| Summary: | 碩士 === 高雄醫學大學 === 天然藥物研究所 === 100 === Artocarpus incisus (Thunb.) L. f. (Moraceae) is a kind of food and traditional medicine for curing and preventing diseases, such as diarrhea, stomachache, infection, and herpes. Our preliminary study had been demonstrated that the dichloromethane fraction of A. incisus heartwood (AD) had telling effect in anti-proliferative activity to human melanoma A375.S2 cell. However, the poor aqueous solubility of AD is the limiting factor to develop as an anticancer drug.
The aim of the present study was used cyclodextrin as carrier to resolve the solubility problem. In physicochemical characterization, particle size analysis (PSA) and transmission electron microscopy (TEM) were used to realize the changes of the particles size distribution and morphology. Solubility and encapsulation efficiency were detected by high performance liquid chromatography (HPLC). The differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) were used to analyze the changes of crystal structure. Fourier transform infrared spectroscopy (FT-IR) was used to figure out the intermolecular bonding of cyclodextrin and AD. Furthermore, the determination of anti- proliferation in A375.S2 cell was used to compare the anticancer activity between raw AD and the best formula. And transdermal absorption study was used the Franz diffusion cell to investigate the skin penetration of the best formula.
According to the results, the formula of 2-hydroxypropyl-β- cyclodextrin (HPBCD) was better than β-cyclodextrin (BCD). HPBCD and AD (the weight ratio, 8:1, HD81) had lowest particle size (125.73 ± 3.66 nm) and best solubility (261.19 ± 0.91 μg/mL) than other formulas, and the encapsulation efficiency was 75.07 ± 0.48%. In FT-IR spectra, HD81 showed that the OH stretch of AD at 3207 cm-1 was shifted to 3403 cm-1 and that indicated HPBCD formed hydrogen bond with AD. The results demonstrated that HD81 was the best formula for enhancing water solubility. Moreover, HD81 had better anti-melanoma activity than AD in water and similar to AD in DMSO. And the data also demonstrated that HD81 can be penetrated horny layer into epidermis (8.00 ± 1.19 μg/cm2、26.41 ± 3.90%) and dermis (3.67 ± 1.64 μg/cm2、11.98 ± 5.93%). Consequently, we suggest that HD81 may be an anti-melanoma drug in further investigation.
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