Synthesis of Amphiphilic Amino Poly-Amido-Saccharide and Poly(lactic) Acid Block Copolymers and Fabrication of Paclitaxel-Loaded Mucoadhesive Nanoparticles
Year: 2024
Type: article
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.
Source: Bioconjugate Chemistry
Institutions: Boston University, Massachusetts General Hospital
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
Funders: Boston University, Harvard University, Harvard Catalyst, Boston Area Diabetes Endocrinology Research Center, National Institutes of Health, Office of the Director, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Biomedical Imaging and Bioengineering, National Center for Advancing Translational Sciences
Awards: G1589144027, G170437431, G171471675, G1717162763, G2032961523, G2118519186, G2187521452, G2620970834, G2722067147, A Zeiss LSM800 confocal microscope with Airyscan, G3097843832, G4883012012, OPTIMIZATION OF NANOPARTICLE TUMOR-LOCALIZATION AND DRUG-LOADINGFOR TREATING MESOTHELIOMA, G9000011862, G9000018359, G9000065669, G9000080734, G9000115447, G9000146438, G9000175365, Center for the Study of Inflammatory Bowel Disease at Massachusetts General Hospital
OpenAlex ID: W4401693952