Block copolymer composition drives function of self‐assembled nanoparticles for delivery of small‐molecule cargo

• Published in: Journal of polymer science. Part A, Polymer chemistry Vol. 57; no. 12; pp. 1322 - 1332
• Main Authors: Maikawa, Caitlin L., Sevit, Alex, Lin, Binhong, Wallstrom, Rachel J., Mann, Joseph L., Yu, Anthony C., Waymouth, Robert M., Appel, Eric A.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.06.2019
• Subjects: drug delivery; nanoparticles; polymerization; polymers; polymerization; nanoparticles; drug delivery; polymers
• ISSN: 0887-624X; 1099-0518
• DOI: 10.1002/pola.29393

ABSTRACT Nanoparticles are useful for the delivery of small molecule therapeutics, increasing their solubility, in vivo residence time, and stability. Here, we used organocatalytic ring opening polymerization to produce amphiphilic block copolymers for the formation of nanoparticle drug carriers with enhanced stability, cargo encapsulation, and sustained delivery. These polymers comprised blocks of poly(ethylene glycol) (PEG), poly(valerolactone) (PVL), and poly(lactide) (PLA). Four particle chemistries were examined: (a) PEG‐PLA, (b) PEG‐PVL, (c) a physical mixture of PEG–PLA and PEG–PVL, and (d) PEG–PVL–PLA tri‐block copolymers. Nanoparticle stability was assessed at room temperature (20 °C; pH = 7), physiological temperature (37 °C; pH = 7), in acidic media (37 °C; pH = 2), and with a digestive enzyme (lipase; 37 °C; pH = 7.4). PVL‐based nanoparticles demonstrated the highest level of stability at room temperature, 37 °C and acidic conditions, but were rapidly degraded by lipase. Moreover, PVL‐based nanoparticles demonstrated good cargo encapsulation, but rapid release. In contrast, PLA‐based nanoparticles demonstrated poor stability and encapsulation, but sustained release. The PEG–PVL–PLA nanoparticles exhibited the best combination of stability, encapsulation, and release properties. Our results demonstrate the ability to tune nanoparticle properties by modifying the polymeric architecture and composition. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1322–1332 Nanoparticles (NPs) are useful for the delivery of small molecule therapeutics to increase their solubility, in vivo residence time, and stability. In this work, the authors used organocatalytic ring opening polymerization to produce amphiphilic tri‐block copolymers for the formation of NP drug carriers with enhanced stability, cargo encapsulation, and sustained delivery. PEG–PVL–PLA NPs demonstrated the best combination of properties. The results demonstrate the ability to tune NP properties by modifying the polymeric architecture and composition.