Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies

Matthew K Miller; Fabiola A Chapa-Villarreal; Heidi F Oldenkamp; Michael G Elder; Abhijeet K Venkataraman; Nicholas A Peppas

doi:10.1016/j.jconrel.2023.07.044

Stimuli-responsive self-assembled polymer nanoparticles for the oral delivery of antibodies

J Control Release. 2023 Sep:361:246-259. doi: 10.1016/j.jconrel.2023.07.044. Epub 2023 Aug 8.

Authors

Matthew K Miller¹, Fabiola A Chapa-Villarreal¹, Heidi F Oldenkamp¹, Michael G Elder¹, Abhijeet K Venkataraman², Nicholas A Peppas³

Affiliations

¹ McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX, USA, 78712.
² Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX, USA, 78712; Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA.
³ McKetta Department of Chemical Engineering, 200 E. Dean Keeton St. Stop C0400, Austin, TX 78712, USA; Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX, USA, 78712; Department of Biomedical Engineering, The University of Texas at Austin, 107 W Dean Keeton Street Stop C0800, Austin, TX 78712, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, 2409 University Ave. Stop A1900, Austin, TX 78712, USA; Department of Pediatrics, Dell Medical School, 1400 Barbara Jordan Blvd., Austin, TX 78723, USA; Department of Surgery and Perioperative Care, Dell Medical School, 1601 Trinity St., Bldg. B, Stop Z0800, Austin, TX 78712, USA. Electronic address: peppas@che.utexas.edu.

PMID: 37524149
DOI: 10.1016/j.jconrel.2023.07.044

Abstract

Currently, commercially available antibody therapies must be delivered via parenteral administration. Oral delivery of antibodies could increase patient compliance and improve quality of life, however there is currently no viable system for delivering antibodies orally. In this work, a self-assembled, pH-responsive nanoparticle delivery system was developed to load and deliver antibodies via the oral route. The nanoparticles were synthesized via nanoprecipitation using the pH-responsive copolymers based on poly(methacrylic acid-co-methyl methacrylate)-block-poly(ethylene glycol). The reversibly hydrophobic nature of this polymer allowed it to function as an antibody delivery system via self-assembly. Characteristics of the polymer, including monomer ratios and molecular weight, as well as parameters of the nanoprecipitation process were optimized using Design of Experiments to achieve nanoparticles with desired size, polydispersity, loading efficiency, and release characteristics. Ultimately, the synthesized and optimized nanoparticles exhibited a hydrodynamic size within a range that avoids premature clearance, a low polydispersity index, and high IgG loading efficiency. In in vitro antibody release studies at physiologically relevant pH values, the nanoparticles exhibit promising release profiles. The nanoparticles presented in this work show potential as oral delivery vehicles for therapeutic antibodies.

Keywords: Antibodies; Design of experiments; Nanoparticles; Oral delivery; Self-assembled materials; Stimuli-responsive materials.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Drug Carriers / chemistry
Drug Delivery Systems
Humans
Hydrogen-Ion Concentration
Micelles
Nanoparticles* / chemistry
Polyethylene Glycols / chemistry
Polymers* / chemistry
Quality of Life

Substances

Polymers
Polyethylene Glycols
Micelles
Drug Carriers