Zedoaria Em MTC
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Applications of Nanoparticles in HerbalMedicine: Zedoary Turmeric Oil andIts Active Compound -Elemene
Meiwan Chen,a Shengpeng Wang,a Miao Tan and Yitao Wang
State Key Laboratory of Quality Research in Chinese Medicine
Institute of Chinese Medical Sciences
University of Macau, Macau, China
Abstract: Zedoary turmeric oil and its main active ingredient -elemene are novel plant-derived anticancer agents with long-term clinical application history and low toxicity, whichhave been approved by the Chinese SFDA to treat different tumors including cancers of thebrain, ovary, prostate, breast, lungs, liver, colon, and other tissues. Unfortunately, theirhydrophobic properties, poor stabilities and low bioavailabilities seriously hamper theirapplications in clinic. Therefore, more attention should be paid to develop novel drugdelivery systems for zedoary turmeric oil and -elemene to enhance their overall quality.Recently, increased research has been carried out on a nanoparticle drug delivery system ofzedoary turmeric oil and -elemene to solve their poor aqueous solubilities and low bioa-vailabilities in vivo with much remarkable achievements springing up in the last decade. Thisreview presents the novel nanoparticle formulations of zedoary turmeric oil and -elemeneand introduces the possible future prospects of their further study.
Keywords: Nanoparticle Drug Delivery of Systems; Zedoary Turmeric Oil; -Elemene;Research Perspectives; Review.
Zedoary turmeric oil, which is extracted from Curcuma phaeocaulis Valeton, Curcumakwangsiensis S. G. Lee et C. F. Liang, and Curcuma wenyujin Y. H. Chen et C. Ling, hasbeen linked to protection against liver injury, as well as reported anticancer, anti-throm-botic, and anti-virus effects (You et al., 2006; Sun et al., 2009a). Elemene, curcumol,curdione, germacrone, and pinene are marked as the main biological active components inzedoary turmeric oil. Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane, Fig. 1) is
Correspondence to: Dr. Yitao Wang, Institute of Chinese Medical Sciences, University of Macau, Av. PadreTomas Pereira S.J., Taipa, Macau, China. E-mail: email@example.comThese authors contributed equally to this work.
The American Journal of Chinese Medicine, Vol. 39, No. 6, 10931102 2011 World Scientic Publishing Company
Institute for Advanced Research in Asian Science and MedicineDOI: 10.1142/S0192415X11009421
an antitumor drug used for different tumors, including glioblastoma (Yao et al., 2008). Theextract of elemene is a mixture of -, -, and -elemene, with -elemene as the maincomponent, accounting for 6072% of the three isoforms (Zhang et al., 2010b). Zedoaryturmeric oil and its active ingredient of -elemene have been shown potent activity for theblockade of cell cycle progression, inducing cell cycle G2/M, G0/G1 arrest, andenhancement of the cytotoxicity effect of cisplatin, decetaxel and taxanes in many cancercells (Sun et al., 2009b). However, the clinical application of zedoary turmeric oil and-elemene has been limited by their hydrophobic properties, poor stability and low bioa-vailability, etc. So far, injections, freeze-dried powder, aerosol, and other formulations ofzedoary turmeric oil and -elemene have been used in the treatment of cervical and livercancer owing to its capability to inhibit tumor proliferation, improve clinical symptoms andquality of life, prevent transfer recurrence, and enhance immune function. -elemeneinjections, a wide spectrum anticancer drug with the main ingredient of -elemene, havebeen manufactured by several pharmaceutical companies in China since 1995 (Peng et al.,2006). However, -elemene injections have been reported as having side effects in clinicalapplications (Wang et al., 2006).
With the ongoing development of nanotechnologies, the novel delivery system ofzedoary turmeric oil and -elemene has developed. The emergence of nanoscience, whichis the creation and utilization of materials and tools on the nanometer scale, has exerted adeep inuence on numerous industries and particularly the pharmaceutical industry(Kumar, 2010). Increasing novel nanoparticulate formulations, such as liposome, micro-emulsion and microcapsules of zedoary turmeric oil and -elemene have been focused and
Figure 1. Chemical structure of Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane).
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will present a good perspective in their clinical applications. The application of thesenanoparticle formulations will deliver new approaches for enhancement of their solubility,stability, bioavailability, and pharmacological activity, and the ability to avoid physical andchemical degradation (Ajazuddin and Saraf, 2010).
In this review, we give an overview of the research progression for nanoparticle drugdelivery systems of zedoary turmeric oil and -elemene including liposomes, micro-emulsion and microcapsules in recent years. It is expected that the research level willimprove and be a scientic foundation for further pharmaceutical studies on zedoaryturmeric oil and -elemene.
Liposome as a novel drug delivery system has been used to improve the therapeuticactivity and safety of drugs for many years. Compared to the conventional formulations,liposome possesses the advantages of high biocompatibility, ease of preparation,chemical versatility, and simple modulation of pharmacokinetic properties by changingthe chemical composition of the bilayer components (Terreno et al., 2008). Up tonow, various traditional Chinese medicines (TCM) have been made into liposomes,including ginsenosides, tetrandrine, PNS (Panax notoginseng saponins), taxol, and others(Li et al., 2009).
For the formulation study, zedoary turmeric oil liposomes were prepared by a freezedrying method with a tertiary butyl alcohol-water cosolvent system and a single factortest (Yang et al., 2008). These liposomes were spherical with a mean diameter(457:3 7:8 nm), entrapment efciency (92:2 3:4%), the potential (23.6 mV), and48 h accumulative release (94.1%). In order to reduce its irritation, prolong its circulationand improve its efcacy, -elemene liposomes, such as PVP-coated liposomes (Zhanget al., 2006) and long-circulating liposomes (Liu and Li, 2010), were reported in recentyears. A number of studies have been published recently on the preparation methods,content determination, and pharmacokinetic proles of -elemene liposomes. Amongthese preparation methods, thin lm hydration (TFH), reverse-phase evaporation(REV) and REV plus high-pressure extrusion are the most common techniques. Acomparison of these three methods showed that the diameter of -elemene liposomeprepared by REV plus high pressure extrusion was smaller and more uniform, and theloading and the envelopment rate was higher than that using the traditional method(Huang et al., 2006).
For quality control of the zedoary turmeric oil and -elemene liposomes, high per-formance liquid chromatography (HPLC) has been developed to determine -elemene insterically stabilized liposome (Qi and Liang, 2008). The ultraltration-GC method isanother simple, accurate, sensitive, and applicable means to assay the content of zedoaryturmeric oil and -elemene liposomes (Xie et al., 2009). Cheng et al. (2010) determinedthe contents of curcumol and zedoary turmeric oil (ZTO) in liposomes containingZTO by a HPLC analysis and a spectrophotometric analysis to evaluate their quality.The entrapment efciency of ZTO was greater than of curcumol, but the yield efciency
APPLICATIONS OF NANOPARTICLES IN HERBAL MEDICINE 1095
of ZTO was less than that of curcumol in the liposomes containing ZTO. The percentageof curcumol in the ZTO would change in liposomes with different phospholipid pro-portions. The higher the phospholipid proportion, the higher percentage of curcumol inthe ZTO.
In addition, in vivo studies of -elemene liposomes showed that its pharmacokineticproles changed signicantly compared to the conventional forms. To investigate the tissuedistribution of -elemene liposomes in rats, the HPLC method was established to determinethe drug concentration in plasma and tissue (Song et al., 2007). Compared to the controlgroup treated with elemene injections, -elemene liposomes were distributed mainly in theliver, spleen, and kidney in rats after intravenous administration.
Solid Lipid Nanoparticles (SLN)
Solid lipid nanoparticles (SLN) are constructed from natural or synthetic lipid or lipoid,such as lecithin and triglycerides, which are solid at room temperature (Pardeike et al.,2009). The advantages of SLN include protecting labile compounds from chemicaldegradation, providing sustained release to improve the availability of the drug, andtargeting effect to improve the efciency of the drug (Zhu et al., 2009).
Film ultrasonic wave dissolving techniques are an important method of preparation forSLN. Using this method, the optimum formula was selected using an orthogonal designtest to prepare -elemene SLN: -elemene (20l), stearic acid (90mg), lecithin (90mg),Tween80 (2.5%, 5ml) and Poloxamer 188 (2.5%, 5ml) (Liu et al., 2007). Another methodis sonication and membrane extrusion (Wang et al., 2008). The result for the effects oftechnological factors on a mean particle size of -elemene SLN show that sonicationstrength, total length of the sonication period, and preparation temperature can inuencethe particle size.
SLN can be modied by folate receptors to achieve the targeted delivery of a drug totumor tissues. Wang et al. (2009) used the supersonic and membrane-extrusion methodto prepare a folate receptor-targeted SLN for -elemene. In vivo study has shown thatfolate receptor-targeted SLN circulates in the blood for a longer time and reach higherconcentration in many tissues compared to common SLN.