Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

Area of Science:

• Nanomedicine and Drug Delivery
• Immunotoxicology
• Biomaterials Science

Background:

• Chitosan nanoparticles (NPs) are widely used in drug delivery, but their immunotoxic effects are often overlooked.
• Physicochemical properties of chitosan, such as deacetylation degree (DDA) and molecular weight (MW), alongside endotoxin contamination and control testing, significantly impact immunotoxicity outcomes.
• Limited reporting on these critical factors in scientific literature hinders accurate assessment of chitosan-based NP safety.

Purpose of the Study:

• To investigate the immunotoxicity of chitosan nanoparticles (Chit NPs) prepared with varying DDAs and MWs.
• To compare the immunotoxicity of Chit NPs with their parent chitosan polymers.
• To identify how DDA and NP characteristics influence in vitro immunotoxicity.

Main Methods:

• Chitosan nanoparticles (Chit NPs) were synthesized using ionic gelation of chitosan with sodium tripolyphosphate (TPP).
• Two types of NPs were produced: Chit 80% NPs (80% DDA) and Chit 93% NPs (93% DDA).
• In vitro immunotoxicity was assessed using human peripheral blood monocytes (PBMCs) and the RAW 264.7 cell line, evaluating cell viability, reactive oxygen species (ROS) production, coagulation interference, platelet aggregation, and nitric oxide (NO) production.

Main Results:

• Chit NPs demonstrated greater cytotoxicity than their corresponding chitosan polymers across tested cell lines.
• Chit 80% NPs exhibited higher cytotoxicity in PBMCs, increased ROS in RAW 264.7 cells, and interfered with coagulation compared to Chit 93% NPs.
• Chit 93% NPs induced platelet aggregation, while neither NPs nor polymers caused hemolysis or stimulated TNF-α and IL-6 secretion from PBMCs.

Conclusions:

• The deacetylation degree (DDA) of chitosan and the characteristics of chitosan nanoparticles significantly influence in vitro immunotoxicity.
• Chitosan nanoparticles are generally more cytotoxic than their parent polymers.
• Caution is advised when extrapolating findings from chitosan polymers to nanoparticles and when comparing different chitosan-based delivery systems due to variations in DDA and NP properties.