1. Nanotechnology: A Challenge in Traditional Medicine
Dr. B. B. Barik
Professor, Department of Pharmaceutics,
College of Pharmacy, Jazan University
Kingdom of Saudi Arabia

2. Traditional Medicines include?
Diversity of health practices, approaches, knowledge, and beliefs incorporating plant, animal, and/or mineral-based medicines; spiritual therapies; manual techniques; and exercises, applied singly or in combination maintain well-being, as well as to treat, diagnose, or prevent illness
…..WHO

3. Categories of Traditional Medicine (TM)
Main Popular System of TM
Traditional Chinese Medicine
Indian Ayurveda Medicine
Arabic Unani Medicine
Homeopathy

4. MAJOR TRADITIONAL MEDICAL SYSTEMS
Ayurveda - widely practiced in India, Pakistan, Sri Lanka, Nepal, Tibet, Burma and other countries.
Traditional Chinese Medicine (China and used throughout Asia)
Unani Tibb or Greco-Arabian Medicine-being practiced in India, Pakistan, Bangladesh, the Middle East and a number of other countries.
Yoga - practiced for a long time all over India, Tibet, China and a few other countries and now spread to the Western countries.
Homoeopathy - widely practiced all over the world.
Tibetan and related systems of medicine.

5. AYURVEDA & TCM
Ayurveda is considered to be the most ancient of all medical disciplines.
In Ayurvedic medicine, the patient is viewed as unique, and ‘normality’ as what is appropriate for that particular person.
This is in contrast to Western medicine, where populations are generalized and ‘normal’ means what is applicable to the majority.
Chinese medicine is philosophically based, and as an holistic therapy the concept of balance and harmony is supremely important.
Philosophically, Ayurveda has similarities with traditional Chinese medicine (TCM).

6. TRADITIONAL MEDICINE Comprises of therapies employing
plant based products.
- Include herbs, herbal extracts, herbal preparations and finished herbal products, that contain as active ingredients, part of plants, or other plant materials, or combinations.
Well established and widely acknowledged to be safe and effective and may be accepted by national authorities.
Potent and effective as they were thousand years ago.
Alleviate wide range of diseases
Hence, call for development of delivery system for their attributes and principles.

7. Other opportunities for Traditional Medicine to address challenges in modern healthcare
Due to advances in medical science life spans are increasing and leading to a new set of health challenges around age related diseases, including cancer, cardiovascular disease, diabetes, etc.
Many drugs for treatment and prevention of chronic diseases
require long-term use - toxicity may aggregate over time.
Development of drug resistance and compensatory mechanisms is often an issue upon treatment.
Traditional medicine utilizes a systems biological approach to
target multiple mechanisms of disease treatment and prevention,
rather than focusing on treatment with single chemical medicines.
To overcome these different challenges, a traditional approach can be explored.

8. Mutations, Enzyme levels, Hormones and other Biological processes
Physical Factors:
Cold, Heat, Pressure, Radiations, Atmospheric composition, Rhythms
Mental Stress
Social
Economical
Chemical
Water Pollutants, Metal Pollutants, Pesticides, Preservatives, Additives,
Nutrition.
Mutations, Enzyme levels, Hormones and other Biological processes
Free Radicals
NEWER SYNDROMES/ LIFE STYLE DISORDERS

9. CONTD… NEED FOR HERBAL DRUG DEVELOPMENT
Many factors resulting from modern scientific technological advances disturbing universal laws of nature lead to increased prevalence of diabetes, cancer, hypertension, cardiac disorders etc. needs long term safe and effective therapies besides improvement in quality of life .
The changing concepts of health and disease and the understanding of the life process have demonstrated that the cure of an ailment is no more the sole possibility of a chemical drug or the knife of a surgeon.

10. NEED FOR HERBAL DRUG DEVELOPMENT - WHY?
Morbidity and Mortality due to drug reaction
Changing of environmental conditions causing many disorders.
Changing life style leads to increased incidence of life style diseases.
Aging and growing global population require an evolution in drug development.
- Herbal drugs are inexpensive in long term use
- Natural/eco-friendly
- No adverse effects in general
- Easily available

11. HERBAL MEDICINES – GLOBAL SCENARIO Populations using TM worldwide
Populations in developing countries using traditional medicine for primary health care
Ethiopia
Benin
India
Rwanda
Tanzania
Uganda
Populations in developed countries who have used complementary and alternative medicine at least once
Canada
Australia
France
USA
Germany

12. Novel Drug Delivery Systems (NDDS).…?
Goals:
Provide a therapeutic amount of drug to targeted
site of the body.
Maintain desire therapeutic efficacy of drug.
Minimize the levels of side effects.

13. Administration of high dose due HURDLES IN DRUG DELIVERY
Water insolubility
Administration of high dose due
to poor absorption
Nonspecific delivery
Poor bioavailability
Toxicity due
to chronic
exposure
Lack of drug
release
profile
HURDLES IN DRUG DELIVERY

14. NANOTECHNOLOGY: NANOPARTICLES:
Nanotechnology is an interdisciplinary research field developed with an amalgamation of chemistry, engineering, biology, and medicine, and has various useful applications in NDDS, and development of novel treatments.
NANOPARTICLES:
Nanoparticles are the end products of a wide variety of physical, chemical and biological processes some of which are novel and radically different, others of which are quite commonplace.
Nanoparticles may be defined as submicron (<1µm) colloidal systems, generally, but not necessarily, made of polymers (biodegradable or not).

15. NANOSCALE DRUG DELIVERY VEHICLE

16. Liposomes Nanoparticles
GOALS:
Control the particle size, surface properties and release of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate and dose regimen.
Difference between Liposomes and Nanoparticles:
Liposomes
Nanoparticles
Protecting drugs from degradation.
Less targeting to site of action.
Reduction toxicity or side effects.
Low encapsulation efficacy.
Rapid leakage of water soluble drug in the presence of blood components and poor storage stability.
Increase the stability of drugs.
More targeting to site of action.
Increase the encapsulation efficacy.
Minimize the leakage of water soluble drug in the presence of blood components.

17. Advantages of Nanoparticles:
Particle size and surface characteristics of Nanoparticles can be easily manipulated to achieve both passive and active drug targeting.
They control and sustain release of the drug during the transportation and at the site of localization
Subsequent clearance of the drug so as to achieve increase in drug therapeutic efficacy and reduction in side effects.
Drug Loading is relatively high and drugs can be incorporated into the systems without chemical reaction.
Site-specific targeting can be achieved by attaching targeting ligands to surface of particles.
The system can be used for various routes of administration including oral, nasal, parenteral, intra-ocular etc.,

18. Applications of novel drug delivery system for herbal formulations
Great advances have been made on development of novel drugdelivery systems (NDDS) for plant actives and extracts. 
Novel herbalformulations like polymeric nanoparticles,  nanocapsules, liposomes, phytosomes,nanoemulsions, microsphere, have been reported using bioactive and plant extracts. 
Novel formulations are reported to have remarkable advantages  over conventional formulations of plant actives and extracts which include enhancement of solubility, bioavailability, protection from toxicity, enhancement of pharmacological activity, enhancement of stability, improved tissue macrophages distribution, sustained delivery, and protection from physical and chemical degradation.

19. The Challenges which are commonly considered in nanotechnology based herbal products
(a) Solubility enhancement of poorly aqueous soluble or hydrophobic drugs
(b) Better permeability through biomembranes
(c) Faster absorption and good bioavailability
(d) Modification of biodistribution and pharmacokinetics
(e) Drug targeting and crossing biological barrier to deliver active component to specific organ or tissue
(f) Slow or inhibition of drug metabolism
(g) Increased gastric residence
(h) Toxicity, etc.

20. Characteristics of nanoparticles that influence the successful delivery of herbal drugs
Size of the nanoparticles
Physico-chemical properties of extracts, e.g., aqueous solubility and stability
Surface properties, e.g., charges, shapes, porosity, permeability etc.
Degree of biodegradation
Biocompatibility and interaction
Toxicity
Drug loading in nanoparticles and encapsulation efficiency
Release profile of active component from the product, e.g., type of release (immediate release, controlled release or targeted release), order of release (zero order or first order release), and mechanism of release (dissolution, diffusion, matrix system etc.)
Antigenicity, etc.

21. OPPORTUNITY FOR NANOTECHNOLOGY BASED TRADITIONAL MEDICINES
Curcumin,
isolated from the rhizomes of Curcuma longa Linn. (Zingiberaceae) and
widely accepted as traditional medicine in Southeast Asia.
It is commonly used as spice and nutritional supplement,
Used as antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, anticancer activities and potentially acts against various malignant diseases, diabetes, allergies, arthritis and Alzheimer's disease etc.
Major problems associated with its use are its low solubility, bioavailability and stability. Curcumin is reported to be unstable in the gut, and little amounts of curcumin that pass through the GI tract are rapidly degraded.
Nanotechnology has been successfully utilized here and has proven to be very effective in solving these problems.

22. ---- Contd ---- In vitro therapeutic efficacy of nanoformulated
curcumin and free curcumin against a panel of
human pancreatic cancer cell lines showed comparable results.
Novel polymeric amphiphile conjugates with hydrophilic and hydrophobic segments showed minimal toxicity on HeLa cells.
Nanocrystal solid dispersion of curcumin, amorphous solid dispersion, and nanoemulsion exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin with significant improvement in pharmacokinetic behavior.

23. Taxol
It is a potent anticancer drug particularly for leukemias and solid tumors in the breast, ovary, brain, and lungs.
Taxol suffers from the fact that it is water insoluble.
Ethanol or Cremophor EL are generally used for solubilization which have side effects.
Polymeric NP drug delivery system for Paclitaxel improve therapeutic index and adverse effects of Cremophor avoided.
Nanoparticles strongly enhances the cytotoxic effect as compared to Taxol.

24. Paclitaxel was loaded in sterically-stabilized, biocompatible, and biodegradable phospholipid nanomicelles expresses >10-fold higher P-gp than its parental sensitive cell line, MCF-7 when compared with Paclitaxel resistance in human breast cancer cell line.
PLGA nanoparticles loaded with camptothecin (a cytotoxic alkaloid isolated from Camptotheca acuminate) and conjugated with antibodies against colorectal tumor cells. It was observed that the uptake of antibody-nanoparticles was increased in the cell compared to the nanoparticles without the antibody and increased cytotoxicity of camptothecin.

25. Ginkgo biloba
Ginseng
Ginko biloba
Sources: Grape seed, hawthorn, milk thistle, green tea, and ginseng
Active Component: Flavonoid and terpenoids
Drugs can be embedded or dissolved in nanoparticles and can also be adsorbed or coupled on the surface. Encapsulating drugs within NPs can improve the solubility and pharmacokinetics of drugs.
The leaf extract of Ginko biloba L. has been widely used for brain cell activation properties. The nano sized G. biloba extract is expected to activate the brain cell and work on the treatment of Alzheimer's dimentia (like loss of memory, thinking, language, judgement and behaviour) better than pure extract [30].

26. -- Contd. ---
The leaf extract of Ginko biloba L. has been widely used for brain cell activation properties. The nano sized G. biloba extract is expected to activate the brain cell and work on the treatment of Alzheimer's dimentia (like loss of memory, thinking, language, judgement and behaviour) better than pure extract.

27. Hypoglycemic effects
Syzygium jambolanum
Gymnema sylvestre
PLGA nanoencapsulated forms of Syzygium jambolanum and Gymnema sylvestre have been shown to have relatively more hypoglycemic effects than their unencapsulated extract. Nanoformulation of active phytoconstituents, gymnemic acids has shown to improve their physiological action, pharmacokinetic and pharmacodynamic behaviors compared with that of some marketed products.

28. Licorice
Glycyrrhizin and glycyrrhetinic acid are the main bioactive compounds of licorice
They are widely used in medicine for the treatment of many liver diseases.
Chitosan nanoparticles were prepared &modified with glycyrrhizin and confirmed that nanoencapsulated drugs were preferentially accumulated in the rat hepatocytes by a ligand receptor interaction.
It is also found that the cellular uptake of liposomes modified with glycyrrhetinic acid by rat hepatocytes was 3.3-fold higher than that of unmodified ones. 

29. The pharmacokinetic behavior and physicochemical factors related with delivery systems are considered to be primarily responsible for the improved targeting and therapeutic effectiveness; therefore, dealing with these factors during development of nano-herbal formulation can lead to more promising treatments for acute and chronic diseases. 
Therefore, the nanoformulation can overcome the disadvantages of poor aqueous solubility, physical instability, low drug absorption, lower bioavailability, slow pharmacological action, drug targeting, faster elimination, toxicity of many herbal drugs.

30. Conclusion
but…
Traditional Medicine will contribute to human health care in the 21st century.
There are many challenges to the safety and effective use of traditional medicine.
But there are huge scope for nanotechnology based traditional medicines.
It is long way to go...

31. References:
1. Debjit bhowmik, Chiranjib, R.Margret chandira B.Jayakar. Role of nanotechnology in novel drug delivery system. Journal of Pharmaceutical Science and Technology, Vol 1(1), 2009, 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– Sharma AT, Mitkare SS, Moon RS. Multicomponent herbal therapy: A review. Int J Pharm Sci Rev Res.2011;6:185–7. 4. Aggarwal, B.B.; Kumar, A.; Bharti, A.C. Anticancer potential of curcumin: Preclinical and clinical studies. Anticancer Res. 2003, 23, Bisht, S.; Feldmann, G.; Soni, S.; Ravi, R.; Karikar, C.; Maitra, A. Polymeric nanoparticleencapsulated curcumin ("nanocurcumin"): A novel strategy for human cancer therapy. J.Nanobiotechnol. 2007, 5, Gelderblom H, Verweij J, Nooter K, Sparreboom A. Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. Eur J Cancer. 2001;37(13):1590–1598. doi: /S (01)00171-X. 7. Rozzi, A.; Nardoni, C.; Corona, M.; Restuccia, M.R.; Falbo, T.; Lanzetta, G. Weekly regimen of Paclitaxel and carboplatin as first-line chemotherapy in elderly patients with stage IIIB-IV non small cell lung cancer (NSCLC): Results of a phase II study. J. Chemother. 2011, 22, Samadder A, Das S, Das J, Paul A, Khuda-Bukhsh AR. Ameliorative effects of Syzygium jambolanum extract and its poly (lactic-co-glycolic) acid nano-encapsulated form on arsenic-induced hyperglycemic stress: a multi-parametric evaluation. J Acupunct Meridian Stud 2012; 5: [PMID: DOI: /j.jams ].

32. Thank You