Preparation and evaluation of sustained release infliximab microspheres

A sustained release microsphere system for an antibody (infliximab, molecular weight: 140 Kd) was formulated with PLGA 50:50 co-polymer using two methods of preparation: phase separation technique and double emulsion technique. Microspheres were made in triplicate using each technique and varying drug-to-polymer ratios. Drug-to-polymer ratio was maintained at 1:5, 1:10, or 1:20. In vitro release profile of infliximab was studied in phosphate-buffered saline solution at 37 °C. The release profile and encapsulation efficiency was compared between the two methods of preparation. The releases data was modeled by the sum of squares method to isolate the dominant release mechanism. The physical attributes of the microspheres prepared were characterized. The biochemical characteristics of infliximab before and after encapsulation were also evaluated by several analytical techniques such as size exclusion chromatography, isoelectric focusing, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biological activity of infliximab was also evaluated before and after encapsulation. The phase separation technique showed much higher entrapment efficiency than the double emulsion technique. Microspheres prepared using the double emulsion technique showed a longer release profile (∼5 days) compared to microspheres prepared using the phase separation technique (∼72 h). Physical and biochemical properties of infliximab did not change significantly after encapsulation into microspheres with either methods of preparation. Microspheres prepared using phase separation showed some loss in bioactivity. Based on this research it can be concluded that the microspheres can present an alternative delivery method for infliximab.

A sustained release microsphere system for an antibody (infliximab, molecular weight: 140 Kd) was formulated using polymers. This antibody is currently in the market for rheumatoid arthritis among various indications. Microspheres were made in triplicate using two techniques and varying drug-to-polymer ratios. Drug-to-polymer ratio was maintained at 1:5, 1:10, or 1:20. The release of drug from microsphere was studied. Biochemical properties of microspheres were also studied before and after encapsulation in microspheres. Various analytical techniques were used to study the biochemical properties of infliximab to ensure that it would be efficacious and safe after encapsulation. Sustained release of drug was observed from the microspheres. Infliximab showed no change in biochemical properties and also showed bioactivity. Based on this research it can be concluded that the microspheres can present an alternative delivery method for infliximab that is safe and efficacious and my result in cost savings for patients.