A freeze-dried fibrin disc as a biodegradable drug release matrix

Abstract

A fibrin clot loaded with soluble tetracycline (TET) was prepared and lyophilized to make discs of a size and shape to use as a drug delivery matrix. On subcutaneous implantation of these discs in mice, they were found to have degraded in 15 days as evidenced by gross and histological examination. The in vitro discharge kinetics of tetracycline from the disc into phosphate buffered saline (PBS) and human serum were compared. It was observed that the release rate of tetracycline from the matrix into serum remained steady from day 1 to day 12, maintaining sufficient concentration that may be required to control microbial growth in the medium. Two different concentrations of fibrinogen were used to fabricate discs denoted as FG200 and FG100, and in both cases the retention rate was comparable when the study medium was serum. In contrast, when suspended in PBS instead of serum, the delivery of the drug into the medium was found to be high for up to the 3rd day when a sharp decline in discharge was observed. The fibrinogen used is a factor that determines not only the longevity of discharge but also fibrinolysis. The degradation of the disc in vitro was visible when the discs were suspended in the buffer, and correspondingly fibrin degradation product (FDP) measured in the medium using an antibody-based assay system was high. Fibrin disc is haemostatic and biodegradable in vivo, and in vitro release of a small molecule at a controlled rate is demonstrated here. Hence, it may be a suitable candidate as a drug delivery implant for short-term use.