Oral Drug Delivery has just made a giant leap forward.  How did we do it?  Through “Spike” element conjugation and nano-encapsulation of therapeutically active agents.

Serum-Specific Drug Transport: Molecular Basis of

Tamarisk Technologies has revolutionized drug delivery with its development and clinical successes of the first serum-specific drug deliver vehicle. The Serum-Specific Nano-Encapsulate particles (SSNe) exhibit 100% resistance to both gastric and intestinal fluids. Upon oral administration SSNe particles pass freely, uninhibited, into the intestinal pool where they act like fat, look like fat, and breach the enterocyte membrane much more efficiently than micelle constituents.

The SSNe particle consists of a natural polymeric back-bone equipped with covalently linked C40 chains, referred to as the “Spike”. Upon drug encapsulation the polymeric back-bone forms multiple double-double helix aggregates which sandwich a therapeutic agent, whether macro- or micro in molecular structure, within helical cores which further cross-link to adjacent helixes to form spherical partices of 1-2nm in size with expossed “Spikes” protuding externally from the vehicle surface, similar to that of transmembrane protein protrusion from cellular membranes. It is these spikes which protect the particle and its therapeutic payload from gastrointestinal dissolution.

SSNe particles enter intestinal epithelial cells through simple diffusion across the plasma membrane. Although primary enterocyte entry follows simple diffusion, there is also evidence suggesting micelle interaction and cholesterol dependent NPC1L1 transport as a seconday mode of of SSNe entry.

Upon entry into the cytoplasmic space of enterocytes, intact SSNe particles associate with cellular constituients and are in turn transported together with fatty acids and monoglyceride through the endoplasmic reticulum and golgi apparatus where they associate with cholesterol, lipoprotein and other lipids for packaging within chylomicrons. SSNe containing chylomicrons are then extruded from the golgi apparatus into exocytotic vesicles, which are in turn transported to the basolateral aspect of the enterocyte. The vesicles fuse with the plasma membrane, undergoing exocytosis, dumping the SSNe loaded chylomicrons into the extracellular space. Virtually all steps in this pathway can be visualized using electron microscopy.

Next, rather than being absorbed directly into capillary blood, SSNe containing chylomicrons are transported into the lymphatic vessel that penetrates into each villus. SSNe chylomicron rich lymph then drains into the lymphatic circulation which rapidly flows into the blood. Blood-borne chylomicrons are rapidly dissociated freeing the SSNe particles which are likewise disassembled by serum components releasing the therapeutic payload directly into the bloodstream. SSNe particles have consistently and reproducible presented bioavailabilities of 93-97% of administered therapeutic agent, no matter the size or solubility of the molecule.

SSNe particles have been successful in the nano-encapsulation, oral administration and serum disposition of multipe therapeutic agents. Most recently Tamarisk successfully administered and clinically validated the therapeutic significance and broad spectrum of SSNe drug disposition through the nano-encapsulation of 5 therapuetic proteins: Insulin, Peptide YY3-36, EPO, Tumor Necrosis Factor and Herceptin. All of which presented, in triplicate, with >90% bioavailability of intact therapeutically active peptide within rodents. Human trials of SSNe Oral Insulin, Peptide YY, and Pegylated Interferon are currently underway.

At Tamarisk, we prefer to act rather than talk. Therefore, I continually challenge the industry to send me drugs of low or non-existent oral bioavailability and we will encapsulate them in our SSNe transport vehicle, at Our expense, and return them for evaluation.

The Holy Grail of Drug Delivery has Arrived………..questions, comments? I look forward to hearing from you. Follow Blog Click Here

 

Dr DeBrouse

Related Articles

3rd Party Evaluation Study of Resveratrol Encapsulated within Tamarisk's SSNe Drug Delivery - Click Here

(SSNe) Serum-Specific Drug Transport- Click Here

Oral Insulin Report- Click Here

Oral Peptide YY 3-36 - Click Here

Oral Tumore Necrosis Factor - Coming Soon

Oral Herceptin - Coming Soon

Oral Pegylated Interferon - Coming Soon

 

For more information about Tamarisk's Serum Specifc, Tissue Specific, and Extended Release technologies, contact the DelivRX team today at licensing@tamarisktech.com or call our office at 405-279-1250.

 

The documents on this web site could include technical inaccuracies or typographical errors. Please report any errors to Tamarisk Technologies Customer Service