A novel method to achieve polymeric nanoparticles loaded with peptide therapeutics, which display high encapsulation efficiency, low burst release, and long acting sustained release profiles

A novel method to achieve polymeric nanoparticles loaded with peptide therapeutics, which display high encapsulation efficiency, low burst release, and long acting sustained release profiles.

Overview

A major challenge in the field of peptide and protein therapeutics is effective administration and subsequent delivery to the site of action. Due to their high molecular weight and susceptibility to degradation by both enzymes and extreme pH values, peptides and proteins usually display poor absorption across epithelial membranes and exhibit low oral bioavailability. For this reason, peptide therapeutics such as GLP-1 Receptor Agonists (GLP-1 RAs) are typically administered by subcutaneous injection or even IV. In some cases, even upon injection, peptides can be rapidly metabolized and cleared from circulation and therefore require several injections to be administered daily. The ability to reduce the frequency of injections or convert an approved injectable peptide or protein into a non-injected formulation would represent a major advance in treatment. We have developed a novel Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles that improve demonstrate optimized polymeric nanoparticle formulations containing peptide drugs for improved therapeutic treatments that will decrease the frequency of injections, as proven in our for GLP-1 RAs studies.

Market Opportunity

Drug delivery systems have wide applications, particularly in enhancing the stability, bioavailability, and controlled release of protein and peptide drugs, which are often susceptible to enzymatic degradation and rapid clearance from the body. For example, GLP-1 RAs have emerged as a crucial treatment option for managing type 2 diabetes (T2D) and obesity. However, GLP-1 therapies administered via injection face limitations in accessibility due to complex administration routes that require extensive education, as well as challenges with patient compliance, since frequent injections can impact quality of life. The World Health Organization has estimated that 13% of the world’s adult population is obese. With an improved drug delivery system, this life-changing medication could reach more patients, improve adherence, and play a significant role in curbing the global obesity epidemic.

Innovation and Meaningful Advantages

Formulating peptide and protein nanoparticle delivery systems presents many unique challenges that must be addressed. A major barrier to clinical success in peptide and protein nanoparticle delivery systems is the ability to achieve a precisely tailored, sustained release profile of the drug cargo. Equally important, the size, surface charge, and shape of the nanoparticles must be optimized, as these factors impact the biodistribution, targeting, and overall therapeutic efficacy of the drug in vivo. Even when therapeutic performance is achieved, formulations often encounter significant technical challenges, including issues with drug stability, loading efficiency, scale-up feasibility, batch-to-batch consistency, and economic viability, all of which must be addressed to ensure reliable, scalable, and cost-effective production.

Currently, the most common methods for producing polymeric nanoparticles require an initial step of emulsifying a polymer solvent in an aqueous non-solvent. This emulsification step can sometimes be challenging for formulations with peptide and protein drugs, as the high shear rate and oil-water interfaces may damage the active pharmaceutical ingredient structures. Our process is based on precipitation by phase inversion using solvent and non-solvent pairs which are completely miscible, avoiding these key issues associated with emulsification.This results in nanoparticles which spontaneously precipitate after the immersion of a solubilized polymer solution in a non-solvent. Our polymeric nanoparticles loaded with peptide or protein therapeutics,display high encapsulation efficiency, low burst release, and long-acting sustained release profiles. The low burst release achieved through our technology is almost impossible to recreate with nanoparticle encapsulation of peptides which are water soluble. Our methodology has enabled the use of a very low molecular weight PLGA that is extremely difficult to accomplish with conventional methods known in the art of polymeric nanoparticle formulations.

Collaboration Opportunity: We are interested in exploring research collaborations and licensing opportunities.

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