Mai, Yang;
Ouyang, Yaqi;
Qin, Yujia;
Jia, Changchang;
McCoubrey, Laura E;
Basit, Abdul W;
Nie, Yichu;
... Liu, Yang; + view all
(2022)
Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure.
Nanoscale
, 14
(23)
pp. 8418-8428.
10.1039/d2nr01846b.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Poly(lactic acid)-hyperbranched polyglycerol nanoparticles enhance bioadhesive treatment of esophageal disease and reduce systemic drug exposure |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1039/d2nr01846b |
| Publisher version: | https://doi.org/10.1039/D2NR01846B |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher's terms and conditions. |
| Keywords: | Local drug delivery; co-polymer synthesis; surface-modified nanoparticles; oesophageal disease; chronic disease treatment; formulation optimization |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10151760 |
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