Introduction:

Herbal medicines are used for treating various diseases since several centuries and we are using it as traditional medicine but still lacking in empirical data. In recent days there is tremendous growth in phytopharmaticeuticals, everyone is making their own medicine. Evidence based verification of the efficacy of poly herbal combination is still the need of an hour.

The world is emerging from micro to nano technology and we are still playing with the physiochemical properties of the herbs, rather than to know how fast compounds are absorbed after administration and which phytoconstituents are targeting which cells and what are the metabolic pathways of their elimination.

We should have sufficient data to prove that metallic poly herbal combinations are also safe. In Ayurveda we are using mostly “whole herb” without isolating its natural chemical constituents. Novel drug delivery system ensures the drugs exact target, increase bioavailability, efficacy and safety. The combination of ayurvedic herbs and novel drug delivery system with definitely bring a revolutionary change in efficacy and bioavailability of herbal drugs.

Aims and Objective:

To elucidate the novel drug delivery system.
To explicate the recent advancements in herbal medicines.

Drug Delivery System:

Drug delivery system means the approaches, formulations, technologies and system for transporting a pharmaceutical compound in the body as needed to safely achieve its desired therapeutic effect.

1) It should be scientific and site targeting.
2) Facilitating systemic pharmacokinetics.

DDS also involve 1) dosage form 2) route of administration.

Drug delivery technology modifies the techniques of drug release, absorption, distribution and elimination and increases the safety and efficacy.

There are various methods of drug release like diffusion, degradation, swelling, affinity based mechanism.

Route of Administration:

Various routes of administration are- oral, topical, trans mucosal (nasal, buccal, sub lingual, vaginal, ocular, rectal) and inhalation.

Bioavailability: The extent and rate at which the active drugs enters systemic circulation, thereby accessing the site of action.

Ayurvedic Drug Delivery System:

That can be classified as:

1) Solid- pills, gutika, vati
2) Semisolid- avleha, paka, lepa, ghrita
3) Liquid- asava, arishta, arka, tail
4) Powder- bhasma, satva, pishti, parpati, lavana, kshara, churna.

Draw Backs of Traditional System:

Poor patient compliance, increase chances of missing dose and unavoidable fluctuation of drug concentration- under/over concentration.

Novel Drug Delivery System:

It is the method of drug delivery that has significant efficacy with minimum dosage and maximum benefits.

It minimises the drug degradation and loss, and prevent harmful side effects, increases drug bioavailability and increases drug targeting.

Drug targeting is the potential to direct the drug loaded system to the site of interest.

1) Passive targeting
2) Active targeting

Different Carriers of Novel Drug Delivery System:

1) Liposomes
2) Microspheres
3) Nano particles
4) Phytosomes
5) Transferosomes
6) Ethosomes
7) Polymeric micelle formulation
8) Transdermal system
9) Implants
10) Micro pellets
11) Complexation
12) Nano/ micro emulsion

Advantages:

1) Increases solubility and bioavailability.
2) Protection from toxicity.
3) Improvement of pharmacological activity.
4) Enhancement of stability.
5) Improves tissue macrophages distribution.
6) Sustained drug delivery.
7) Protection from physical and chemical degradation.

Liposomes:

• These are colloidal and spherical vesicles (0.05 – 5.0 μm in diameter) composed of a bilayer membrane entrapping an aqueous core.

• There are constructed with polar lipids which are made up of lipophilic and hydrophilic group on the same molecules.

• Enhance product performance by increased solubility, bioavailability, targeting at site of action and prolonged release of drug.

• Topical application of the capsaicin liposomal formulation increase in the skin permeation as well as increased duration of action , inclusion of taxanes (antitumor activity) into the liposomes led to decreased tissue related toxicities of the drug with the increase in the efficacy of drug.

• Curcumin liposome, used in the treatment of cancer. Garcilin liposome used in lung disorders. Cathechin liposome also increases permeation through skin, anti oxidants and chemopreventive.

• Limitations: Low encapsulation efficiency, Rapid leakage of water-soluble drug in the presence of blood components and poor storage stability.

Microspheres

• It consists of spherical particles of size ideally 1-300 um.

• Each particle is matrix of the drug dispersed in the polymer and drug is released as a first order process.

• Polymers used for fabrication of micro particulate carriers such as albumin, gelatin, modified starch, polypropylene, dextran, polylactic acid and polylactide-co-glycolide etc

• Plant active ingredients such as rutin, camptothecin, zedoary oil, tetrandrine, quercetine and cynara scolymus extract has been made into microspheres.

• Immune microspheres and magnetic microspheres.

• Limitations: - poor entrapment and premature release.

Nano Particles

• These are colloidal systems with particles varying in size from 10 nm to 1000nm.

• They are in solid state and are either amorphous or crystalline, able to absorb or encapsulate a drug, thus protecting it against chemical and enzymatic degradation.

• Advantages:
  
             - Increasing compound solubility
             - Reducing doses.
             - Relatively increasing the absorbency of herbal medicines.

• Limitations:
  
             - particle-particle aggregation
             - Difficult in handling liquid and dry forms.

Phytosomes

• It is an emerging trend in delivery of herbal drugs and nutraceuticals.

• It is a formulation that incorporates standardized plant extracts or water soluble phyto constituents into phospholipids to produce lipid compatible molecular complexes.

• It improves absorption and bioavailability of herbals.

• It is useful as in case of flavanoids, tannins, and terpenoids.

• E.g is green tea phytosome used as systemic antioxidant. Grape seed phytosome as cardio protective. Curcumins phytosomes as antioxidants and anti cancer.

• Limitation is their bioavailability when administered orally or topically.

Transferosomes

• It is a phospholipid vesicle which acts as powerful carriers.

• It is a potential Transdermal delivery of the curcumin.

• It is chemically unstable and its purity is under question.

• They are very expensive

Ethosomes

• It is a vesicle composed of phospholipids and high concentration of ethanol.

• Improved drug delivery to deeper layer of the skin and even to blood.

• It is useful for topical delivery of alkaloids.

• Unstable and skin poor permeation limits their utility.

Micro Emulsion

• These are multiple emulsion having the size range of several microns.

• Useful in trans dermal delivery system,

• Non-toxic and non irritant

• Nano emulsions are useful in delivering drugs to cell culture, cancer therapy and as disinfectants.

• It increases solubility and bioavailability of the drug.

• Palatability and compatibility with other excipients is a limiting factor in the case of oral drug therapy.

Polymeric Micelle

• Polymeric micelle consists of an inner hydrophobic core capable of solubilizing lipophilic substances and an outer hydrophilic corona which serves as the stabilizing interface.

• It is used to carry a number of drugs like Artemisinin form Artemisia annua L and Curcumin form the roots of Curcuma longa L are used as Antimalarial drug.

• Polymer Sodium dodecyl sulfate led to 25 fold increase in solubility.

• Limitations: Poor physical stability and potential for embolism.

Transdermal Delivery

• These are the devices in which drug present in the formulation permeates into the systemic circulation by diffusion to stratum corneum and further to the effected organ.

• These devices use polymer matrix, adhesive bandage and permeation enhancers.

• Advantage: controlled drug delivery, enhanced bioavailability, reduction in side effects and easy application.

• Transdermal delivery of herbal drugs are to increase the penetration and sustained action.e.g.transdermal films containing boswellic acid ( Boswellia serrate) and curcumin (Curcuma longa) were formulated for the treatment of inflammation (synergistic effect).

• Limitations are hepatic first pass metabolism, increased therapeutic effect, and maintenance of steady state concentration in the serum.

Implants

• It is used for controlled and sustained action of the drug

• Devices are directly placed in the body fluids/cavities by mean of a microsurgery

• They are fabricated by using biodegradable polymers e.g. chitosan and gelatin.

• Non biodegradable polymers may cause irritation.

• Implants of the extract of danshen (Radix salvia Miltiorrhizae) used for healing of muscles and tissues in the abdominal cavities.

• Activity may last for 28 days,that prevents the patient from frequent dosing.

Micropellets

• These are used for the delivery of drugs (1-1000 µm) to specific sites and for the extended period of time

• Used for the delivery of the two incompatible drugs simultaneously.

• Pellets are used for the coating and taste masking of the formulations.

• Pectin-hydroxypropyl methylcellulose (HPMC) coated curcumin pellets were prepared for delivery of the curcumin in the colon to treat the inflammatory disease.

• Pectinolytic enzymes helps in releasing drug in the colon, and avoids vomiting, loss of appetite and nausea.

• The limitations are bioavailability and site specific drug delivery.

Complexation

• It is the association between two or more molecules to form a non bonded entity with well-defined stoichiometry.

• Various complexing agents such as EDTA, cyclodextrins and polymers have been used for the complexation

• The solubility of the curcumin was increased by the formation of the Curcumin soya lecithin complex and evaluated for the hapato-protective activity.

Conclusion:

1) Novel drug delivery system of herbal drugs has potential future for enhancing the activity and overcoming problems associated with plant medicines.

2) Nanotechnology, from the very beginning, has been very successful in overcoming the hurdles offered by conventional therapy. Target specific nature of the delivery systems developed applying nanotechnology principles have been able to reduce the amount of drug that needs to be loaded and hence prevent many dose-related adverse reactions. Currently, not many products are available for clinical use, but looking at the amount of research activity happening in this field, the next few years will witness the outburst of nano-medical devices, therapeutic aids, and many products being launched in the market for clinical use. Though initially the cost of therapy may be presumed to be beyond the reach of common Indian population, but soon more and more economical devices and therapies shall be available. The field of nanotechnology yet remains to be explored to its fullest; as a result many more advanced products will be soon available.

Approved products of nano technology:

Due to the stringent food and drug act (FDA) regulations, only a few products based on nanotechnology are available for clinical use. Doxil® (Centocor Ortho Biotech Products L.P, New Jersey, USA.) and Abraxane® (Abraxis Bioscience, Los Angeles, USA.) are among the two available for clinical use. Doxil®, approved by FDA in 1995, was originally developed to treat HIV-related Kaposi's sarcoma and has now evolved as a second-line treatment for ovarian cancer and multiple myeloma. Doxil®, a reformulation of doxorubicin, with the drug encased in a PEGylated liposome, increases its functionality and specificity while decreasing its cardiotoxicity. Abraxane®, developed for the treatment of breast cancer, comprises the drug, paclitaxel encased in an albumin shell (.ref- chronicals of young researches.)

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