Sustainably derived poly(glycerol adipate) (PGA) delivers all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability [1]. Previously, we have shown as new functionalities can be introduced directly in the one-pot PGA enzymatic polymerisation without the need of further synthetic steps. By introducing 1,6-n-hexanediol (Hex), as hydrophobic diol, we managed to tune the amphiphilic balance of the new repetitive unit with consequent enhanced drug encapsulation [2]. In the present work, we further investigate the effect of amphiphilic balance variation upon physical properties and drug interactions as well as self-assembly and NPs stability. We replaced glycerol with the more hydrophilic diglycerol, and then we adjusted the final amphiphilic balance of the polyester repetitive units by incorporating Hex. The produced materials have been extensively characterised, NPs have been produced and tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo experiments. [1] Swainson SME, Styliari ID, Taresco V, Garnett MC. Poly (glycerol adipate) (PGA), an Enzymatically Synthesized Functionalizable Polyester and Versatile Drug Delivery Carrier: A Literature Update. Polymers (Basel). 2019, 11(10), 1561. [2] P. L. Jacob, L. A. Ruiz Cantu, A. K. Pearce, Y. He, J. C. Lentz, J. C. Moore, F. Machado, G. Rivers, E. Apebende, M. R. Fernandez, I. Francolini, R. Wildman, S. M. Howdle and V. Taresco, Polymer (Guildf)., 2021, 228, 123912.
Tailored Modifications of Poly (glycerol adipate) and Poly (diglycerol adipate) to Improve Drug Encapsulation / Brugnoli, Benedetta; Jacob, Philippa L.; Francolini, Iolanda; Taresco, Vincenzo. - (2023). (Intervento presentato al convegno Petals Winter School tenutosi a Claviere (TO)).
Tailored Modifications of Poly (glycerol adipate) and Poly (diglycerol adipate) to Improve Drug Encapsulation
Benedetta Brugnoli;Iolanda Francolini;Vincenzo Taresco
2023
Abstract
Sustainably derived poly(glycerol adipate) (PGA) delivers all the desirable features expected in a polymeric scaffold for drug-delivery, including biodegradability, biocompatibility, self-assembly into nanoparticles (NPs) and a functionalisable pendant group. Despite showing these advantages over commercial alkyl polyesters, PGA suffers from a series of key drawbacks caused by poor amphiphilic balance. This leads to weak drug-polymer interactions and subsequent low drug-loading in NPs, as well as low NPs stability [1]. Previously, we have shown as new functionalities can be introduced directly in the one-pot PGA enzymatic polymerisation without the need of further synthetic steps. By introducing 1,6-n-hexanediol (Hex), as hydrophobic diol, we managed to tune the amphiphilic balance of the new repetitive unit with consequent enhanced drug encapsulation [2]. In the present work, we further investigate the effect of amphiphilic balance variation upon physical properties and drug interactions as well as self-assembly and NPs stability. We replaced glycerol with the more hydrophilic diglycerol, and then we adjusted the final amphiphilic balance of the polyester repetitive units by incorporating Hex. The produced materials have been extensively characterised, NPs have been produced and tested for their stability in different environments and for their ability to encode enhanced drug loading. Moreover, the novel materials have shown good biocompatibility in both in vitro and in vivo experiments. [1] Swainson SME, Styliari ID, Taresco V, Garnett MC. Poly (glycerol adipate) (PGA), an Enzymatically Synthesized Functionalizable Polyester and Versatile Drug Delivery Carrier: A Literature Update. Polymers (Basel). 2019, 11(10), 1561. [2] P. L. Jacob, L. A. Ruiz Cantu, A. K. Pearce, Y. He, J. C. Lentz, J. C. Moore, F. Machado, G. Rivers, E. Apebende, M. R. Fernandez, I. Francolini, R. Wildman, S. M. Howdle and V. Taresco, Polymer (Guildf)., 2021, 228, 123912.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
