title: Biocompatibility and safety evaluation of a ricinoleic acid-based poly(ester-anhydride) copolymer after implantation in rats.
abstract: The aim of this study was to evaluate the safety and tissue compatibility of an injectable biodegradable poly(ester-anhydride) copolymer of ricinoleic acid (RA) and sebacic acid (SA) in rats. The absorbable biomaterial containing 70% w/w of RA and 30% w/w of SA [P(SA-RA) 3:7] was implanted in rats in two separate studies: (1) at high doses subcutaneously (SC) and intramuscularly (IM) simultaneously into the same animal and (2) intracranially (IC). The safety was established in the high-dose administration experiment. No systemic tissue damage, polymer-related lesions, or abnormalities could be detected in the animals. The histopathological evaluation of the SC and IM P(SA-RA) 3:7 implanted sites suggested a typical foreign body reaction (FBR) to biomaterials, and was characterized by excellent tissue repair and good tissue tolerance. In the second experiment, no neurological deficits or behavior changes suggestive of systemic or localized toxicity were observed in the animals implanted IC with the polymer. Only minimal, well-demarcated inflammatory response was observed on days 14 and 21 and consisted of glia cells. No abnormalities were noted in the brain tissue parenchyma located further from the edges of the implant. These results demonstrated that the P(SA-RA) 3:7 copolymer was tolerated well by the animals and compatible with rat subcutaneous, muscle and brain tissues. The biodegradable polymeric system described here could be used as a scaffold for varied applications in localized and sustained delivery of therapeutic agents.
authors.affiliation: Department of Medicinal Chemistry and Natural Products, School of Pharmacy-Faculty of Medicine, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Vaisman
authors.forename: Menachem
authors.initials: M
authors.lastname: Motiei
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Abraham J
authors.initials: AJ
authors.lastname: Domb
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001672:Biocompatible Materials / Q000737:chemistry / Q000633:toxicity*; D001772:Blood Cell Count; D001774:Blood Chemical Analysis; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects; D003652:Decanoic Acids / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D005549:Foreign-Body Reaction / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008422:Materials Testing; D009132:Muscles / Q000033:anatomy & histology / Q000187:drug effects; D009457:Neuroglia / Q000473:pathology; D011108:Polymers / Q000737:chemistry / Q000633:toxicity*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D012277:Ricinoleic Acids / Q000737:chemistry / Q000633:toxicity*; D040521:Subcutaneous Tissue / Q000033:anatomy & histology / Q000187:drug effects
chemical_list: D001672:Biocompatible Materials; D003652:Decanoic Acids; C493322:Poly(sebacic acid-co-ricinoleic acid); D011108:Polymers; D012277:Ricinoleic Acids