Inhibitory efficacy of intravitreal dexamethasone acetate-loaded PLGA nanoparticles on choroidal neovascularization in a laser-induced rat model.
OBJECTIVE
The aims of this study were to investigate the inhibitory efficacy of intravitreal dexamethasone acetate (DA)-loaded by (D, L-lactide-co-glycolide) (PLGA) nanoparticles on choroidal neovascularization (CNV) in a laser-induced rat model and to evaluate its mode of drug release.


METHODS
DA loaded with PLGA nanoparticles containing 50% DA was prepared using an emulsification/solvent evaporation method. CNV was unilaterally induced by laser photocoagulation in rats. Different dosages of sterilized DA-loaded PLGA nanoparticles suspensions by intravitreal injection were evaluated (i.e., 50, 100, 200, and 400 mug) and the blank PLGA vehicle was the control. The concentration of DA in vitreous was measured by reverse-phase high-performance liquid chromatography (RP-HPLC). Flash electroretinography and transmission electron microscopy were performed to assess retinal toxicity. Fluorescein fundus angiography was performed to evaluate the incidence of CNV on days 14 and 56. The animals were sacrificed on day 56, then eyecups were processed for histologic analysis.


RESULTS
The in vitro release of DA from nanoparticles showed that 50% of the drug was released over 2 weeks and controlled release in a linear pattern for 40 days. The pharmacokinetics of DA-loaded PLGA nanoparticles in the eyes with CNV demonstrated a triphasic pattern. The DA concentrations in vitreous remained within the effective range, which is capable of inhibiting inflammatory responses for more than 56 days. On day 14 after photocoagulation, the incidence of CNV was 47.4% as for 50 microg, 28.2% for 100 microg, 15.8% for 200 microg and 7.9% for the 400 microg DA-loaded PLGA nanoparticles group, respectively, and 65.8% for the control. On day 56, The inhibition of DA-loaded PLGA nanoparticles on CNV showed a dose-dependent effect. No sign of retinal toxicity was detected.


CONCLUSIONS
These results suggest that DA-loaded PLGA nanoparticles can dose-dependently inhibit the development of experimental CNV. The controlled intraocular delivery system of DA-loaded PLGA nanoparticles may be a potentiality for CNV treatment.
Xu
Jianfeng
J
Department of Ophthalmology, Institute of Ophthalmology of Chinese PLA, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Wang
Yusheng
Y
Li
Yue
Y
Yang
Xiumei
X
Zhang
Peng
P
Hou
Huiyuan
H
Shi
Yuanyuan
Y
Song
Chunxian
C
D000818:Animals; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003692:Delayed-Action Preparations; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004596:Electroretinography / Q000379:methods; D006016:Glycolates / Q000008:administration & dosage / Q000737:chemistry*; D007267:Injections; D019344:Lactic Acid; D017075:Laser Coagulation / Q000009:adverse effects; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors; D014822:Vitreous Body / Q000737:chemistry
D003692:Delayed-Action Preparations; D006016:Glycolates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D003907:Dexamethasone; C018038:dexamethasone acetate