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Emergence of nano herbal drugs!

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Despite their tremendous therapeutic potential, poor bioavailability, metabolic instability and aqueous insolubility impeding herbal drug’s commercialization potential as main stream medicine. The development of nanoherbal composites and nano drug delivery systems are indispensable to overcome various constraints of traditional herbal dosage forms like poor bioavailability, in vivo stability, aqueous insolubility, intestinal absorption and unspecific site of action. Nanotisation enhances the surface area of the herbal drugs, which allows quicker dissolution in the blood with enhanced retention time and also helps in crossing blood-brain barrier. According to the BCC Research report, the market value of the worldwide nanomedicine industry was estimated as US$96.9 billion by the year 2016.

Since ancient days, plant derived natural products have been used for the treatment of human diseases. The basis of modern medicine still being inspired from traditional medicine and therapies. Ayurveda is one of the ancient form of medicinal system practiced in India. It uses various active medicinal   ingredients derived from plant based extracts and calcined minerals (bhasmas) either stand alone or combination.  The herbal formulations available in the market primarily based on the ancient texts heavily relies on belief, lacks standardization and more over most of these products are not tested with modern pharmacopic methodology. Therefore, their working mechanisms are relatively ambiguous and selectivity to the particular diseases are not well defined. The application of the modern nanoscience methods to the traditional system of medicine enhances the potential of herbal drugs for treating chronic diseases such as cancer and various other ailments.

“Nanoparticles can penetrate any site of the body, even neurons. It means we can deliver drugs straight to cancer cells so the healthy cells are not affected”

Nanotized or micronized active herbal ingredients are increasingly become indispensable in enhancing the efficacy of neutraceuticals and over the counter drugs. Chemotherapy is an important mode of treatment at any stage of cancer. Chemotherapy drugs lacks selectivity, which in discriminatively kills both healthy cells and cancer cells, which leads to serious side effects. Radiation therapy is the most commonly used technique used for solid tumor treatment. Given the serious side effects of standard anti-cancer drugs, there is a growing demand for herbal drugs to mitigate the drug toxicity and improve the therapeutic index. According to Cancer Research UK (CRUK) herbal medicine is one of the most commonly used complementary and alternative therapies by people with cancer. Some studies have shown that as many as 6 out of every 10 people with cancer (60%) use non-standardized herbal remedies alongside conventional cancer treatments, which indicates the mass popularity of ayurvedic medicine. Recent research findings demonstrates that there is an evidence that herbal remedies may help to prevent or relieve the symptoms of cancer or treatment side effects.

An overview of our efforts to develop a nanoherbal drug for anti-cancer

With the goal of standardizing and enhancing efficacy of herbal drug actives in proprietary ayurvedic medicine, Oncocur India identifies and develops novel nano herbal drug targets and adjuvant drugs for the treatment of cancers. Adjuvant therapy with Oncocur’s nano herbal formulation BRECAN showed significant improvements in the tumor reduction as compared with chemotherapy alone. Adjuvant nanoherbal drug helps in improvement of immune cell count and reduced side effects as compared with chemotherapy alone. Our nano herbal medicine, BRECAN is also associated with a reduction in the risk of anaemia and a reduction in the risk of neutropenia. Nanoparticles can penetrate any site of the body, even neurons. It means we can deliver drugs straight to cancer cells so the healthy cells are not affected. Company is collaborating with Professor Andrew Wheatley in the Department of Chemistry from the University of Cambridge on developing novel drug delivery systems to deliver herbal actives selectively at the tumor.

Nanoscience has already redefined the pharmaceutical industry and currently herbal drugs and ayurvedic medicine industry is going through the nanotech revolution. Nano-preparations of herbal extracts and phytochemicals are an emerging platform for the efficient delivery of anti-cancer drugs such as Curcumin, Andrographolide and Taxol. To exploit various anti-cancer properties of the potential anti-cancer drug candidates such as Curcumin, Andrographolide, Kedros foetidissima various nanoformulation strategies being applied such as liposomes, micelles, nanoemulsions, cyclodextrin complexes, solid lipid nanoparticle conjugates.

Curcumin, a polyphenol compound extracted from turmeric, has been now widely used in proprietary ayurvedic medicines in India, USA and Europe. Curcumin has great potential for the development of a therapeutic  and it is known for range of therapeutic functions such as anti-inflammation, anti-cancer, inflammatory bowel, wound healing, Alzheimers, rheumatoid arthritis, and diabetes. Curcumin has been tested for 120 for various clinical trials in the last decade.  Despite its therapeutic potential, unfortunately Curcumin appears to lack the properties required for a good drug candidate (chemical stability, high water solubility, interacts with many different proteins and so works differently from many drugs).  Therefore, chemically modified or functionalised forms of nanocurcumin will be more effective at reaching tissues and generating adequate pharmacology data to meet modern drug standards.

“The application of the modern nanoscience methods to the traditional system of medicine enriches the potential of herbal drugs for treating chronic diseases such as cancer and various other ailments”

Like Curcumin, another phytochemical isolate under intense investigation for its anti-cancer property is Andrographolide. Andrographolide, a diterpenoid lactone, which is one of the major bioactive components of the Acanthaceae family plant called Andrographis paniculata. It has been studied for its beneficial properties such as anti-inflammatory, analgesics, antihuman immunodeficiency virus effects, immunoregulation, neuroprotective, choleretic cardiovascular, anti-hyperglycemic and antitumor and has been widely used in clinic for the treatment of fever, inflammation, and other infectious diseases.

Despite its impressive biological activities, the major constraints of Andrographolide are poor oral bioavailability, short plasma life and inappropriate tissue localization making it difficult to prepare formulations for clinical use. It is unstable in extremes of gastrointestinal alkaline and acidic conditions and has a very short biological half-life. Therefore, it is essential to design and develop hybrid derivatives of Andrographolide in a manner to act as first line anti-cancer chemotherapeutic agents. It is envisaged that development of a suitable nanodelivery systems will help in improvement of pharmacokinetics of this investigational drug.

Another potential armor in the arsenal to fight against cancer is an extract of medicinal plant called Kedrostis foetidissima, which has been identified and developed by Pune based Oncocur India. The company has been successful in animal trials in demonstrating the therapeutic efficacy for breast, colon and ovarian cancers better than standard drug paclitaxel. The tubor extracts of K. foetidissima clearly reveal the anti-cancer properties and it is evident that the findings of the present study can provide a basic concept for synthesizing a new drug. The company is focusing on developing nanoparticle formulation to bring down the cost, improve the efficacy and pharmaco kinetic parameters to meet regulatory standards.

Till date most of the herbal extracts are primarily used in ayurvedic industry, majority of them are small scale enterprises uses traditional mortar and pestle based methodologies. In order to penetrate into the global mainstream market, widen its acceptance across the continents, the industry has to adopt WHO GMP standards and new venture investments into research and development. Currently the research has been conducted by largely govt institutes. The industry requires impetus from the government in the form of commissioning new research programs and grants for revision of knowledge in order to establish working principle. Despite its huge market potential, R&D investment in the private sector is dismal partly due to the weak IP enforcement in India and opaque IP guidelines on herbal extracts.

Why is a nanotech based drug most effective as cancer cure?

Cancer is a complex and evolving disease. As of today, there is no specific and selective drug for cancer. Blood vessels in tumors are “leaky” because they have gaps from 200-2000 nm, which allow nanoparticles to escape into the tumor. Nanometer sized particles below 500nm  can promote tumor selectivity and aid in delivering low-solubility drugs. Nanoparticles can be targeted passively or actively. Passive targeting exploits the difference between tumor blood vessels and normal blood vessels. In the current cancer care, chemotherapy, radiation therapy, hypothermia has been used  in-combination more often than standalone. Researchers have been studying on new phytochemical and their synthetic analogues which can fight against cancer and counter the side effects caused by the current chemo and radition methods.

Safer cancer medicine will have profound impact on the patients and their caregivers. One can debate the standalone therapeutic efficacy of herbal drugs however their adjuvant synergistic effects are indispensable for current cancer care and much research is needed to develop as mainstream drugs using nanotechnology approaches. Given the unmet need of cancer patients by current standard of care, there is a great opportunity waiting to be untapped for these phytochemicals to develop them as drugs. With the support of more venture funds, we can develop scientifically validated formulations to meet the regulatory guidelines using nanotechnology approaches.

Owing to their relatively lower drug toxicity and greater efficacy nano-herbal medicines are in high demand especially as anti-cancer combination drugs. It is the high time to apply modern methodologies to revise and standardize the ancient knowledge to tackle emerging global healthcare challenges such as multi-drug resistance antibiotics and cancers.

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