Advance and Prospect of Nanoscale Chinese Medicine
Department of Dermatology, No. 1 Affiliated Hospital of Inner Mongolia Medical College, Inner Mongolia010050, P. R. China
*Corresponding authors. E-mail: email@example.com
Over the past few years, nanoscale Chinese medicine has emerged as a new exciting field in which theoretical and experimental studies of structure and function of nanoscale Chinese drugs have become a focus, and the importance of quality standardization of nanoscale medicament of Chinese traditional medicine as specific drugs to the fundamental development in traditional Chinese drugs has begun to be recognized. In particular, Chinese medicine dispersion, surface potentials, envelopment ratio, loading drug amounts, in vivo metabolism dynamics, bio-distribution, drug-releasing in vitro, etc., have become a new interdisciplinary frontier in life science and Chinese traditional medicine. There is an increasing need for a more systematic study of the basic issues involved in traditional Chinese medicine and a more active participation of researchers in the application area of nanoscale traditional Chinese drugs. Some advances have been and are being made in nanoscale Chinese herbs, mineral medicine including mongolia drugs such as cinnabar, with enormous prospect in clinical disease therapy. Here we review some of the main advances in this field over the past few years, explore the application prospects, and discuss the concepts, issues, approaches, and challenges, with the aim of stimulating a broader interest in developing nanoscale Chinese medicine.
Keywords: Chinese medicine; Nanotechnology; Toxicity; Metabolism; Therapy
Citation: R. Wu. Advance and Prospect of Nanoscale Chinese Medicine. Nano Biomed Eng. 2010, 2(3), 193-200.
Chinese medicine is the general name of traditional drugs in China, which comes from natural plants, ani- mals and minerals, includes three kinds of formats such as Chinese herbs, drink-slips and nostrum . It is well known that traditional Chinese medicines are composed of complicated compositions, which decides the pharmaceutical complexity of traditional Chinese medicines. How to realize the standardization of tradition- al Chinese medicine is a great technological challenge. Nanotechnology brings a new chance to solve current problems in development of traditional Chinese medicine [2,3]. The concept of nanoscale Chinese medicine was firstly proposed by prof. Bihui Xu in Huazhong Science and Technology university, and has become a new topic in recent years. Nanoscale traditional Chinese medicine is defined as the effective components with less than 100nm in diameter, effective locations, primary drugs and compound pharmaceutics that are fabricated by nanotechnology. When the traditional Chinese medicine components reach less than 100 nm in diameter, these components are easily separated by using chemical means, qualitatively analyzed by physi- cal tools, and quantitatively analyzed by physical chemical methods, which is helpful to realize the tech- nological standardization of traditional Chinese medicine [4,5]. Absorption, distribution, metabolism and elimination of drugs in life organism is one complicated course, drug effective function is not only dependent on chem- ical structure components, and also closely associated with drug pharmaceutic types and physical status. To change the physical stages of Chinese medicine pharmaceutics is also an effective pathway to develop new drugs. Nanotechnology can be used to change the phys- ical status of Chinese medicine. When the drug particles reach nanoscale, nanoscale drugs exhibit some novel properties due to quantum effects and surface effects, which will enhance the drug activity and bio- logical availability as well as targeting, more important, which will be helpful to decrease the toxicity and side- effects of Chinese drugs, and realize the international standardization of Chinese medicine quality evaluation [6,7]. Although many fundamental problems remain un- clear, great advances have been made in the development of traditional Chinese medicine with biological and nanoscale character. In the following we review some of the main progresses made over the past decade or so in the preparation of nanoscale Chinese medicine, evaluation of nanoscale Chinese medicine effects, drug delivery systems, explore the application prospects, and discuss the concepts, issues, approaches, and challenges, with the aim of stimulating a broader interest in developing nanoscale traditional Chinese medicine.
2. Advance of Nanoscale Traditional Chinese Medicine
In recent years, nanoscale Chinese medicine has made some progress in these fields such as preparation of nanoscale Chinese medicine, evaluation of nanos- cale Chinese medicine effects and drug delivery systems.
2.1 preparation of nanoscale Chinese medicine
Traditional Chinese medicine mainly includes plant drugs such as herbs, and mineral drugs such as cinnabar, etc. Herb drugs are often crushed into nanoscale pieces by ultrasonic devices, and disintegrator under low temperature, and then furtherly were isolated out effective components. Mineral drugs such as cinnabar, etc. often are fabricated into nanoscale drugs by using chaser mill and burst method [1,8]. However, during the period of preparing nanoscale Chinese medicines, how to keep the bioactivity of Chinese drugs is still a great challenge.
2.2 Evaluation of nanoscale Chinese medicine bio-effects
Biological effects of nanoscale Chinese medicine is evaluated from four levels such as molecular level, cell level, animal level and human body level. At first, nanoscale Chinese medicines are analyzed their compo- nents and structures. Their bioactive components were isolated and identified. Then, culture different cells and incubate with different dose of nanoscale Chinese medicines, observe a series of cell reactions with the aim of evaluating nanoscale Chinese medicine’ cytotoxicity, biological function. Thirdly, establish animal models with different diseases, and feed nanoscale Chinese medicine and observe animal reactions, especially ob- serve the effects of nanoscale Chinese medicine on nerve tissues, important organs such as heart, liver, spleen, lung and kidney, etc. After these evaluations fully show that prepared nanoscale Chinese medicines are no or low toxicity, then those Chinese medicines are used for clinical patients. Clinical patients’ therapeutic effects will demonstrate the bioactivity of prepared Chinese medicines. In recent years, some studies fully show that nanoscale Chinese medicine can markedly enhance the bioavailability of Chinese medicine, therapeutic targeting, especially enhance the primary function, simultaneously increase the novel efficacy [9,10]. For example, Mengxiang Li, etc processed traditional Chinese medicine such as asparagus into nano- particles, and measured the mouse mitochondrial SOD activity, and liver tissue GSH-PX activity, their results showed that nano-scale asparagus exhibits higher anti- oxidant bioactivity than those prepared by the ultra- sonic extraction.
2.3 Pharmaceutical dosage forms of nanoscale Chinese drugs
The nanoscale Chinese medicines are different from traditional primary Chinese medicines, whose bioactiv- ities and bioavailability may be markedly enhanced, therefore, nanoscale Chinese medicine dosages for disease therapy should be lower than that dosage of primary Chinese medicines used. Due to particle size down to nanoscale, vein injection pathway, oral path- way and skin stick pathway should own better efficacy, the concrete pathway should be selected according to patient needs [11,12].
2.4 Nanoscale Chinese medicines delivery system
Nanscale Chinese medicine particles are less than 100 nm in diameter. In recent years, some drug deli- very systems are successfully fabricated. For example, solid lipid nanoparticle, liposome, nanostructured lipid carriers, and nanoemulsion, etc. have been successfully prepared, and exploringly used for nanoscale Chinese medicine delivery, and each delivery system has differ- ent advantages and shortcomings [13-17]. How to use fully their advantages is also a great challenge.
2.5 Standardization of quality of nanoscale Chinese medicine pharmaceutics
Quality standard of nanoscale Chinese medicines mainly are evaluated from the following nine aspects. No.1 step is morphology observation and particle size distribution. High resolution transmission electron microscopy and scanning electron microscopy are often used to observe the morphological changes of nanoscale Chinese medicines, MALVERN ZETAZIZER 2000 instrument often is used to measure the size distribution of Chinese medicine particles. Particles with more than 5 µm in diameter are often captured by lung capillary vessels, particles with less than 150 nm in diameter target marrow, too small nanoparticles can be swallowed by reticuloendothelial system, particles between 150nm and 200nm in diameter can target body circulation, particles with more than 250 nm in diameter can target spleen, and bigger particles is easier cleaned by kidney. No.2 step is to measure zeta potential of nanoparticles, with the aim to predict the stability of nanoparticle system. No. 3 step is to measure en- velopment ratio and the amount of drug loaded. No.4step to measure the in vitro release drug, no.5 step is to measure leakage ratio, No.6 step is to investigate in vivo drug metabolism dynamics, and bio-distribution. No.7 step is to do drug effect test, No.8 step is to measure leftover of organic solvent. No.9 is other spe- cific evaluation for nanoscale Chinese medicine [18- 24].
2.6 Advance of mineral Mongolia medicine Cinnabar
As a typical traditional old Chinese medicine, Cinnabar has been widely used in clinical therapy for al- most 2000 years in China. Cinnabar can inhibit central neural system excitability and play the role of sedative and hypnotic effect in vivo, while can kill skin bacteria and parasites in vitro. The main composition of cinnabar is HgS, which accounts for almost 96%, the other components include also contain MgS, Bi, Fe, Si, Ba, Ca, Cu, Mn, Sb, As, etc. Due to cinnabar includes mer- cury element, therefore, cinnabar is considered as the toxic substance, and is suggested to carefully apply for clinical therapy. However, in Chinese Pharmacopoeia of 2000, there are more than 45 kinds of medicines contain cinnabar and take up of 10% in the whole components [1,25,26]. So far, how to remove the toxic compositions or decrease the toxic degree of Cinnabar is still a great challenge. Nanotechnology is used to treat Cinnabar, and bring a potential new chance to develop cinnabar, and it is possible that nanotechnology makes Chinese traditional medicine enter into for- eign countries market.
2.6.1 Pharmacological properties of cinnabar
In Chinese Pharmacopoeia, the amount of cinnabar is defined that HgS should be more than 98% in final products. Recent research shows that cinnabar is abso- lutely toxic in vivo, because under those conditions of anaerobic, pH=7, T=37℃, and free sulfur, HgS can react with methyl materials and generate into methylational HgS, while Human Intestinal tissues has a similar environment, and absorbing cinnabar will increase the risk of poisoning. HgS in blood can conjunction with sulfur-group of hemoglobin by penetrating through the erythrocyte cell membrane, and then distribute into various body organs by mean of blood circu- lation, for example, kidney has the maximal concentration of Cinnabar, and followed by liver, heart, digestive system, brain and reproductive system. The animal ex- periments also show that absorption half-life period of cinnabar is 0.2 h, and the peak of HgS in blood is 11h, and half-life period of Hg in vivo is about from 65 to 75 days. Thus, it proves that cinnabar in human body is slow absorption and metabolism, and can accumulate in human body and produce the poisoning. When the amount of Hg in human body reach 100mg, human body will suffer from sensory difficulty, central nerve poisoning and Circulatory failure, and will be dead [27- 31].
2.6.2 Toxicity of cinnabar
Regarding the toxicity of cinnabar, some studies show that the toxicity of cinnabar mainly comes from Hg’s toxicity. After the patient eats cinnabar for a long time, gathered mercury in human body can cause the dysfunction of Liver and kidney, and finally result in patient’s death [31,32]. Some reports show that cinnabar can inhibit central nerve system excitability to some extent. Those mice in the control group is not affected, but the mice in the test group injected with Amphetamine exhibits clear antagonistic function and play significant role in the promotion of hypnotic chloral hydrate and fight against the role of pentylenetetrazol induced convulsions, but do not exhibit the effects on the pentobarbital sleep time and strychnine convulsions. Cinnabar does not exhibit significant acute toxicity to mice. After the rats were feed with cinnabar for three weeks, the liver and kidney exhibit some pathological changes, but these lesions can be restored in two weeks after stopping feeding with cinnabar. Some other reports show that, no matter where cin- nabar is originated from, what kinds of processing methods, cinnabar include still some insoluble and free mercury, which is over 300 times more than the stan- dards of our drinking water. In fact, any Chinese medi- cine containing cinnabar exist insoluble mercury. After mice were feed with cinnabar for the first day, the amount of mercury in the organs and blood was signif- icantly higher than that in the control group. The cin- nabar may decrease ferti