Synthesis of Amphiphilic Amino Poly-Amido-Saccharide and Poly(lactic) Acid Block Copolymers and Fabrication of Paclitaxel-Loaded Mucoadhesive Nanoparticles.
Bioconjug Chem
; 35(9): 1429-1440, 2024 Sep 18.
Article
en En
| MEDLINE
| ID: mdl-39159059
ABSTRACT
Drug delivery to the esophagus through systemic administration remains challenging, as minimal drug reaches the desired target. Local delivery offers the potential for improved efficacy while minimizing off-target toxicities but necessitates bioadhesive properties for mucosal delivery. Herein, we describe the synthesis of two new mucoadhesive amphiphilic copolymers prepared by sequential ring-opening copolymerization or postpolymerization click conjugation. Both strategies yield block copolymers containing a hydrophilic amine-functionalized poly-amido-saccharide and either a hydrophobic alkyl derivatized poly-amido-saccharide or poly(lactic acid), respectively. The latter resulting copolymers readily self-assemble into spherical, ≈200 nm diameter, positively charged mucoadhesive nanoparticles. The NPs entrap ultrahigh levels of paclitaxel via encapsulation of free paclitaxel and paclitaxel conjugated to a biodegradable, biocompatible poly(1,2-glycerol carbonate). Paclitaxel-loaded NPs rapidly enter cells, release paclitaxel, are cytotoxic to esophageal OE33 and OE19 tumor cells in vitro, and, importantly, demonstrate improved mucoadhesion compared to conventional poly(ethylene glycol)-poly(lactic acid) nanoparticles to ex vivo esophageal tissue.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Poliésteres
/
Paclitaxel
/
Nanopartículas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos