Formulation of stabilizer-free, nontoxic PLGA and elastin-PLGA nanoparticle delivery systems.

Affiliation

Stromberg ZR(1), Lisa Phipps M(2), Magurudeniya HD(2), Pedersen CA(3), Rajale T(2), Sheehan CJ(2), Courtney SJ(1), Bradfute SB(4), Hraber P(5), Rush MN(6), Kubicek-Sutherland JZ(7), Martinez JS(8).
Author information:
(1)Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos NM 87545, USA.
(2)Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos NM 87545, USA.
(3)Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos NM 87545, USA; Center for Materials Interfaces in Research and Applications, Northern Arizona University, Flagstaff AZ 86011, USA; Department of Applied Physics and Materials Science, Northern Arizona University, Flagstaff AZ 86011, USA.
(4)Center for Global Health, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque NM 87131, USA.
(5)Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos NM 87545, USA.
(6)Center for Materials Interfaces in Research and Applications, Northern Arizona University, Flagstaff AZ 86011, USA; Department of Applied Physics and Materials Science, Northern Arizona University, Flagstaff AZ 86011, USA.
(7)Physical Chemistry and Applied Spectroscopy, Chemistry Division, Los Alamos National Laboratory, Los Alamos NM 87545, USA. Electronic address: [Email]
(8)Center for Materials Interfaces in Research and Applications, Northern Arizona University, Flagstaff AZ 86011, USA; Department of Applied Physics and Materials Science, Northern Arizona University, Flagstaff AZ 86011, USA. Electronic address: [Email]

Abstract

Biocompatible nanoparticles composed of poly(lactic-co-glycolic acid) (PLGA) are used as drug and vaccine delivery systems because of their tunability in size and sustained release of cargo molecules. While the use of toxic stabilizers such as polyvinyl alcohol (PVA) limit the utility of PLGA, stabilizer-free PLGA nanoparticles are rarely used because they can be challenging to prepare. Here, we developed a tunable, stabilizer-free PLGA nanoparticle formulation capable of encapsulating plasmid DNA and demonstrated the formation of an elastin-like polymer PLGA hybrid nanoparticle with exceptional stability and biocompatibility. A suite of PLGAs were fabricated using solvent evaporation methods and assessed for particle size and stability in water. We find that under physiological conditions (PBS at 37˚C), the most stable PLGA formulation (P4) was found to contain a greater L:G ratio (65:35), lower MW, and carboxyl terminus. Subsequent experiments determined P4 nanoparticles were as stable as those made with PVA, yet significantly less cytotoxic. Variation in particle size was achieved through altering PLGA stoichiometry while maintaining the ability to encapsulate DNA and were modified with elastin-like polymers for increased immune tolerance. Overall, a useful method for tunable, stabilizer-free PLGA nanoparticle formulation was developed for use in drug and vaccine delivery, and immune targeting.