(184x) Oral Delivery of Protein Therapeutics Using Self-Assembled Zwitterionic Nanoparticles

Routine intra-articular or subcutaneous injections of protein therapeutics are a popular option to treat autoimmune diseases. While these methods of treatment yield higher bioavailability, they usually have low patient compliance. Oral delivery offers the most benefits over other administration methods because of minimized manufacturing cost, improved accessibility to patients, and reduced discomfort [1]. It is noted that the oral route has significant biological and physicochemical challenges such as the presence of proteolytic enzymes, drastic changes in pH, as well as the mucus and the epithelial cell layer [2]. These layers prevent protein therapeutics from entering the bloodstream and greatly decrease the bioavailability when it does. All these barriers have to be overcome to successfully deliver protein therapeutics orally. One approach to protect them is to use polymeric nanocarriers. In addition, studies have shown that zwitterionic materials are a promising solution to delivering protein therapeutics orally, achieving successful penetration of both the mucus and epithelial cell layers [3]. Thus, in the present work we developed self-assembled nano-sized polymersomes based on block copolymers of polycaprolactone (PCL) and a polysulfobetaine (PSB).

The block copolymers were formed through ring opening polymerization (ROP) and reversible addition fragmentation chain transfer polymerization (RAFT). The nanoparticles were prepared using nanoprecipitation technique. Characterization data demonstrated successful synthesis of three samples with varied molecular weights. The hydrophilic weight fraction was kept around 0.35 to achieve polymersome formation, and the length of the block copolymers was varied to analyze its effect on the nanoparticle size and stability. The nanoparticle formation process was optimized until nanoparticles with a desired size (between 50 and 200 nm) and a narrow PDI were obtained. Transmission electron microscope images revealed the presence of sphere-shaped polymersomes. Future studies include analyzing the loading and release of Alexa Fluor 488-tagged Bovine Serum Albumin from the nanoparticles. The potential to cross the mucus and the epithelial cell barrier will be analyzed using Caco-2 and HT-29/MTX co-culture. By applying the material design of self-assembled nanocarriers to deliver proteins orally, the proposed work has the potential to revolutionize treatment strategies for autoimmune diseases.

References:

1. Antosova Z. Trends Biotechnol. 2009;27:628-635.
2. Vela Ramirez JE. Drug Deliv. Rev. 2017;114:116-131.
3. Han X. Nanotechnol. 2020;15:605-614.