Ancient wisdom modern methods

There is a revival of interest in the properties of ingredients of traditional medicines and some of them have already proved to be superior excipients and forming the basis for better drug delivery systems. Arun Kedia, Managing Director, VAV Life Sciences, reveals more details of this come back saga

The overuse and abuse of modern synthetic drugs combined with the risk of side effects has created a bottle neck in the world of medicine. Today ancient medicines are making a comeback and combined with the technological advances in the processing and isolation of active compounds, they hold a promise of meeting the challenge of the numerous chronic conditions modern life has created.

Ancient medicine is also a way of life that teaches how to maintain and defend health. While contemporary medicine continues to have a valuable place, many are opting for old medicines and remedies.

It may not be possible to exactly determine the beginning and rise of ancient medicine but it surely has had thousands of years to experiment. Historically, remedies were discovered largely by chance. There were no placebo-controlled, double-blind studies to evaluate the efficacy. It was largely a process of trial and error that stretched over many millennia. What scientific evidence does exist today for evaluating the efficacy is largely supportive. On the other hand, synthetic medicines that are launched into the market are mandatorily supported by large scientific data in terms of clinical trials done on animals and then on humans.

Many may feel that patients seeking alternative medicine could be misled into believing they are being cured when little or no documented scientific evidence exists to support the effectiveness of the treatments on offer. However, it is important to note that no clinical documentation does not necessarily translate into ineffectiveness.

Often it more directly translates into a lack of commercial incentives for extensive study. Also, the support generated for the synthetic drugs through clinical trials does not guarantee long-term safety. A drug is proven to be safe and effective but it is only so for a limited period of time until the study is completed.

Ancient medicines, on the other hand have the advantage of being supported by data analogous to clinical trials that have accumulated over time. Supporters of ancient medicine are using the weapons of these clinical trials and peer-reviewed studies to undermine this wall of skepticism.

This article focuses on the role of (soya and egg) lecithin, and egg yolk oil, in helping shape modern day drug delivery systems.

Medicinal properties of soyabean and egg; re-discovered in the form of soya lecithin and egg lecithin
Soybean is a sweet cooling and slightly bitter herb used in treating a variety of ailments since centuries. Soy lecithin is an all-natural complex of phospholipids that is made up from oil extracted from the soybeans. Health benefits of lecithin include natural weight loss, natural removal of fatty deposits from our body, facilitation of digestion by stimulating bowel function, natural protection of liver, naturally reduced cholesterol levels, improved, mental performance natural prevention of neurological diseases like Alzheimer’s and dementia.

Soya lecithin is an excellent source of choline. Lecithin physically is made in our liver, and is
necessary for every cell in our bodies.  Without choline, the membranes of our cells would
harden, which would prevent nutrients from entering and leaving the cell.

Soya lecithin also helps cholesterol deposits from forming in our blood vessels, and is involved in the process of moving cholesterol through our bodies. lecithin has a selective action on the lipoproteins that carry cholesterol in the blood, it reduces high levels of lipoproteins LDL while raising the level of HDL lipoproteins favoring the removal of excess cellular cholesterol.

Lecithin also helps keep a smooth transmission of nerve impulses and therefore it becomes a valuable restorative for our nervous system and this is the reason how soya lecithin helps in improving memory and mental performance. Moreover, phosphatidylcholine contained in lecithin is important for the formation and maintenance of brain neurotransmitters between neurons, as it exerts a major action on each stage of memory development and mental activity and performance.

Lecithin phospholipids protect the liver cell membranes, therefore, preventing accumulation of fatty deposits in the liver. It also helps the liver in prevention of abuse-related disorders like alcohol and drugs harmful for the liver.

Highly bioavailable minerals present in lecithin namely iron, calcium, phosphorus, magnesium, sodium, potassium, and some trace amounts of zinc, selenium, copper, and strontium are recommended for use in food for prevention of cerebral vascular accident and reduction of risk of thrombus formation.

• Egg yolk oil – Egg yolk oil is a very rich source of lecithin. LIPOVA – E120 is fat free egg lecithin with 93 per cent phospholipids. Purified egg lecithin makes for an attractive excipient for drug delivery since it can be totally bio degraded and metabolised as it is an integral part of biological molecules. It has been given GRAS or Generally Regarded As Safe status by FDA. The absorption of a given drug depends on the balance of its solubility in the aqueous environment of the gastrointestinal lumen and its capability to diffuse across the lipophilic apical membrane of enterocytes. Generally, drugs have to be dissolved in order to attain sufficient bioavailability. Egg lecithin may improve the oral bioavailability of poorly water soluble drugs by a number of possible mechanisms. They can increase effective drug solubility in the GI tract and blood vessels by stimulating the secretion of bile salts and endogenous biliary lipids such as phospholipid and cholesterol, forming intestinal mixed micelles, and then increases the solubilisation capacity of the GI tract. Moreover, as a result of the intercalation of administered phospholipids into these bile salt structures, either directly or by secondary digestion, micelle structures swell up and lead to a further increase in solubilisation capacity. Egg lecithin can also increase the gastric retention time, resulting in slow delivery to the absorption site and increased time available for the absorption.

Oral drug delivery systems

• Liposomes – Liposomes are aqueous compartments enclosed by lipid bilayer membranes. The liposome, first introduced by Bangham et al. In the 1960s, has been successfully developed as lipid based drug delivery vehicle. Liposomes can be prepared from lecithins by a simple thin film hydration method. Water-soluble drugs can be trapped inside the aqueous compartment of liposomes. However, water-insoluble ones can be incorporated into the bilayer membrane. Liposomes have been designed to reduce side effects of incorporated drugs and to enhance the therapeutic efficacy. Liposome structure can be adjusted to control release of the drug. Also, the surface of the liposome can be modified with polyethyleneglycol (PEG) to increase the residence time in the bloodstream and decrease recognition by the immune system. Such a modification also slows down the clearance of the liposome from the system.

Transdermal drug delivery systems

• Transferosomes – Despite all the efforts devoted by several researchers, it was impossible to formulate a liposomal compound that permits the systemical release of an active principle, mainly because the dimension of the liposomes does not allow them to penetrate the stratum corneum.
  Transferosomes are a special type of liposomes, consisting of phosphatidylcholine and an edge activator. The concept of transferosomes was introduced in 1992 by Cevc and coworkers. These vesicular transferosomes are several orders of magnitude more elastic than the standard liposomes and thus well suited for the skin penetration. From the composition point of view, a transferosome is a self adaptable and optimised mixed lipid aggregate. Transferosomes are vesicles composed by phospholipids as the main ingredient (soya phosphatidylcholine: LECIVA-S70, egg Phosphatidylcholine: LIPOVA-E120, dipalmityl phosphatidylcholine, etc), 10-25per cent surfactants for providing flexibility  like sodium cholate, 3-10 per cent alcohol as a solvent (ethanol, methanol) and hydrating medium consisting of saline phosphate buffer (pH 6.5-7).

Parenteral drug delivery systems

• Fat emulsions – Intravenously administered oil in water emulsions containing triglycerides as the dispersed phase and egg lecithin as the preferred emulsifier are common in intensive care medicine. Parenteral fat emulsions can be used as potential carriers for poorly water soluble drugs. Drug emulsions are normally formulated to be isotonic, and the amount of dissolved components can be minimised because the drug is in the lipid phase.  A good example of the system is the intravenous anaesthetic propofol (Diprivan) which has been considered as one of the most successful fat emulsions applied to drug delivery systems so far. It comprised of soyabean oil in which propofol can readily dissolve, egg lecithin as an emulsifier and glycerol which maintained it isotonic to blood. The pain on injection was reduced since the concentration of propofol to be administered decreased. A decrease in toxicity, together with an increase in the therapeutic window, is another potential advantage. Different combinations of emulsifiers like egg lecithin (LIPOVA-E120), egg lecithin plus soya lecithin and soya lecithin alone have been used in preparation of fat emulsions.

Egg yolk oil
Egg oil also has its reference in Alchemy (originated circa 400 BC) in regard to its effectiveness in regeneration of skin and cell membranes. Egg oil is rich in essential poly unsaturated fatty acids  (PUFA) known like Omega-3 & Omega-6. Egg oil is suitable for the following applications:

• Hair care – In Indian, Japanese, Chinese and the 2000-year-old Unani-tibb or Greek system of medicine (Roghan Baiza Murgh), egg oil was traditionally used as a treatment for hair care where it arrests hair fall, promotes new hair growth and retards greying. It helps in repairing damaged hair due to chemical treatment and hair loss due to stress, fever, dandruff and antibiotics.
• Skin care – Egg oil can be used as an excipient/carrier in a variety of cosmetic preparations such as creams, ointments, sun-screen products or lotions where it acts as an emollient, moisturiser, anti-oxidant, penetration enhancer, occlusive skin conditioner and anti-bacterial agent. It also helps the texture, lubricating and anti-friction properties of creams and lotions for skin. As an occlusive agent, it protects against dehydration without disturbing the pores and is easily incorporated in topical preparations since it forms stable oil in water emulsions.
• Wound and burn care – Egg oil has been used in treating wounds and injuries since centuries. Ambroise Paré used a solution of egg yolk, oil of roses, and turpentine for war wounds, an old method that the Romans had discovered 1000 years before him. He published his first book ‘The method of curing wounds caused by arquebus and firearms’ in 1545. It aids faster healing by re-epithelisation, keeping the wound sterile due to its anti-bacterial action and minimises scars. It is a natural emollient, and can be used externally on burns, it reduces pain and promotes re-epithilisation while minimises scars. It is also a useful first aid treatment for immediate pain relief and prevention of blisters. The essential fatty acids of the yolk are responsible for the reduction in catabolism as well as increased matrix synthesis and promotion of new skin growth. As opposed to skin grafting, egg oil does not change the texture of the new skin. It is also useful in treating burns caused by radiations such as those caused during cancer treatment.

VAV’s product line is a representation of how ancient cures like lecithin  (egg and soya) and egg yolk are now playing vital roles in developing more efficient excipients and drug delivery systems.