INTRODUCTION:

Since ancient time, herbal remedies and natural products are being used to cure the diseases. Disparate to widely used allopathic system, the herbal remedies have thousands of constituents that all work concurrently against the diseases. Phototherapeutics need a scientific approach to deliver the components in a sustained manner to increase patient compliance and avoid repeated administration. This can be achieved by designing novel drug delivery systems (NDDSs) for herbal constituents.

NDDSs not only reduce the repeated administration to overcome noncompliance, but also help to increase the therapeutic value by reducing toxicity and increasing the bioavailability. Inclusion of the herbal extracts into novel formulation systems have certain added reward, such as their bulk dosing and less absorption can be overcome which is the prime crisis being faced, tempting the attention of major pharmaceutical corporations. Nanotechnology is a field of applied science and technology which aims to develop devices and dosage forms in the range of 1 to 100 nm. The applications of nanotechnology for treatment, diagnosis, monitoring, and control of biological systems have recently been referred to as nanomedicine. The nanocarriers have been made of safe materials, including synthetic biodegradable polymers, lipids, and polysaccharides. The activity of herbal medicines depends on overall function of a variety of active components, as all the constituents provide synergistic action and thus enhance the therapeutic value. Each active constituent plays a vital role and they are all correlated to each other. However, most of the herbal origin drugs possess insoluble character leading to lower bioavailability and increased systemic clearance requiring repeated administration or higher dose, which makes the drug as a poor candidate for therapeutic use. In phytoformulation research, developing nano dosage has large number of reward for herbal drugs, including enhancement of solubility and bioavailability, protection from toxicity, enrichment of pharmacological activity, enhancement of stability, improving tissue macrophages distribution, sustained delivery, protection from physical and chemical degradation, etc. Thus, the nano sized drug delivery systems of herbal drugs have a potential outlook for enhancing the activity and overcoming problems associated with plant medicines. Hence, integration of the nanocarriers as a NDDS in the traditional medicine system is essential to conflict more chronic diseases like asthma, diabetes, cancer, and others.

The origin of nanotechnology is often attributated to a concept advanced by Richard P. Fenyanman .The word nano derived from the Greek noun “nano” meaning “dwarf”.

History:

Nanotechnology is a new science but ayurveda has been using it long before the term ‘nano’ was formed. Some of the formulations of ‘bhasma’ have nano particles in them. For many researchers it is still a great surprise that the 5000year old Indian system of medicine had some knowledge of nano science and technology, which modern science has just started exploring in the 21st century. While the concept of reduction in particle size of metals is prevailing since Charak Samhita, the oldest classical text in ayurveda. The bhasmas used in Ayurveda for treatment of various diseases for the past several centuries is the oldest form of nanotechnology. The nano particles are 1 crore times smaller than a hair and due to its small size; the basic characteristics also get changed. Due to change in electrical, thermal, magnetic, optical, chemical and biological characteristics, the particles can be used for various products.

Need for novel drug delivery system for herbal remedies:

Many constituents of the herbal drugs will be smashed in the highly acidic pH of the stomach before reaching to the blood and other constituents might be metabolized by the liver. Resulting, the optimum quantity of the herbal drugs may not reach the blood. If the drug does not reach in the optimum amount to the infected region at “minimum effective level,” then there will be no therapeutic effect of the drug. Nanocarriers applying to herbal remedies will carry optimum amount of the drug to their site of action bypassing all the barriers such as acidic pH of stomach, liver metabolism and increase the prolonged circulation of the drug into the blood due to their small size.

Herbal remedies were selected as feasible drug candidate for delivery through a nano delivery system because of the following properties:

1. Effective chloroform, petrol, acetone, and methanolic extracts are available which may not be suitable for delivery as such.

2. These are the bulk drugs so dose reduction is intended.

3. Currently marketed formulations lack target specificity for various chronic diseases.

4. Some other side effects are associated with currently marketed formulations.

5. Patient noncompliance due to large doses and less effectiveness with the available formulations.

Compensation of Nanosized delivery system:

1. They appear to be able to deliver high concentrations of drugs to disease sites because of their unique size and high loading capacities.

2. Deliver the drug in the small particle size that enhances the entire surface area of the drugs allocating quicker dissolution in the blood.

3. The concentration seems to persist at the sites for the longer periods.

4. Shows enhanced permeation through the barriers because of the small size and retention due to poor lymphatic drainage such in tumor.

5. Exhibits passive targeting to the disease site of action without the addition of any particular ligand moiety.

6. Decrease in the side effects.

7. Decrease in the dose of the drug formulation.

Nanopharmaceutics:

In pharmaceutical all the procedures that work at nanoscale level is called Nanopharmaceutics.

Nanopharmaceutics present revolutionary opportunities to fight against diseases. The choice of nanopharmaceutical material is done by its characteristics such as biodegradability, bioavaibility, encapsulation efficiency and functionality.

Classification of nanopharmaceuticles:

Nanopharmaceuticles are classified as follows:

v Solid lipid nanoparticals

v Magnetic nanoparticals

v Metal and inorganic nanoparticals

v Quantum dots

v Polymeric micelles

v Phospholipids micelles

v Colloidal nano-liposome’s

v Dendrimers

Fig 1- Nano particles

Techniques:

The techniques commonly used for the formulation are:

1. High-pressure homogenization method:

In this method, the lipid is pushed with high pressure (100 to 2000 bar) through a very high shear stress, which results in disruption of particles down to the submicrometer or nanometer range. High-pressure homogenization method is a very reliable and powerful technique for the large scale production of nanostructured lipid carriers, lipid drug conjugate, SLNs, and parenteral emulsions.

2. Complex coacervation method:

This is a spontaneous phase separation process of two liquid phases in colloidal systems, which results by the interaction of two oppositely charged polyelectrolyte upon mixing in an aqueous solution.

3. Coprecipitation method:

This method is a modification of the complex coacervation method for the preparation of nanoscale coreshell particles. This method has been reported to provide good dispersion stability to poorly water soluble drugs.

4. Saltingout method:

This method is based on the phenomenon that the solubility of a nonelectrolyte in water is decreased upon addition of an electrolyte.

5. Nanoprecipitation method or solvent displacement method:

This method is based on interfacial deposition of a polymer after displacement of a semipolar solvent miscible with water from a lipophilic solution, thereby resulting in a decrease in the interfacial tension between the two phases, which increases the surface area with a subsequent formation of small droplets of organic solvent even without any mechanical stirring.

6 .Solvent emulsification–diffusion method:

The method involves preparation of an o/w emulsion using oil phase containing polymer and oil in an organic solvent, which is emulsified with the aqueous phase, containing stabilizer, in high shear mixer, followed by addition of water to induce the diffusion of organic solvent, thus resulting in formation of nanoparticles.

7. Supercritical fluid methods:

This method can be used to prepare submicrometersized and nanosized formulations. A supercritical fluid (SCFs) can either be a liquid or gas and used above its thermodynamic critical point of temperature and pressure. The most commonly used SCFs are carbon dioxide and water.

8. Selfassembly:

methodsSelfassembly is the physical process wherein preexisting disordered components, atoms, or molecules organize themselves into regulated nanoscale structures by physical or chemical reactions without any contribution from any external source.

Bhasma as a nanomedicine:

Metals are used as medicines in Ayurveda since from samhita period in the fine powder from named as ‘Ayaskriti’ latter with the development of ‘Marana’ technique (7 th cent AD) the metals and minerals are converted into very very fine and absorbable, therapeutically most effective and least or nontoxic form of medicines known as ‘Bhasma’.Bhasma are defined as powder form of a substance obtained by calcinations.

The Bhasma particles when analyzed microscopically through SEM and TEM fall under the range of nanoparticals of contempory science-ray diffraction, TEM and particle size analysis revealed that size of particles of Muktashukti Bhasma,swarna Bhasma, Abhrak Bhasma ,Tamra Bhasma and Louha Bhasma are in nanometer dimension.

Summary of patents for herbal nanoparticles:

1) Curcumin Nanoparticles

2) Carotenoids Nanoparticles

3) Silymarin Nanoparticles

4) Vinca alkaloids Nanoparticles

5) Panax ginseng Liquidmixture

6) Salvia miltiorrhiza extract Nanoparticles

7) Gymnema sylvestre extract Nanoemulsion

8) Withania somnifera Liquid mixture

9) Silybum marianum Tabletsor capsules

10) Curcuma longa Nanoparticles

11) Andrographis paniculata, Azadirachta indica, Bacopa monnieri, Cinnamomum Zeylanicum, Cnidium officinale, Coccinia indica, Crataegus oxyacantha Curcuma longa, Gymnema sylvestre, Juglans regia, Momordica charantia Mucuna pruriens, Ocimum sanctum, Panax ginseng, Panax quinquefolium, Paullinia cupana, Pfaffia paniculata, Phyllanthus emblic, Phyllanthus niruri, Pinus Maritima, Polygonum cuspidatum, Scutellaria baicalensis, Silybum marianum Syzygium cumini, Tinospora cordifolia, Trigonella foenumgraecum and Withania somnifera Nanoemulsion, nanoencapsulation, nanodispersion or synergistic liquid mixture

12) Lemon juice, Lepidium sativum Nanoemulsion

13) Safflower extract, Zanthoxylum piperitum extract, Torilis japonica fruit extact, Green tea leaf extract, Pomegranate extract, Pine tree leaf extract, Red ginseng extract, Ginseng extract, Angelicae extract, Salvia miltiorrhiza extract, Safflower extract, Zanthoxylum piperitum extract, Torilis japonica fruit extact, Cnidium officinalis makino extract, Green tea leaf extract, Pomegranate extract, Pine tree leaf extract, Red ginseng extract, Ginseng extract, Angelicae extract, Truigonella foenum graecum (Fenugreek) Nanoparticles, Nanoparticles mixture, Nanosuspensions, nano emulsions

14) Lepidium sativum , Green tea extract, Pomegranate extract Nanoformulation

15) Arbutin Emulsified nanoparticle

16) Aloe vera, guggul, green tea Organic nanoparticles

17) Capsicum species, Cascara sagrada Mesospore microparticulate

18) Citrus and cinnamon Solid nanoparticle dispersion

19) Vitamin, herb Bioadhesive nanoparticulate

20) Herbs Nanoparticles

21) Swertia japonica Nanoparticles

22) Almond oil, coconut oil, corn oil, cottonseed oil, linseed oil, olive oil, soybean oil, peanut oil etc. Micellar nanoparticles

23) Moringa oleifera Bionanoparticles

24) Agar Bio nanoparticles

25) Solanum Nanoparticles

26) Eugenol Nanoparticles

27) Piper betle, Dolichos biflorus, Commiphora mukul, Boerhaavia diffusa, Tribulus terrestris and Zingiber officinale Nanoparticles

28) Picrorhiza kurroa Royle, Picrorhiza scrophularii flora Pennell and Neopicrorhiza scrophulariiflora Nanogel, nanoparticle

29) Capsaicin Nanoparticle,nanocapsules

30) Butea isoflavones Nanoparticle, nanoemulsion

31) Chloroquine Nanoparticles

32) Fenugreek extract Nanoparticle

33) Picrorhiza kurroa Royle Nanoparticles

34) Picrorhiza kurroa Royle, Picrorhiza scrophulariiflora, Pennell Picrorhiza kurroa Royle, and Neopicrorhiza scrophulariiflora Nanoparticles

35) Triterpene Glycoside Nanoparticles

36) Melissa officinalis, Calendula officinalis, Camellia seninsis, Aspalatus linearis Nanoparticles

37) Oregano leaf extract Nanoparticles

38) Scutellaria baicalensis, Glycyrrhiza uralensis, Ziziphus jujuba, and Paeonia lactiflora Nanoparticles

39) Black cohosh Nanoparticle

40) Cucumis sativus Nanoparticle

Toxicity issues:

Although nanopharmaceuticals may promise endless opportunities in the field of drug delivery for the diagnosis and treatment of various diseases, their safety should not be ignored.

The change in the physicochemical and structural properties of engineered nanosized materials with a decrease in size could be responsible for a number of material interactions that could lead to toxicological effects. At present, scientists must accept that it is still very early in the toxicological evaluation for nanomaterials and nanomedicines, and there are only few data on the safety and toxicity.

Future prospective:

All over the world, the research has been going on herbal remedies and natural products. The development of herbal remedies in the drug delivery system in a number of institutes is being carried out at basic and clinical trial levels. The only requirement is to develop the better systems for the proper delivery of such drugs at the sites and in the whole body in the doses which will not compromise with the existing treatment. Something that would not only give relieves from side effects like toxicity and hypersensitive reactions but also will increase the patient's strength

From inside is very much desirable. In the future, the concept of herbal nanoparticles for cancer drug delivery may also fascinate some potential research groups and potentially create attention grabbing results. Hence, using “herbal remedy” in the nanocarriers will increase its potential for the treatment of various chronic diseases and health benefits. Many successful examples with experienced evidences are present among us in the direction of nano research. Herbal remedies are also prosperous resources of advantageous compounds holding antioxidants and constituents that can be made use in purposeful foods. This type of collaborative research among the traditional “Herbal remedies” and newer approaches of modern drug delivery system, i.e., “Nanotechnology” has established the attractive therapies to the pharmaceutical in near future that will enhance health of people. It is anticipated that the effectual and valuable relevance of the natural products and herbal remedies being applied with the nanocarrier will enhance the significance of existing drug delivery systems.

CONCLUSION:

The ‘Nano’ is the recently used word but in Ayurveda nanoparticals of drugs obtained from natural sources are being used as an effective medicine. It is the need of the moment for Ayurveda to conduct the researches to extend the use of our nano medicines in various aspects like detection and diagnosis of the dieses to make them more effective in serving the society.

The combination of nanotechnology with traditional herbal medicine may provide a very useful tool in designing future herbal medicines with improved bioavaibility profile and less toxicity.

REFERENCES:

1) Jadhav NR, Powar T, Shinde S, Nadaf S. Herbal nanoparticles: A patent review Asian J Pharm 2014 ;8 : 1: 58-69

2) Sahu AN Nanotechnology in herbal medicines and cosmetics Int. J. Res. Ayurveda Pharma. 2013;4:3:472-474

3) Kulkarni S S. Bhasma and Nano Medicine Int. Res. J. Pharm. 2013;4:4:10-16

4) Ansari SH, Islam F, and Sameem minfluence of nanotechnology on herbal drugs: A Review J Adv Pharm Technol Res. 2012; 3:3:142–146.

5) Yadav D, Suri S, Choudhary AA, Sikender M, Hemant, Beg NM, et al. Novel approach: Herbal remedies and natural products in pharmaceutical science as nano drug delivery systems. Int J Pharm Tech. 2011;3:3092–116.

6) Kulkarni G Nanotechnology – Current Need of Ayurved Medical Care for Parents2015:1-3

7) Chaudhary A. Ayurvedic Medicines: Myths and Realities. Journal of Ayurveda and Holistic Medicine 2014 ;2 :2:1-4

8) Padmavathi M. Drug Delivery System in Nano greens International Journal of Herbal Medicine 2013; 1 :3: 56-60

9) Yadav M, Bhatia VJ, Doshi G, Shastri K. Novel Techniques in Herbal Drug Delivery Systems Int. J. Pharm. Sci. Rev. Res 2014;28:2: 83-89

10) Gomes A, Ghosh S, Sengupta J, Datta P, Gomes. A herbonanoceuticals: A New Step Towards Herbal Therapeutics. Med Aromat Plants 2014;3:3:1-9

11) Verma H, Baboo SP, Singh H. Herbal Drug Delivery System: A Modern Era Prospective International Journal of Current Pharmaceutical Review and Research, 4:3: 88-101

12) Patwardhan B, Vaidya AD, Chorghade M. Ayurveda and natural products drug discovery. Curr Sci 2004; 86:789.

13) Sahni JK, Baboota S, Ali J. Promising Role of Nanopharmaceuticals in Drug Delivery. Pharma Times 2011; 43:16-8.

14) Kannissery P. Novel Drug Delivery System of Eugenol against Inflammation and Periodontal Infection. Indian Etd Repository @ inflibnet 2013:1-181

15) A Decadal vision document Towards Ayurvedic Biology 2006 Indian Academy of Sciences

Received on 14.10.2015 Accepted on 12.12.2015

Asian J. Pharm. Res. 5(4): October- December, 2015; Page 203-207

DOI: 10.5958/2231-5691.2015.00031.3