title: In vitro and in vivo evaluation of biodegradable embolic microspheres with tunable anticancer drug release.
abstract: Natural polymer-derived materials have attracted increasing interest in the biomedical field. Polysaccharides have obvious advantages over other polymers employed for biomedical applications due to their exceptional biocompatibility and biodegradability. None of the spherical embolic agents used clinically is biodegradable. In the current study, microspheres prepared from chitosan and carboxymethyl cellulose (CMC) were investigated as a biodegradable embolic agent for arterial embolization applications. Aside from the enzymatic degradability of chitosan units, the cross-linking bonds in the matrix, Schiff bases, are susceptible to hydrolytic cleavage in aqueous conditions, which would overcome the possible shortage of enzymes inside the arteries. The size distribution, morphology, water retention capacity and degradability of the microspheres were found to be affected by the modification degree of CMC. An anticancer drug, doxorubicin, was successfully incorporated into these microspheres for local release and thus for killing cancerous cells. These microspheres demonstrated controllable degradation time, variable swelling and tunable drug release profiles. Co-culture with human umbilical vein endothelial cells revealed non-cytotoxic nature of these microspheres compared to monolayer control (P>0.95). In addition, a preliminary study on the in vivo degradation of the microspheres (100-300μm) was performed in a rabbit renal embolization model, which demonstrated that the microspheres were compatible with microcatheters for delivery, capable of occluding the arteries, and biodegradable inside arteries. These microspheres with biodegradability would be promising for embolization therapies.
authors: Department of Radiology, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Lihui
authors: L
authors: Weng
authors: Parinaz
authors: P
authors: Rostamzadeh
authors: Navid
authors: N
authors: Nooryshokry
authors: Hung C
authors: HC
authors: Le
authors: Jafar
authors: J
authors: Golzarian
mesh_terms: D020341:Absorbable Implants; D000327:Adsorption; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D001783:Blood Flow Velocity / Q000187:drug effects; D002214:Capsules / Q000008:administration & dosage / Q000138:chemical synthesis*; D002478:Cells, Cultured; D002480:Cellulase / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D016461:Chemoembolization, Therapeutic / Q000379:methods; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D004058:Diffusion; D004343:Drug Implants / Q000008:administration & dosage / Q000138:chemical synthesis*; D042783:Endothelial Cells / Q000187:drug effects; D006490:Hemostatics / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D006801:Humans; D007269:Injections, Intra-Arterial; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D004343:Drug Implants; D006490:Hemostatics; D048271:Chitosan; D002480:Cellulase; C019826:carboxymethylcellulase