[A pharmacodynamics study of an intravitreal amphotericin B drug delivery system for the treatment of experimental Aspergillus fumigatus endophthalmitis].
OBJECTIVE
To observe a new amphotericin B drug delivery system (AmB-DDS), and investigate the therapeutic effects of AmB-DDS on an experimental Aspergillus fumigatus endophthalmitis.


METHODS
(1) In order to observe the effects of AmB-DDS, thirty-four New Zealand albino rabbits were intravitreal injected Aspergillus fumigatus suspension (10(3) colony forming unit, CFU) in applanation of vitreous body before therapy 48 hours. All models were randomly divided into five groups. Group A was the empty control group, treated nothing after Aspergillus fumigatus injection, group B was the empty DDS implantation combined with vitrectomy, no treatment after DDS implanted, group C: AmB 5 microg-injection combined with vitrectomy, the injection was repeated two week later, group D: 250 microg AmB-DDS intravitreal implantation combined with vitrectomy, Group E: 500 microg AmB-DDS intravitreal implantation combined with vitrectomy. Aqueous flare, cells, anterior vitreous cells and vitreous opacity were graded, and vitreous humor smear and culture were performed at different time points after operation in 8 weeks. Two months after operation, light microscopy was used histology evaluation. (2) To observe the release of AmB-DDS in Group H (6 eyes), 500 microg AmB-DDS were implanted in the eye of the rabbits after vitrectomy, vitreous humor was aspirated and the concentrations of amphotericin B were determined by high performance liquid chromatography (HPLC).


RESULTS
The inflammation response was lower in groups C, D, E than groups A, B. There was no significant statistical difference between group A and group B (P > 0.05), but differences among C, D, E and groups A, B were significant (P < or = 0.005). The inflammation grade was lower in group E than group C (P < or = 0.005). There was significant statistical difference between the cure effect of group E and group D (chi(2) = 10.494, P = 0.003). All of vitreous humor smears was positive in 1.5 months after surgery, but the culture was only positive in group A, and B. Pathological examination indicated that normal structure was disappeared in the eyes with Aspergillus endophthalmitis. At the first day after surgery, AmB were observed by analysis of HPLC, there was sustained AmB release in the group of AmB-DDS application during the observation periods.


CONCLUSIONS
The degradable AmB-DDS can effectively suppress the inflammation of the rabbit model of Aspergillus fumigatus endophthalmitis. As an alternative to the current routine therapy, it can be used for the treatment of Aspergillus fumigatus endophthalmitis.
Yang
Xia
X
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China.
Dong
Xiao-Guang
XG
Liu
Ai-Ming
AM
Sun
Shi-Ying
SY
Xie
Li-Xin
LX
Wang
Shen-Guo
SG
D000666:Amphotericin B / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D001232:Aspergillus fumigatus; D016503:Drug Delivery Systems; D009877:Endophthalmitis / Q000188:drug therapy* / Q000382:microbiology; D011817:Rabbits
D000935:Antifungal Agents; D000666:Amphotericin B