominent tumor targeting ability.