Long-term sustained release of ganciclovir from biodegradable scleral implant for the treatment of cytomegalovirus retinitis.
The previous scleral implant composed of poly(D, L-lactide-co-glycolide) with ganciclovir (GCV) had some disadvantages such as the second burst in the late phase of release. In this study, the GCV release rate from scleral implants was modified by blending poly(D,L-lactide) (PLA) of two different molecular weights. The scleral implants were prepared by blending PLA-70000 (molecular weight: 70000) and PLA-5000 (molecular weight: 5000) or PLA-130000 (molecular weight: 130000) and PLA-5000 at weight ratios of 100/0, 95/5, 90/10, 80/20, and 0/100. In vitro release tests were performed in 0.1 M phosphate-buffered solution (pH 7.4) at 37 degrees C. An increase in the blended amount of PLA-5000 clearly accelerated the GCV release and the onset of the second burst in the late phase of release tended to delay. The two implants both prepared at a blend ratio of 80/20 successfully prevented the second burst and the GCV release profiles followed the pseudozero-order kinetics after the initial burst as resulting from a diffusional mechanism following Higuchi's equation. Duration of the sustained GCV release could be controlled by changing the blending ratio of high and low molecular weight PLA. The 25% GCV-loaded scleral implants composed of PLA-70000 and PLA-5000 with a blending ratio of 80/20 were implanted in pigmented rabbit eyes. The GCV concentrations in the vitreous after implantation of PLA-70000/PLA-5000 scleral implant with a blending ratio of 80/20 were maintained in the range of effective level for 6 months without a significant burst. Our results suggest that the blended implants are promising for the intraocular controlled drug delivery over a period of several months to one year to treat cytomegalovirus retinitis.
Kunou
N
N
Department of Ophthalmology, Nagoya City University Medical School, Mizuho-ku, 467-0001, Nagoya, Japan. kuno@iwa.att.ne.jp
Ogura
Y
Y
Yasukawa
T
T
Kimura
H
H
Miyamoto
H
H
Honda
Y
Y
Ikada
Y
Y
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy*; D003692:Delayed-Action Preparations; D004343:Drug Implants; D015774:Ganciclovir / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D011817:Rabbits; D014822:Vitreous Body / Q000378:metabolism
D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D004343:Drug Implants; D015774:Ganciclovir