Voriconazole into PLGA nanoparticles: improving agglomeration and antifungal efficacy.
This study is concerned with preparing PLGA nanoparticles loaded with voriconazole (PNLV), investigating the burst release and agglomeration of PNLV, and also evaluating antifungal efficacy of PNLV compared with voriconazole (VRC). The emulsion-solvent evaporation technique for nanoparticles and tests against fungi were completed. The amount of VRC in PNLV with sodium hexametaphosphate was 2.01+/-0.27%, and burst release of PNLV was reduced by about 33% using 20% ethanol solution (n=3). The mean D(50) of PNLV with or without this salt was 132.8 nm and 6.3 microm, respectively (n=5). In vitro; the fungal numbers treated with PNLV (3.5 mg/ml, equal amount calculated by VRC) and VRC (70 microg/ml) in tubes at the day 7 were 5.74 log(10) and 6.72 log(10), respectively (P<0.05). In vivo; the fungal burden treated with PNLV and VRC in tissue from mice kidneys at day 7 after administration was 0.64 log(10) and 2.61 log(10), respectively (5 mg/kg, P<0.001). The hematoxylin-eosin stain in mice kidney showed that the pathological lesions treated with PNLV were relieved in contrast with those with VRC. These results suggest that the emulsion-solvent evaporation process is feasible in preparing PNLV. Moreover, ethanol solution decreased burst release and Na-HMP inhibited agglomeration. PNLV could improve the VRC antifungal efficacy.
Peng
Hai-sheng
HS
Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, 157 Bao Jian Road, Harbin 150081, China.
Liu
Xi-jun
XJ
Lv
Gui-xiang
GX
Sun
Bo
B
Kong
Qing-fei
QF
Zhai
Dong-xu
DX
Wang
Qi
Q
Zhao
Wei
W
Wang
Guang-you
GY
Wang
Dan-dan
DD
Li
Hu-lun
HL
Jin
Lian-hong
LH
Kostulas
Nikolaos
N
D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D005240:Feasibility Studies; D007668:Kidney / Q000187:drug effects / Q000382:microbiology; D007700:Kinetics; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D010710:Phosphates / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology; D065819:Voriconazole
D000935:Antifungal Agents; D004337:Drug Carriers; D010710:Phosphates; D011743:Pyrimidines; D012997:Solvents; D014230:Triazoles; D011098:Polyglactin 910; D000431:Ethanol; D065819:Voriconazole; C009285:sodium polymetaphosphate