Ganciclovir-loaded polymer microspheres in rabbit eyes inoculated with human cytomegalovirus.
OBJECTIVE
To test the antiviral effect of ganciclovir released from biodegradable polymer microspheres in rabbit eyes inoculated with human cytomegalovirus (HCMV).


METHODS
Human cytomegalovirus (5 x 10(3) plaque forming unit in 0.1 ml Hank's balanced salt solution) was inoculated 4 days after gas compression vitrectomy. Injected after 2 days was 10 mg of 300- to 500-micron ganciclovir-loaded microspheres (89.77 micrograms ganciclovir/mg) suspended in 0.1 ml of 2% hydroxypropylmethylcellulose. Blank microspheres were injected as control specimens. Vitritis, retinitis, and optic neuritis were graded from 0(+)-4+ for 14 days to separate the early HCMV-induced disease events from later nonspecific host inflammatory responses. Ganciclovir-loaded microspheres also were injected and observed for biodegradation and tissue reaction for 8 weeks.


RESULTS
In eyes injected with ganciclovir-loaded microspheres, vitritis decreased from days 3 to 14, and retinitis and optic neuritis decreased from days 3 to 9. In eyes injected with blank microspheres, vitritis increased from days 3 to 7, retinitis increased from days 3 to 9, and optic neuritis increased from days 3 to 14. Immunofluorescence of HCMV antigens in retinal tissues was shown only in eyes injected with blank microspheres. Histopathologic analysis showed minimal focal disruption of the retinal architecture in eyes injected with ganciclovir-loaded microspheres. Disorganization of the normal retinal architecture was observed in eyes injected with blank microspheres. No adverse tissue reaction was observed clinically and histopathologically in eyes injected with ganciclovir-loaded microspheres after 8 weeks.


CONCLUSIONS
Ten milligrams of 300 to 500 microns ganciclovir-loaded poly(D,L-lactide-co-glycolide) microspheres control the progression of fundus disease in HCMV-inoculated rabbit eyes.
Veloso
A A
AA
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA.
Zhu
Q
Q
Herrero-Vanrell
R
R
Refojo
M F
MF
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D003587:Cytomegalovirus / Q000276:immunology; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005128:Eye Diseases / Q000188:drug therapy / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015774:Ganciclovir / Q000008:administration & dosage*; D006801:Humans; D019344:Lactic Acid; D008297:Male; D008863:Microspheres; D009902:Optic Neuritis / Q000188:drug therapy / Q000473:pathology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011817:Rabbits; D014776:Virus Cultivation; D014822:Vitreous Body / Q000187:drug effects / Q000473:pathology
D000956:Antigens, Viral; D001672:Biocompatible Materials; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015774:Ganciclovir