Title: Non-Invasive Delivery of Peptides: Advances in Oral Delivery

Biography:

Nozer Mehta Peptide Technologies, LLC, USA well recognized leader with 30 years of experience in the development of peptide-based therapeutics, and an inventor on 28 issued patents and numerous applications. Excellent communication, team building and leadership skills. Proven scientific leader for internal projects, as well as collaborative teams with several external companies across multiple therapeutic areas, including osteoporosis, osteoarthritis, obesity and diabetes. Experience with presentations at major international conferences and to pharmaceutical companies, and internally to the Board of Directors. An area of extensive preclinical and clinical development expertise is the oral delivery or peptides and certain classes of small molecule drugs. Additional areas of competency include recombinant expression technologies for peptides, novel target identification, validation, and preclinical and clinical development of peptide drugs.

Abstract

Non-invasive peptide delivery routes such as oral, buccal, nasal, pulmonary and transdermal offer several advantages including safety and ease of use for the patient, and the potential for increased physician acceptance and patient compliance for chronic indications. Oral delivery remains the most extensively studied non-invasive route, but it presents numerous biological challenges. Of the few oral peptides currently marketed, most are intended for localized intestinal delivery or represent peptides with special characteristics. Absorption of orally delivered peptides into the systemic circulation generally occurs in the duodenum or lower regions of the small intestine. The intestinal epithelium and the mucus layer offer a barrier to the transport of molecules greater than 2 to 3 amino acids in size, and intestinal proteolytic enzymes derived either from the pancreas or from the intestinal brush border membranes rapidly cleave peptide bonds. For most peptides, these challenges of poor intestinal permeability, susceptibility to proteolytic degradation, as well as their short half-life, propensity to aggregate, and other limitations need to be overcome by formulation or peptide structure modifications to increase bioavailability and develop commercially successful products. Strategies such as cyclization, addition of unnatural amino acids, and blocking of N- and C-termini to stabilize peptides and increase their protease resistance, are examples of beneficial structural modifications. The addition of protease inhibitors and permeation enhancers to the formulation, conjugation to peptide transporters, and encapsulation in robotic pills or micro- and nano-spheres are also widely used techniques. However, further increases in bioavailability, decreases in inter- and intra-patient variability, elimination of food effects, and confirmation of long term safety of formulation excipients remain as foci for further efforts to fully realize the potential for oral delivery. A variety of peptide molecules are currently in pre-clinical or different stages of clinical development using one or more of these technologies to facilitate paracellular or transcellular transport, and recent data on these studies will be presented.