TY - JOUR
T1 - Poly (glycerol adipate) (PGA) backbone modifications with a library of functional diols
T2 - Chemical and physical effects
AU - Jacob, Philippa L.
AU - Ruiz Cantu, Laura A.
AU - Pearce, Amanda K.
AU - He, Yinfeng
AU - Lentz, Joachim C.
AU - Moore, Jonathan C.
AU - Machado, Fabricio
AU - Rivers, Geoffrey
AU - Apebende, Edward
AU - Fernandez, Maria Romero
AU - Francolini, Iolanda
AU - Wildman, Ricky
AU - Howdle, Steven M.
AU - Taresco, Vincenzo
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/7/16
Y1 - 2021/7/16
N2 - Enzymatically synthesised poly(glycerol adipate) (PGA) has shown a palette of key desirable properties required for a biomaterial to be considered a ‘versatile polymeric tool’ in the field of drug delivery. PGA and its variations can self-assemble into nanoparticles (NPs) and interact at different levels with small active molecules. PGA derivatives are usually obtained by functionalising the glyceryl side hydroxyl group present along the main polymer scaffold. However, if the synthetic pathways are not finely tuned, the self-assembling ability of these new polymeric modifications might be hampered by the poor amphiphilic balance. For this reason, we have designed a straightforward one-pot synthetic modification, using a small library of diols in combination with glycerol, aimed at altering the backbone of the polymer without affecting the hydrophilic glyceryl portion. The diols introduce additional functionality into the backbone of PGA alongside the secondary hydroxyl group already present. We have investigated how extra functionalities along the polymer backbone alter the final polymer reactivity as well the chemical and biological properties of the nanoparticles. In addition, with the intent to further improve the green credentials of the enzymatic synthesis, a solvent derived from renewable resources, (2-methyl tetrahydrofuran, 2-MeTHF) was employed for the synthesis of all the PGA-variants as a replacement for the more traditionally used and fossil-based tetrahydrofuran (THF). In vitro assays carried out to evaluate the potential of these novel materials for drug delivery applications demonstrated very low cytotoxicity characteristic against NIH 3T3 model cell line.
AB - Enzymatically synthesised poly(glycerol adipate) (PGA) has shown a palette of key desirable properties required for a biomaterial to be considered a ‘versatile polymeric tool’ in the field of drug delivery. PGA and its variations can self-assemble into nanoparticles (NPs) and interact at different levels with small active molecules. PGA derivatives are usually obtained by functionalising the glyceryl side hydroxyl group present along the main polymer scaffold. However, if the synthetic pathways are not finely tuned, the self-assembling ability of these new polymeric modifications might be hampered by the poor amphiphilic balance. For this reason, we have designed a straightforward one-pot synthetic modification, using a small library of diols in combination with glycerol, aimed at altering the backbone of the polymer without affecting the hydrophilic glyceryl portion. The diols introduce additional functionality into the backbone of PGA alongside the secondary hydroxyl group already present. We have investigated how extra functionalities along the polymer backbone alter the final polymer reactivity as well the chemical and biological properties of the nanoparticles. In addition, with the intent to further improve the green credentials of the enzymatic synthesis, a solvent derived from renewable resources, (2-methyl tetrahydrofuran, 2-MeTHF) was employed for the synthesis of all the PGA-variants as a replacement for the more traditionally used and fossil-based tetrahydrofuran (THF). In vitro assays carried out to evaluate the potential of these novel materials for drug delivery applications demonstrated very low cytotoxicity characteristic against NIH 3T3 model cell line.
KW - Enzymatic polymerisation
KW - Polyglycerol adipate (PGA)
KW - Self-assembly
UR - http://www.scopus.com/inward/record.url?scp=85108840691&partnerID=8YFLogxK
U2 - 10.1016/j.polymer.2021.123912
DO - 10.1016/j.polymer.2021.123912
M3 - Article
AN - SCOPUS:85108840691
SN - 0032-3861
VL - 228
JO - Polymer
JF - Polymer
M1 - 123912
ER -