Superior performance of chitosan microspheres loaded with hyperbranched polylysine for endotoxin adsorption: From molecular interactions to hemoperfusion applications

  • Carbohydr Polym. 2026 Jun 15:382:125269. doi: 10.1016/j.carbpol.2026.125269.
Yuhui Feng  1 ,  Ziyue Ling  1 ,  Xianda Liu  1 ,  Hongyu Xiang  1 ,  Boyang Liu  1 ,  Weifeng Zhao  2 ,  Changsheng Zhao  3
Affiliations
  • 1. College of Polymer Science and Engineering, State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu, 610065, China.
  • 2. College of Polymer Science and Engineering, State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu, 610065, China. Electronic address: [email protected].
  • 3. College of Polymer Science and Engineering, State Key Laboratory of Advanced Polymer Materials, Sichuan University, Chengdu, 610065, China. Electronic address: [email protected].
PMID: 42002347 DOI: 10.1016/j.carbpol.2026.125269
Abstract

Sepsis triggered by lipopolysaccharide (LPS) is a life-threatening condition. Inspired by the specific capture mechanism of innate proteins like LBP and CD14, we develop oxidized chitosan microspheres functionalized with hyperbranched polylysine (OCS-HBPL) as a Sepsis detoxification agent. Isothermal titration calorimetry (ITC) reveals that HBPL-LPS binding is an enthalpy-driven process, distinct from the entropy-driven interaction of linear polylysine (LPL)-LPS. Validated by surface plasmon resonance (SPR), HBPL demonstrates superior affinity with a dissociation constant (KD) of 2.44 × 10-6 M, being 3.8-fold lower than that of LPL. Although both Polymers show similar saturation adsorption capacities by quartz crystal microbalance with dissipation (QCM-D), HBPL exhibits significantly superior erythrocyte compatibility compared to LPL. The OCS-HBPL microspheres achieved a remarkable 73.6% LPS clearance ratio in simulated whole-blood hemoperfusion. Simultaneously, their bovine serum albumin (BSA) adsorption was restricted to 34 μg/g, only 10% of the OCS-LPL control. Crucially, the OCS-HBPL microspheres exhibit a negligible hemolysis ratio, standing in sharp contrast to the unsafe levels (>2%) observed in OCS-LPL. These results demonstrate that HBPL endows chitosan microspheres with both high LPS clearance capacity and excellent hemocompatibility. Thus, OCS-HBPL microspheres show great potential applications in Sepsis treatment and open new routes in the development of biocompatible polysaccharide Materials.

Keywords
Chitosan; Endotoxin; Hyperbranched Polylysine; Lipopolysaccharide; Sepsis.
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