Preparation And Evaluation Of Honokiol-loaded Micelles

Honokiol(HNK)is a natural compound extracted from the roots of Magnoliaceae plants.It has a wide range of pharmacological effects,including antioxidant,anti-inflammatory,antibacterial and anti-tumor effects,and low toxicity.Studies showed that HNK can inhibit the growth of various tumor cells and has no toxic effect on normal cells.However,the application of HNK has been severely limited by its poor water solubility,easy oxidation,rapid metabolism in vivo and low bioavailability.As a drug delivery system,polymer micelles can not only improve the water solubility and bioavailability of drugs,but also improve the aggregation degree of drugs in the lesion site modified by target molecules.Moreover,polymer micelles could be prepared more easily than other drug carriers through self-assembly.In this paper,the F127-CS was prepared from pluronic F127 and Chitosan(CS)through multi-step reactions.Then F127-CS was modified with Biotin(BIO)to obtain F127-CS-BIO.The structure of F127-CS-BIO was characterized by ~1H-NMR and FT-IR,and its critical micelles concentration and hemolytic activity were investigated.HNK-loading micelles were prepared by dialysis method,and its X-ray diffraction,FT-IR,stability and releasing behavior in vitro were investigated.Mouse melanoma B16 cells were used as cell model to study the in vitro cell activity of HNK-loading micelles,including in vitro antitumor activity,trypan blue staining,morphological observation and cell uptake.It was found that the average encapsulation efficiency and drug loading of HNK-loading micelles were 75.97±1.70%,9.85±0.39%,respectively.The HNK solubility was increased to 1.013mg/m L,which was approximately 18 times of crude HNK.FT-IR and X-ray diffraction analysis showed that HNK exists in the micelles with amorphous state.The results of in vitro hemolysis study showed that the hemolysis of micelles was less than 5%in the experimental concentration range(78～5000μg/m L),which met the requirements of injection administration.In vitro release studies showed that the release of HNK-loaded micelles has obvious slow-release properties.In vitro cytotoxicity and cell uptake experiments showed that BIO-modified HNK-loaded micelles have better cytotoxic activity on B16 cells,and its cell uptake is higher than that of HNK-loaded micelles unmodified BIO.It confirmed that HNK-loaded micelles modified by BIO have good targeting properties to tumor cells,thus improving anti-tumor activity of HNK.