title: Biocompatibility of injectable chitosan-phospholipid implant systems.
abstract: Injectable biomaterials are desirable therapeutic platforms due to minimal invasiveness and improved patient compliance, and are applicable in such areas as compound delivery and tissue engineering. The present work examined the biocompatibility of injectable blends composed of chitosan, phospholipid and lauric aldehyde (PoLi(gel)-LA) or lauric chloride (PoLi(gel)-LCl). In vitro cytotoxicity was evaluated in L929 and HeLa cell lines. Both blends resulted in acceptable biocompatibility, although greater cell viability was seen with PoLi(gel)-LA. In vivo biocompatibility was investigated in healthy CD-1 mice. Subcutaneous injection of the PoLi(gel)-LA blend caused no local or systemic toxicities over a four-week period while the PoLi(gel)-LCl caused immediate local toxicity. Mice injected intraperitoneally with PoLi(gel)-LA did not show physical or behavioural alterations, and body weight changes did not differ from control animals. Furthermore, histological examination of spleen and liver showed unaltered morphology. Interleukin-6 levels in mice injected with PoLi(gel)-LA did not differ from levels of control animals (6.91+/-3.61 pg/mL versus 6.92+/-5.02 pg/mL, respectively). Biodegradation occurred progressively, with 7.4+/-5.02% of the original injected mass remaining after four weeks. Results obtained herein establish the biocompatibility of PoLi(gel)-LA and indicate its potential for use in various localized therapeutic applications.
authors.affiliation: Department of Pharmaceutical Sciences, University of Toronto, 144 College Street, Toronto, Ontario, Canada M5S-3M2.
authors.forename: Raquel
authors.initials: R
authors.lastname: De Souza
authors.forename: Payam
authors.initials: P
authors.lastname: Zahedi
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Allen
authors.forename: Micheline
authors.initials: M
authors.lastname: Piquette-Miller
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000187:drug effects; D051379:Mice; D010743:Phospholipids / Q000737:chemistry*; D013154:Spleen / Q000187:drug effects; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D015850:Interleukin-6; D010743:Phospholipids; D048271:Chitosan