通过全身给药将药物输送到食道仍然具有挑战性，因为到达所需目标的药物最少。局部递送具有提高疗效的潜力，同时最大限度地减少脱靶毒性，但粘膜递送需要生物粘附特性。在此，我们描述了通过顺序开环共聚或后聚合点击共轭制备的两种新型粘膜粘附两亲共聚物的合成。两种策略均产生分别含有亲水性胺官能化聚酰胺糖和疏水性烷基衍生的聚酰胺糖或聚(乳酸)的嵌段共聚物。后者产生的共聚物很容易自组装成球形、直径约 200 nm、带正电的粘膜粘附纳米颗粒。纳米颗粒通过封装游离紫杉醇和与可生物降解、生物相容性聚（1,2-甘油碳酸酯）结合的紫杉醇来捕获超高水平的紫杉醇。负载紫杉醇的纳米粒子快速进入细胞，释放紫杉醇，在体外对食管OE33和OE19肿瘤细胞具有细胞毒性，而且重要的是，与传统的聚（乙二醇）-聚（乳酸）纳米粒子相比，它对离体食管组织的粘膜粘附力有所改善。

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.