NOVEL DRUG DELIVERY SYSTEMS FOR HERBAL DRUGS

INTRODUCTION

Herbal drugs are becoming more popular in the modern world for their application to cure variety of diseases with less toxic effects and better therapeutic effects. Novel herbal drug carriers cure particular disease by targeting exactly the affected zone inside a patient‟s body and transporting the drug to that area. Novel drug delivery system is advantageous in delivering the herbal drug at predetermined rate and delivery of drug at the site of action which minimizes the toxic effects with increase in bioavailability of drugs. In novel drug delivery technology, control of the distribution of drug is achieved by incorporating the drug in carrier system or in changing the structure of the

drug at molecular level. Incorporation of herbal drugs in the delivery system also aids to increase in solubility, enhanced stability, protection from toxicity, enhanced pharmacological activity, improved tissue macrophage distribution, sustained delivery and protection from physical and chemical degradation. For example, liposomes act as potential vehicles to carry anti-cancer agents by increasing amount of drug in tumor area and decrease the exposure or accumulation of drug in normal cells/tissues thereby preventing tissue toxicity effects. The phytosomal carriers have been studied for effective delivery of herbal extracts of Ginseng , Ginko etc. Direct binding of phosphatidylcholine to herbal extract components led to better absorption characteristics as compared to conventional delivery of herbal extracts. Other vesicular assemblies like microspheres, nanoemulsions, polymeric nanoparticles etc. have been proved beneficial to carry herbal components. The present review article is aimed

to provide an overview of different types of drug delivery systems incorporating active ingredients and potential advantages of such systems. In the present article, an attempt has been made to touch upon various aspects and applications related to novel herbal drug formulations.

                                 Types of Novel Herbal Drug Delivery Systems

·        Advantages of herbal drugs

1. Low risk of side effects

2. More Effectiveness

3. Lower cost:

4. Widespread availability

·        Importance of novel drug delivery systems in herbal medicines

Novel drug delivery system is a novel approach to drug delivery that addresses the limitations of the traditional drug delivery systems. Our country has a vast knowledge base of Ayurveda whose potential is only being realized in the recent years. However, the drug delivery system used for administering the herbal medicine to the patient is traditional and out-of-date, resulting in reduced efficacy of the drug. If the novel drug delivery technology is applied in herbal medicine, it may help in increasing the efficacy and reducing the side effects of

various herbal compounds and herbs. This is the basic idea behind incorporating novel method of drug delivery in herbal medicines. Thus it is important to integrate novel drug delivery system and Indian Ayurvedic medicines to combat more serious diseases. For a long time, herbal medicines were not considered for development as novel formulations owing to lack of scientific justification and processing difficulties, such as standardization, extraction and identification of individual drug components in complex poly herbal systems. However,

modern phytopharmaceutical research can solve the scientific needs (such as determination of Pharmacokinetics, mechanism of action, site of action, accurate dose required etc of herbalmedicines to be incorporated in novel drug delivery system, such as nanoparticles, micromemulsions, matrix systems, solid dispersions, liposomes, solid lipid nanoparticles and so on.Various drug delivery and drug targeting systems are currently under development to minimize drug degradation and loss, to prevent harmful side-effects and to increase drug bioavailability and the fraction of the drug accumulated in the required zone.

·        Advantages of novel drug delivery systems

1. Enhancement of solubility. 2. Increased bioavailability. 3. Protection from toxicity. 4.Enhancement of pharmacological activity. 5. Enhancement of stability. 6. Improved tissue macrophages distribution. 7. Sustained delivery. 8. Protection from physical and chemical degradation.

·        Types of Novel Herbal Drug Delivery Systems

Various approaches in case of novel herbal drug delivery system include different types of formulations as shown in the fig 1. such as liposomes, phytosomes, niosomes, transferosomes, ethosomes etc. are discussed below.

1. PHYTOSOME The term „Phyto‟ means plant while „Some‟ means cell-like. Phytosome is vesicular drug delivery system in which phyto constituents of herb extract surround andbound by lipid (one phyto-constituent molecule linked with at least one phospholipid molecule). Phytosome protect valuable component of herbal extract from destruction by digestive secretion and gut bacteria and because of which they show better absorption which produces better bioavailability and improved pharmacological and pharmacokinetic

parameters than conventional herbal extract.4 and the difference between phytosomes and liposome shown in fig 2.

2. LIPOSOME

Liposomes are concentric bilayered vesicle in which an aqueous volume is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids. The name liposome is derived from two Greek words: 'Lipos' meaning fat and 'Soma' meaning body. A liposome can be formed at a variety of sizes as uni-lamellar or multi-lamellar construction, and its name relates to its structural building blocks, phospholipids, and not to its size. A liposome does not necessarily have lipophobic contents, such as water, although it usually does. Liposomes are artificially prepared vesicles made of lipid bilayer. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Liposomes can be prepared by disrupting biological membranes, for example by sonication. Liposomes are micro particulate or colloidal carriers, usually 0.05- 5.0 μm in diameter which formspontaneously when certain lipids are hydrated in aqueous media. Liposomes are composed

of relatively biocompatible and biodegradable material, and they consist of an aqueous volume entrapped by one or more bilayer of natural and/or synthetic lipids. Drug with widely varying lipophilicity can be encapsulated in liposomes, either in the phospholipids bilayer, in the entrapped aqueous volume or at the bilayer interface and the drug encapsulated in liposomes shown in fig.3.

3. NIOSOMES are microscopic lamellar structures formed on admixture of a non-ionic surfactant, cholesterol and a charge inducing agent with subsequent hydration in aqueous media. Niosomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with a wide range of solubility‟s. Niosomes have been evaluated in many pharmaceutical applications. In such therapeutic applications, important advantages of using niosomes include their ability to reduce systemic toxicity by encapsulation of treatment agents and minimize clearance of such

agents from the body by slow drug release  and the structure of niosome shown in the fig 5.

Table 3: Applications of Niosomal Formulations

4. TRANSFERSOME

The term and concept of Transfersome were introduced in 1991 by Gregor Cevc. The name means “carrying body”, and is derived from the Latin word 'transferre',meaning „to carry across‟, and the Greek word „soma‟, fora „body‟. A Transfersome carrier is an artificial vesicle which resembles the natural cell vesicle. Thus it is suitable for targeted and controlled drug delivery. Transfersome is a highly adaptable and stress-responsive, complex aggregate.

It is an ultra-deformable vesicle which possesses an aqueous core surrounded by the complex lipid bilayer. Interdependency of local composition and shape of the bilayer makes the vesicle both self-regulating and self-optimising. This enables the Transfersome to cross various transport barriers efficiently, and then act as a drug carrier for non-invasive targeted drug delivery and sustained release of therapeutic agents. These self-optimized aggregates, with the ultra-flexible membrane, are able to deliver the drug reproducibly either into or through the skin, depending on the choice of administration or application, with high efficiency. These vesicular transfersome are several orders of magnitudes more elastic than the standard liposome and thus well suited for the skin penetration. Transfersomes over come the skin penetration difficulty by squeezing themselves along the intracellular sealing lipid of the stratum corneum. Flexibility of transfersome membrane is achieved by mixing suitable

surface-active components in the proper ratios. structure as shown in the fig.6. List of drugs used for Transfersomes shown in table 4.

Table4. List of drugs used for Transfersomes

6. ETHOSOMES

Ethosomes are the slight modification of well established drug carrier liposome. Ethosomes are lipid vesicles containing phospholipids, alcohol (ethanol and isopropyl alcohol) in relatively high concentration and water. Ethosomes are soft vesicles made of phospholipidsand ethanol (in higher quantity) and water. The size range of ethosomes may vary from tens of nanometers (nm) to microns (μ). Ethosomes permeate through the skin layers more rapidly and possess significantly higher transdermal flux.23as shown in the fig.7.

Future Prospects and Opportunities in India

India is one of the most strategic regions for the pharmaceutical market. Therefore many multinational giants have been keen to invest and grow preferentially in this sector.Developments in the new and advanced techniques in the field of NDDS will create huge demand for variety of excipients usage and development. India is well known for its quick adaptability to new excipients and associated technologies. So market for excipients in Indiawill grow on two aspects; one is in the form of exporting new organic excipients and the second one in the form of employing new excipients in various advanced delivery technologies. Majority of the pharmaceutical companies in the country have been applying and receiving new patents in the field of the Novel drug delivery systems. This eventually, in the near future derives huge demand for the products and services offered by pharmaceutical and allied businesses. Nanotechnology offers various modern applications in novel drug delivery systems that potentially improve the diagnosis, treatment and help monitoring of post-administration transformation of drug composition within the body systems. Another important milestone to be mentioned here is Computer aided Drug Design, which offers a lot of scope for the development of this kind of novel and advanced systems. Computer aided Drug Design helps in designing and developing the drugs and delivery systems consuming less time and resources with more accuracy and quality compared to traditional methods.