Kinetics of a Model Nucleoside (Guanosine) Release from Biodegradable Poly(dl-lactide-co-glycolide) Microspheres: A Delivery System for Long-Term Intraocular Delivery

Abstract

The objective of this study was to prepare poly(dl-lactide-co-glycolide)(PLGA) microspheres containing guanosine as a model drug for intraocular administration. Microspheres were prepared by solvent evaporation technique using o/w emulsion system. The influence of composition and molecular weight of PLGA, drug loading efficiency, microsphere size, and in vitro and in vivo release rates were determined. Differential scanning calorimetry (DSC) and FTIR studies were conducted to examine the guanosine–polymer interaction. In vitro release studies indicated that the permeant release from microspheres exhibits an initial burst followed by slow first-order kinetics. Ascending molecular weights of the polymers generated progressively slower release rates. Three different sizes of microspheres were prepared. The release continued for 7 days with a maximum of 70% of the content released within that time period. DSC and FTIR studies showed no polymer–guanosine interaction. A novel microdialysis technique was used to examine the initial release kinetics from microspheres in isolated vitreous humor. This technique was also employed to observe in vivo intravitreal release in albino rabbits. A good correlation exists between in vitro and in vivo release rates from both 75 and 140 kDa PLGA microspheres. Guanosine-loaded microspheres could be prepared for once-a-week intravitreal injection with minimum required concentration maintained throughout the dosing interval. Because the structural and solubility characteristics of guanosine are similar to those of acyclovir and ganciclovir (two acycloguanosine analogues effective against herpes simplex virus [HSV-1] and cytomegalovirus [CMV], respectively), similar biodegradable polymer-based microsphere technology can be employed for the long-term intraocular delivery of these two drugs.

Keywords:

• In vitro–in vivo correlation
• Microspheres
• Particle size
• Poly(DL-lactide-co-glycolide)
• Release rates
• Vitreous fluid