CONTRACT MANUFACTURING Encapsula has recently completed the construction of a 2300 square foot manufacturing facility which is registered with the United States Food and Drug Administration (FDA Registration Number 15414387686) and approved by the USDA. The facility is set up based on FDA cGMP food manufacturing guidelines.

The production line begins with a temperature-controlled, high shear mixing system which is the key to manufacturing liposomes of the desired size. Once the liposome batch is prepared, we offer a variety of packaging options for our clients. We specially selected our filling equipment to be as versatile as possible in order to provide our clients with a wide range of liposome product concentrations from creams to liposome-based drinks. We can provide bulk-packaged liposomes so that the clients may mix the liposomes into their own proprietary commercial formulation. Or, we can package the final liposomal product in single-use foil pouches, multiple-use bottles (i.e. pump delivery) or drink-type bottles. For bottles, we can complete the packaging with the now popular and colorful shrink-wrap sleeves of the client's own design.

Our current facility can accommodate batch sizes of 10 liters to 1000 liters (~2.5 gallons to 250 gallons) potentially running multiple batches per day depending on the batch size and packaging requirements.

Our manufacturing methods do not utilize chlorinated or any other organic solvents such as ether, methylene chloride and chloroform. The use of these solvents in conventional liposome preparation both in the lab and in pharmaceutical manufacturing facilities represents a significant cost in both equipment and safety requirements as well as in the disposition of large quantities of these solvents. The cost reduction due to the absence of organic solvents coupled with the significant reduction in the cost of higher purity soy (rather than egg) phospholipids allows Encapsula to manufacture liposomes at a much lower cost than the marketed pharmaceutical liposomal formulations. Therefore we can provide liposomal formulations of nutraceuticals, cosmetics and food additives at a price that can be competitive with other products in these industries.

If you have your own formulation and you would like us to manufacture and package your liposome based product that is used in food, nutraceutical or cosmetic industry then please contact us at info@encapsula.com to discuss the project.

Encapsula NanoSciences does not manufacture any injectable liposome formulations for pharmaceutical companies or for clinical trial applications.

Liposome based drugs have been used intravenously in the pharmaceutical industry for many years. Liposomes have also been used extensively in the cosmetic and skin care industry for delivering compounds into the deeper layers below the surface of the skin. For more information on this subject, read the section below on "Liposomes in Cosmetics".

Oral delivery of liposomes- a very new field in liposomology- has been recently investigated. Initial studies have shown that coated liposomes and mucoadhesive liposomes are very promising technologies for oral delivery of molecules such as insulin and calcitonin. For more information on this subject, read the section below on "Liposomes in Nutraceuticals".


Liposomes in Nutraceuticals

Data from a small pilot study has indicated that the use of coated liposomes provides a sustained release of certain muscle-building amino acids in the bloodstream when taken orally. These liposomes are being incorporated into a sports drink targeted to bodybuilders and others engaging in extreme physical activity. Obviously if liposomes can provide a sustained release of amino acids from drinkable formulations, there is huge potential for the delivery of other amino acids such as creatine, arginine and glutamine all of which are widely used in the bodybuilding and sports arenas. More importantly, oral liposomal delivery may enhance the absorption as well as provide a sustained release of many vitamins, minerals, antioxidants, etc. resulting in the higher or sustained serum levels which is required for the plethora of pharmaceutical indications for nutraceutical compounds. Animal studies data shows that coated liposomes can protect proteins such as insulin and calcitonin from the deleterious effects of gastric fluid resulting in a pharmacological response (i.e. reducing blood glucose and calcium levels, respectively) when dosed orally. Encapsula's proprietary version of these liposomes, ENCAPSOME^TM, can be used to encapsulate many nutraceuticals into the liposomes for oral delivery.

Liposomes have the unique property of being capable of carrying both water-soluble and oil- or fat-soluble compounds within a single particle. Dispersing fat-soluble nutrients in water or water-based drinks is one of the most problematic issues that nutraceutical manufacturers face. However, using a liposomal system, for example, water-soluble B vitamins may be encapsulated in the aqueous compartment of a liposome while the fat-soluble omega-3-fatty acids (i.e. EPA, DHA) and/or vitamin E can be incorporated into the membrane of the liposome. Thus, a single ENCAPSOME^TM formulation of both types of compounds can be easily admixed with a variety of foods and drinks such as juices, smoothies or plain water without concern about the oily compounds forming unappetizing globules in the product. Liposomes are also reported to eliminate the fishy odor and taste usually associated with the omega-3-fatty acids isolated from fish (the preferred source of these nutrients).

Liposomes, or lipid nanoparticles, also have a particular advantage in nutraceuticals, that is, the phospholipids themselves, specifically phosphatidylcholine (PC) and phosphatidylserine (PS) are extremely popular supplements on their own. PC has been reported to assist in restoring liver function in disorders such as alcoholic fibrosis and viral hepatitis. In animals, PC has been shown to provide a substantial hepatoprotective effect when the animals were fed a high-alcohol diet. Small clinical studies have shown that supplementation with PC significantly reduced symptoms and decreased time to normal liver function tests in cases of hepatitis A, B and C.

PC is also an accepted form of choline for the purposes of supplementation. Synthetic choline salts are poorly absorbed and can cause a fishy-odor to emanate from those who take choline salts. Increased choline uptake has been recommended for pregnant and nursing women by the Food and Nutrition Board of the National Academy of Sciences in order to ensure normal fetal brain development and choline is added to some infant formula. In fact, the FDA has set a recommended dose for choline at 550 mg based on policies set by the National Research Council of the National Academy of Science. Following is the statement from the NAS:

"Choline functions as a precursor for acetylcholine, phospholipids and the methyl donor betaine. The primary criterion used to estimate the Adequate Intake (AI) for choline is the prevention of liver damage as assessed by measuring serum alanine aminotransferase levels. The AI for adults is 550 mg/day of choline for men and 425 mg/day for women. There are no nationally representative estimates of the intake of choline from food or food supplements. Choline in the diet is available as free choline or is bound as esters such as phosphocholine; glycerophosphocholine, sphingomyelin, or phosphatidylcholine. The critical adverse effect from high intake of choline is hypotension, with corroborative evidence on cholinergic side effects (e.g., sweating and diarrhea) and fishy body odor. The Tolerable Upper Intake Level (UL) for adults is 3.5 g/day."

Therefore, claims such as "Excellent source of choline" or "Rich in choline" may be added to the packaging.

PS is rapidly gaining scientific support as a nutritional supplement which can improve both cognitive and memory functioning in various types of Age-Related Cognitive Decline (ARCD) such as Alzheimer's Disease. PS is necessary for effective neurotransmitter function in the brain and other neural tissue. With the sweeping efforts to reduce fat in the diet, essential phospholipids such as PC and PS are being eliminated from the diet as well, therefore supplementation is necessary. An extensive discussion of the studies showing the positive results of PS supplementation in Alzheimer's and other ARCD conditions may be found at www.leci-ps.com/bioactives/html/e/products/brands/lecips/app.htm along with some data and speculation as to how both PC and PS may be useful in physical exertion such as that seen with professional athletes.

The FDA last reviewed the clinical data on the use of PS supplementation in ARCD in 2003 and concluded that the data supported the following claims, but only with the associated disclaimer.

Dementia claim and disclaimer:
"Consumption of phosphatidylserine may reduce the risk of dementia in the elderly. Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of dementia in the elderly. FDA concludes that there is little scientific evidence supporting this claim."

Cognitive dysfunction claim and disclaimer:
"Consumption of phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly.
Very limited and preliminary scientific research suggests that phosphatidylserine may reduce the risk of cognitive dysfunction in the elderly. FDA concludes that there is little scientific evidence supporting this claim."

We believe that once multicenter, controlled and blinded clinical trials are conducted, the use of PS to treat, and perhaps prevent, ARCD will become universal.

Encapsula NanoSciences can provide the specific expertise required to determine the best type of liposome along with an optimized manufacturing process to nutraceutical companies who are ready to enter the field of lipid nanoparticle technology.


Liposomes in Cosmetics, Cosmeceuticals and Nutricosmetics

Lipids and liposomes (lipid nanoparticles) are being used extensively in cosmetic formulations and have been for more than 20 years. The most common cosmeceutical (a topically applied nutraceutical for cosmetic purposes) is a liposomal formulation of vitamins A, C and E. The next wave of nutraceutical applications in the cosmetic industry is known as nutricosmetics, or orally ingested nutraceuticals which show an effect on the skin, hair and nails. Nutricosmetics have already hit $1 billion worldwide primarily in Europe and Asia and are projected to experience double-digit growth over the next 5 years (Kline & Co., 2006); this growth is primarily attributed to the baby-boomers who are aspiring to both look and feel better as they age. With nutricosmetics themselves being new to the North American market, competition will be fierce to market a superior formulation. With ENCAPSOME^TM-encapsulated nutraceuticals, your product will have a marketing as well as a performance edge on your rivals. See our section on liposomal nutraceuticals for a detailed description of how liposomes enhance the absorption and release of nutraceuticals into the bloodstream after ingestion.

As with cosmeceuticals, liposomal formulations of the antioxidant vitamins A, C and E will be popular for oral consumption. In addition to the oral delivery advantage that liposomes have to offer, vitamins A and E are not water soluble and therefore are more difficult to add to a water-based, drinkable formulation. However, vitamins A and E along with many other antioxidant cosmeceutical compounds such as CoQ10, lycopene and other carotenoids can be inserted into the liposomal membrane which both increases their chemical stability and physically makes them easily and stably dispersible in water. Liposomes are uniquely suited for delivery of nutraceuticals because of their ability to deliver water-soluble compounds in the same particle as water-insoluble compounds. Many other nutraceutical antioxidant compounds are water soluble such as vitamin C, superoxide dismutase (SOD) and glutathione, therefore the same liposome that carries vitamin E and CoQ10 may also contain SOD in its aqueous compartments. See our section on the technical description of liposomes for a more thorough description of the biophysical properties of liposomes and how lipophilic compounds are incorporated into the hydrophobic liposomal membrane and hydrophilic compounds encapsulated into the aqueous compartments simultaneously.

Topical formulations of liposomal compounds for cosmetic purposes remain popular with our clients and their customers. Lipophilic compounds such as cholesterol and ceramides, which have been used in topical skin creams for many years because they are lipids found in normal skin tissue, are easily incorporated into liposomes. In addition to the ubiquitous vitamin A, C, E and other antioxidant liposomal formulations, our clients are asking us to formulate more sophisticated compounds into liposomes for cosmetic purposes such as peptides which aid in wound healing and reduce scarring as well as new biological compounds which have been shown to protect the skin against sun, heat and chemical damage. Encapsula welcomes the challenge to develop novel formulations from such compounds which will not only enhance the delivery of the compounds to the skin but also provide the client with patent protection for the new product.

Another popular application for topical liposomes is in prevention of hair loss and hair regrowth. SOD along with Minoxidil^® and Retin-A^® among other compounds have been incorporated into liposomes for such applications. This is another active area of research in which new compounds are frequently being shown to affect hair growth and liposomes have long been known to deliver compounds to the hair follicle making them an obvious choice for enhancing the delivery and maintaining a sustained release of these new compounds to the site of action for many molecules.

Contact us at info@encapsula.com or 615-884-4442 to discuss either manufacturing conventional liposomal cosmetic products or the development of new liposomal cosmeceuticals and nutricosmetics.