Oral mixed micellar system for peptide delivery

Title : Oral mixed micellar system for peptide delivery

Abstract:

Peptide-based therapeutics, in the current biopharmaceutical market, are majorly available as parenteral formulations. Inherent physicochemical properties of peptides including hydrophilicity, bulky size, enzymatic degradation, and stress-induced denaturation make their delivery challenging. The global quest for the delivery of biomolecules by non-invasive routes like nasal, oral, transdermal, or pulmonary has been ongoing with limited commercial success. When dealing with chronic conditions like osteoporosis, diabetes, etc., patient adherence is critical, emphasizing the need for non-invasive therapy. Salmon calcitonin is a 32 amino acid peptide that is approved by the US FDA for use in postmenopausal osteoporosis (PMO), hypercalcemia, and Paget’s disease, mandating long-term therapy. First part of the project was designed for the development of oral peptide formulation by devising suitable delivery strategies. As a part of pre-formulation, computational tools viz. molecular docking and molecular dynamics simulations were used for the development of a prediction module. A library of excipients was screened along with an in-house synthesized lipomer P-lipid, which was found to exhibit a remarkable dual mechanism to enable chymotrypsin inhibition and intestinal membrane permeation, further demonstrated via ex vivo studies. Preliminary evaluation of P-lipid showcased its surfactant property and thus a lipid-based mixed micellar system was developed. P-lipid-based mixed micelles loaded onto silica carrier enabled oral delivery of salmon calcitonin using enteric-coated capsules. The capsules were evaluated for in vitro pharmacopeial parameters followed by in vivo X-ray imaging which confirmed the jejunal release of the capsule contents. The results obtained in the in vivo pharmacokinetic studies reveal an affirmative perspective of this proof-of-concept platform for oral delivery of peptides.

Audience Take Away Notes:

• The audience will learn how to decrease the time for formulation based on the in-silico approach. Also, they would learn the use of simple, cost-effective systems for peptide delivery as well as its characterization. They would get an insight into various invivo studies undertaken
• The study presented is a multidisciplinary study. The audience can either use the concept for their own research or for guiding their research scholars
• The concepts can be used to expand faculty’s research and teaching. Collaborations could be established if researchers are interested to use our platform
• The study presented does provide a technology amenable for scale up and therefore it could be used not only for the peptide studied but various other peptides with similar physico -chemical properties.
• The use of a novel synthesized lipid will be a new information
• The developed technology is simple, cost-effective, stable and scalable for delivering peptides by oral route

Biography:

Prof. Vandana Patravale is a Professor of Pharmaceutics at the Institute of Chemical Technology, Mumbai, India. Her research interests include the development of nano-carriers with a major emphasis on malaria, cancer, and neurodegenerative disorders; medical device development, nano-diagnostics and nano-vaccines. She has over 200 refereed publications, 2 books, 25 book chapters, 30 granted patents, and 2 trademark registries. She is the Vice President of, the CRS-Indian Chapter. She has completed Indo-Swiss, Indo-Japan, and Indo-UK projects and is a recipient of the Bill Melinda Gates Grant Award, 2015. She has transferred many technologies to industries including drug-eluting stents, which are being marketed in about 65 countries.