BioPharma’s NanoSorb delivery technology will put your products ahead of the times”!

2. BioPharma’s NanoSorb delivery technology will put your productsahead of the times”!

3. Small Unilamellar Vesicle (SUV) Large Unilamellar Vesicle (LUV) Multilamellar Unilamellar Vesicle (MLV) What is a Liposome ? Typical Size Ranges: SLV: 20-50 nm – MVL:100-1000 nm

4. Oral Liposomes Rationale Liposomes can carry a wide variety of agents Liposomes protect the gents they carry from degradation by metabolic processes Liposomes starting material (phospholipids, other non-polar lipids) can assist in solubility Liposomes can enhance absorption

5. Electron Micrograph Freeze-Fracture

6. Liposomal Preparation Optical Microscope (x400)

7. Liposomes Cryo-Microscopy

8. H2O Layer Lipid Layer Cross-Section of a Liposome Polar Lipids (Phospholipid) Lipid Soluble ingredients (Drugs, Nutrients & vitamins) Water Soluble ingredients (Drugs, Nutrients & vitamins)

9. Oral Liposome & GI Interaction

10. Liposomes: Historical Review The First 10 Years Discovered 35 years ago (1961) Biological and chemical properties explored The Middle Years (1975 to 1990) Liposome physical characterization Discovery of several types of liposomes Techniques for liposome sizing Pharmaceutical and pharmacological rationale that justify use of liposomes Safety testing

11. Liposomes: Historical Review (cont.) Recent Developments (1991 to present) Scaling up and production of topical preparations Stability issues overcome First clinical trials Commercialization of liposome products The Future Continued R&D, new applications More sophisticated liposome products Oral Delivery Systems

12. Major Modes of Liposomal Actionand Related Applications Mode of Action Application • Intracellular uptake : • lysosomes • endosomes • cytoplasm Microbial diseases Metal storage diseases Gene manipulation Specific Cancer Cell Targeting Vaccines [efficient antigen presentation] Slow release of drugs near the target area Tumors near fixed macrophages Avoidance of tissue sensitive to drugs Cardiotoxicity of doxorubicin Circulating reservoirs Blood surrogates Enhanced absorption and bioavailability! Delivery to skin, lungs, eyes, mucosal tissues, GI tract

13. Liposomal Delivery PROS Enhanced Solubility Sustained Release Specific targeting – “Magic Bullet” CHALLENGES Stability, Sterility, Retention (leaks) WHY LIPOSOMES? Biocompatible Non-immunogenic Biodegradable Non-toxic

14. Oral Liposome Stability Major Obstacles • Stomach pH • Bile Salts • Enzymes-Lipases • Clinically useful liposomes • must be stabile in vitro and in vivo

15. Oral Liposomes Advantages Direct Drug or nutrient stability and protection Enhanced absorption of hydrophobic molecules Enhanced absorption of encapsulated ingredients Protein and Polypeptide protection Decreased irritation to stomach lining from surface active drugs Sublingual: direct absorption (bypass liver metabolism)

16. Oral Liposomes Advantages Indirect Beneficial effects of Lecithin Synthesis of neuro transmitters Manufacturing of sterol hormones Important role in fat transport in and out of cells Can lower LDL and VLDL

17. New NanoSorbTM: BioPharma’s Spontaneous Liposome Technology! • Patented NanoSorb LiposomesTM • Form and encapsulate spontaneously with water • Eliminate degradation, denaturization • Eliminate stability, retention and storage problems • Reduce production costs up to 90%!

18. Human milk is rich in liposomes! Thin Section

19. Fat Content of Human Milk 4% Total Fat Content Major Fat Components Triacylglycerols 98% Phosphosphlipids 1-2% The colloidal structure of milk is still not fully understood though clearly glycerols are favored over phospholipids. NanoSorb Molecule has similar components!

22. NanoSorbTM Liposome Applications Functional Food & Capsule Nutrition Delivery Topical Transdermal Delivery Sublingual Delivery Long Circulating Liposomes for Systemic Delivery via multilaminar liposomes

23. NanoSorb Applications

24. Nanosorb nanotechnology is unique in that it forms nanosized liposomes that encapsulate spontaneously upon the addition of water, without standard heating, cooling and agitation methods used for ordinary liposomes! Our new patented technology is therefore much more economical, while providing minimal potential for degradation, especially with highly sensitive bio-active nutraceuticals. Uniqueness of the NanoSorb Molecule

25. Gentle Encapsulation With NanoSorb Encapsulation with NanoSorb demonstrating no diminution of antioxidant activity

26. NanoSorb Liposomes Encapsulate More Effectively The NanoSorb molecule also encapsulates ingredients more effectively than “old tech” liposomes, as the chart below demonstrates: Comparative encapsulation % profile of CoQ10 for 3 months at room temperature

27. NanoSorb Bioavailabilty is Greater CoQ-10 nano-encapsulated with NanoSorb liposomal tech is also more bioavailable than standard liposomal CoQ-10

28. “NanoSorbTM in Gel Capsules” + LipoCeuticals Soft Gel = NanoCaps

29. NanoSorb Gel Cap Applications • Pharmaceuticals • Nutraceuticals • OTC

30. Convenient lower dosage form Initial protection from stomach environs Liquid dosage form Pre-dissolution of dry substance Faster onset potential Greater bioavailability Advantages of NanoSorb Gel Caps

31. NanoSorb Gelcap Benefits • Enhanced Absorption and Bioavailability of medicines, nutraceuticals, vitamins, proteins, peptides • Increased Effectiveness at existing dose • Sustained Release of ingredients • Protection of acid labile drugs/nutraceuticals

32. Bioavailability of Vitamin E w/ NanoSorb Gel Caps

33. Bioavailability of Vitamin B12

34. The NanoSorb delivery system also delivers a greater amount of the active ingredients through the skin as compared to conventional vehicles. Improved Dermal Penetration Comparative study showing the amount of caffeine that penetrates through the layers of skin at eight hours. Topical Penetration Study: Penetration = Efficacy

35. New Delivery Oral Delivery System NanoSorb SublingualNutrient Delivery Old Delivery The Digestive System

36. Transmucosal Delivery NanoSorb Spray Traditional Spray • Penetration • is greater • Better • penetration allows for decreased dose in some cases • Greater • concentration in submucosal tissue • Higher • concentration in bloodstream Mucosa Submucosal Tissue Connective Tissue Bloodstream

37. NanoSorb Sublingual Spray® The therapeutic effect of a nutrient is directly related to the quantity and rate at which the unchanged nutrient reaches the bloodstream

38. Oral NanoSpray vs. TabletBioavailability Model

39. Sublingual / Oral vs. Capsulestwo-piece Gelatin Capsule

40. Increased Bioavailability

41. NanoSorbTM “Lipo-Ceuticals” The most effective form of nutraceutical, cosmeceutical and pharmaceutical delivery to maintain product competitiveness!