TY - JOUR
T1 - Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles
AU - Chen, Ying Chen
AU - Su, Chia Yu
AU - Jhan, Hua Jun
AU - Ho, Hsiu O.
AU - Sheu, Ming Thau
N1 - Publisher Copyright:
© 2015 Chen et al.
PY - 2015/12/2
Y1 - 2015/12/2
N2 - To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic®, Kolliphor®, d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone®, the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone® did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.
AB - To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic®, Kolliphor®, d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone®, the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone® did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.
KW - Amphiphilic polymer
KW - Amphotericin B
KW - DSPE-PEG
KW - Lecithin
KW - Micelle
UR - http://www.scopus.com/inward/record.url?scp=84949816900&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84949816900&partnerID=8YFLogxK
U2 - 10.2147/IJN.S95194
DO - 10.2147/IJN.S95194
M3 - Article
C2 - 26664117
AN - SCOPUS:84949816900
SN - 1176-9114
VL - 10
SP - 7265
EP - 7274
JO - International Journal of Nanomedicine
JF - International Journal of Nanomedicine
ER -