Local drug delivery is an effective strategy for achieving direct and instant therapeutic effects. Current clinical treatments have fallen short and are limited by traditional technologies. Bioadhesive nanoparticles (NPs), however, may be a promising carrier for optimized local drug delivery, offering prolonged drug retention time and steadily maintained therapeutic concentrations. In addition, the possibility of clinical applications of this platform are abundant, as most polymers used for bioadhesion are both biodegradable and biocompatible. This review highlights the major advances in the investigations of polymer-based bioadhesive nanoparticles and their innumerable applications in local drug delivery.

The effective treatment of esophageal disease represents a significant unmet clinical need, as existing treatments often lead to unnecessary systemic drug exposure and suboptimal concentrations at the disease site. Here, surface-modified bioadhesive poly(lactic acid)-hyperbranched polyglycerol nanoparticles (BNPs), with an average 100–200 nm diameter, were developed for local and sustained esophageal drug delivery. BNPs showed significantly higher adhesion and permeation into ex vivo human and rat esophageal tissue than non-adhesive nanoparticles (NNPs) and had longer residence times within the rat esophagus in vivo. Incubation with human esophagus (Het-1A) cells confirmed BNPs’ biocompatibility at clinically relevant concentrations. In a rat model of achalasia, nifedipine-loaded BNPs significantly enhanced esophageal drug exposure, increased therapeutic efficacy, and reduced systemic drug exposure compared to NNPs and free drug. The safety of BNPs was demonstrated by an absence of intestinal, hepatic, and splenic toxicity following administration. This study is the first to demonstrate the efficacy of BNPs for esophageal drug delivery and highlight their potential for improving the lives of patients suffering with esophageal conditions.