Peptides can have exquisite potency and selectivity in treating disease, but suffer from rapid clearance. Microparticle depot formulations, where the peptide is entrapped in a water-insoluble polymer matrix, have beentested for decades to provide sustained therapeutic release for chronic disease. The traditional microparticlestructure has significant limitations, including low therapeutic content (<5 wt%) and inadequate release profiles.Consequently, only 5 microparticle depots have been approved, representing 7% of marketed peptides. Thisapplication seeks to develop a long-acting microparticle depot formulation using the inverse FlashNanoPrecipitation (iFNP) platform being commercialized by Optimeos Life Sciences. iFNP enables the formationof polymer-coated peptide-loaded nanoparticles in a scalable and continuous manner. These nanoparticles arethen clustered together to produce mechanically strong nanocomposite microparticles. The polymer coatingsurrounding each individual nanoparticle allows for much higher peptide loadings and more controlled, sustainedrelease from the final microparticle. The iFNP technology has been validated using a model peptide, liraglutide, with therapeutic efficacydemonstrated in vivo for 1 month. The proposed research will apply the platform to three approved peptides thatcurrently lack long-acting formulations. The three peptides treat chronic disease and possess varying physicalproperties. This proposed study will validate the universality of the platform and guide the selection of a leadcandidate for development: 1) Aim 1: Optimize encapsulation of three therapeutic peptide candidates in microparticle depots with loadings above 30 wt% 2) Aim 2: Develop microparticle depots with sustained release profiles of active peptide over 1 month and 3 months with minimized peptide degradation. The formulation design will build on the rules derived under an NSF STTR grant between Princeton Universityand Optimeos. Peptides tested to date have all been chemically modified to increase circulation time. Thestructure-encapsulation-release relationships identified in this work will advance our knowledge of suitablecandidates for formulation by the platform. Stability studies, using LC-MS analysis, will identify amino acidresidues with particular susceptibility to degradation that would be candidates for peptide modifications duringlead optimization of formulation candidates. Crucially, the proposed work will translate to the sustained deliveryof proteins, an application where no long-acting formulations are currently marketed.
Public Health Relevance Statement: This Phase I SBIR develops long-acting depot formulations of three peptide therapeutics to reduce
injection frequency from daily to monthly or quarterly. The formulation strategy addresses key
limitations in current depot technologies, including low therapeutic loadings, high processing losses, and
inadequate release profiles. This platform technology could be used to improve dosing schedules for a
range of injectable therapeutics for chronic diseases.
Project Terms:
