Amphotericin B Aggregation Inhibition with Novel Nanoparticles Prepared with Poly(ε-caprolactone)/Poly(N,N-dimethylamino-2-ethyl methacrylate) Diblock Copolymer
2011
Shim, Y.H., Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut, Mons, Belgium | Kim, Y.C., Sungkyunkwan University, Suwon, Republic of Korea | Lee, H.J., Gwangju Development Institute, Gwangju, Republic of Korea | Bougard, Francois, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut, Mons, Belgium | Dubois, Philippe, Center for Innovation and Research in Materials and Polymers (CIRMAP), University of Mons-Hainaut, Mons, Belgium | Choi, K.C., Grassland and Forages Research Center, National Institute of Animal Science, RDA, Cheonan, Republic of Korea | Chung, C.W., Pusan National University Yangsan Hospital, Yangsan, Republic of Korea | Kang, D.H., Pusan National University Yangsan Hospital, Yangsan, Republic of Korea | Jeong, Y.I., Pusan National University Yangsan Hospital, Yangsan, Republic of Korea
Diblock copolymers composed of poly(ε-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, AmB-incorporated PCL-b-PDMAEMA nanoparticles were seen to be 10 times less cytotoxic than free AmB (5 ㎍/ml). In addition, an improved antifungal activity of AmB-incorporated 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.
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