TY - JOUR
T1 - Formulation of stabilizer-free, nontoxic PLGA and elastin-PLGA nanoparticle delivery systems
AU - Stromberg, Zachary R.
AU - Lisa Phipps, M.
AU - Magurudeniya, Harsha D.
AU - Pedersen, Christine A.
AU - Rajale, Trideep
AU - Sheehan, Chris J.
AU - Courtney, Samantha J.
AU - Bradfute, Steven B.
AU - Hraber, Peter
AU - Rush, Matthew N.
AU - Kubicek-Sutherland, Jessica Z.
AU - Martinez, Jennifer S.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/3/15
Y1 - 2021/3/15
N2 - 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.
AB - 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.
KW - Delivery system
KW - Elastin like polymer (ELP)
KW - Intrinsically disordered protein
KW - Nanoparticle
KW - Poly(lactic-co-glycolic acid) (PLGA)
KW - Polyvinyl alcohol(PVA)
KW - Vaccine
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UR - http://www.scopus.com/inward/citedby.url?scp=85100994397&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2021.120340
DO - 10.1016/j.ijpharm.2021.120340
M3 - Article
C2 - 33545284
AN - SCOPUS:85100994397
SN - 0378-5173
VL - 597
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
M1 - 120340
ER -