title: Amphotericin B aggregation inhibition with novel nanoparticles prepared with poly(epsilon-caprolactone)/poly(n,n-dimethylamino-2-ethyl methacrylate) diblock copolymer.
abstract: Diblock copolymers composed of poly(epsilon-caprolactone) (PCL) and poly(N,N-dimethylamino-2-ethyl methacrylate) (PDMAEMA), or methoxy polyethylene glycol(PEG), were synthesized via a combination of ring-opening polymerization and atom-transfer radical polymerization in order to prepare polymeric nanoparticles as an antifungal drug carrier. Amphotericin B (AmB), a natural antibiotic, was incorporated into the polymeric nanoparticles. The physical properties of AmB-incorporated polymeric nanoparticles with PCL-b-PDMAEMA and PCL-b-PEG were studied in relation to morphology and particle size. In the aggregation state study, AmB-incorporated PCL-b- PDMAEMA nanoparticles exhibited a monomeric state pattern of free AmB, whereas AmB-incorporated PCL-b- PEG nanoparticles displayed an aggregated pattern. In in vitro hemolysis tests with human red blood cells, AmBincorporated PCL-b-PDMAEMA nanoparticles were seen to be 10 times less cytotoxic than free AmB (5 microgram/ml). In addition, an improved antifungal activity of AmBincorporated polymeric nanoparticles was observed through antifungal activity tests using Candida albicans, whereas polymeric nanoparticles themselves were seen not to affect activity. Finally, in vitro AmB release studies were conducted, proving the potential of AmB-incorporated PCL-b-PDMAEMA nanoparticles as a new formulation candidate for AmB.
authors.affiliation: Laboratory of Polymeric and Composite Materials, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut, Place du Parc 20, Mons, 7000, Belgium, Korea-Europe Technology Center, Seoul 158-072, Korea.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Shim
authors.forename: You-Chan
authors.initials: YC
authors.lastname: Kim
authors.forename: Hong-Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Francois
authors.initials: F
authors.lastname: Bougard
authors.forename: Philippe
authors.initials: P
authors.lastname: Dubois
authors.forename: Ki-Choon
authors.initials: KC
authors.lastname: Choi
authors.forename: Chung-Wook
authors.initials: CW
authors.lastname: Chung
authors.forename: Dae Hwan
authors.initials: DH
authors.lastname: Kang
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Jeong
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry; D011091:Polyesters / Q000138:chemical synthesis* / Q000737:chemistry; D058105:Polymerization; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D008689:Methacrylates; D009757:Nylons; D011091:Polyesters; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); C016240:polycaprolactone; D000666:Amphotericin B