title: Hematotoxicological analysis of surface-modified and -unmodified chitosan nanoparticles.
abstract: The increasing interest in using chitosan nanoparticles for controlled drug delivery is hampered by its blood incompatibility, especially for intravenous applications. This study investigated the effects of processing solvents (acetic acid/lactic acid), dispersing media (acidic medium/saline), and surface modifiers (polyethylene glycol, polyvinyl alcohol, and ethylenediaminetetraacetatic acid) on the hemocompatibility of chitosan. Blood compatibility of chitosan nanoparticles prepared by ionotropic gelation with altered surface chemistry was evaluated by assessing their hemolytic activity, platelet aggregation, coagulation, and cytokine induction. It was observed that nanoparticles prepared in lactic acid and dispersed in saline did not show hemolysis, platelet aggregation, or coagulation, whereas nanoparticles prepared in acetic acid showed strong hemolysis. Surface modifiers were not observed to significantly affect blood compatibility, with the exception of EDTA, which delayed blood clotting times. Thus, chitosan nanoparticles prepared in lactic acid and dispersed in saline may be an ideal nanocarrier for parenteral applications.
authors.affiliation: Amrita Centre for Nanosciences & Molecular Medicine, Amrita Institute of Medical Sciences & Research Centre, Amrita Vishwa Vidyapeetham, Kochi 682041, Kerala, India.
authors.forename: Ragima
authors.initials: R
authors.lastname: Nadesh
authors.forename: Dhanya
authors.initials: D
authors.lastname: Narayanan
authors.forename: Sreerekha
authors.initials: S
authors.lastname: P R
authors.forename: Sajini
authors.initials: S
authors.lastname: Vadakumpully
authors.forename: Ullas
authors.initials: U
authors.lastname: Mony
authors.forename: Manzoor
authors.initials: M
authors.lastname: Koyakkutty
authors.forename: Shantikumar V
authors.initials: SV
authors.lastname: Nair
authors.forename: Deepthy
authors.initials: D
authors.lastname: Menon
mesh_terms: D000328:Adult; D001672:Biocompatible Materials / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry* / Q000633:toxicity*; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008422:Materials Testing / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity* / Q000648:ultrastructure; D010314:Partial Thromboplastin Time; D010316:Particle Size; D010974:Platelet Aggregation / Q000187:drug effects; D011517:Prothrombin Time; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013499:Surface Properties; D013818:Thermogravimetry; D055815:Young Adult
chemical_list: D001672:Biocompatible Materials; D016207:Cytokines; D048271:Chitosan
keywords: acetic acid; blood compatibility; chitosan nanoparticles; lactic acid; surface modifiers