[Delivery of macromolecular drugs to the vitreous and its peripheral tissues].
We evaluated the release behavior of FITC-dextran with an average molecular weight of 4,400(FD4), as a model peptide drug, from poly(DL-lactic acid) (PLA) implant. The drug level in the vitreous and its peripheral tissues were measured following the implantation in the rabbit vitreous. The release profile of FD4 from the PLA implant was biphasic; a fraction of the drug molecules incorporated in the polymer implant was swiftly released; then slowly or even negligibly for a certain period of time and finally complete bursting release probably due to bulk erosion of the polymer. The time-course of drug concentration in the vitreous and aqueous humor after implantation showed a constant level for 14 days and then parabola, where the highest concentration appeared around 28 days. The drug concentrations in the retina/ choroid was maintained a constant level for 28 days. After an injection of FD4 in the rabbit vitreous, the drug concentration in those tissues approximately decreased mono-exponentially. These findings suggest that the present implant could be a useful carrier for delivery of macromolecular drugs to the vitreous and its peripheral tissues.
Morita
Y
Y
Kobe Creative Center, Senju Pharmaceutical Co., Ltd.
Saino
H
H
Tojo
K
K
D000818:Animals; D002829:Choroid / Q000378:metabolism; D003911:Dextrans / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015918:Infusion Pumps, Implantable; D046911:Macromolecular Substances; D008970:Molecular Weight; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism*
D003911:Dextrans; D046911:Macromolecular Substances; C015219:fluorescein isothiocyanate dextran; D016650:Fluorescein-5-isothiocyanate