Synthesis and characterization of magnetically responsive albumin microspheres containing cis-hydroxyproline for scar inhibition.

Magnetically responsive albumin microspheres containing the proline analog, cis-hydroxyproline, were synthesized and their in-vitro physical properties were characterized. These microspheres have an average size of 1.1 +/- 0.3 microns with 94% of the microspheres less than 2.0 microns. They are uniformly spherical and contain 67% albumin, 22% magnetite, and 8% cis-hydroxyproline. The cis-hydroxyproline is releasable during a 72-h period and demonstrates a slow, releasable pool that constitutes approximately 50% of the incorporated drug. cis-Hydroxyproline is neither chemically nor biologically altered during its incorporation into the microsphere. cis-Hydroxyproline release from microspheres results in the in vitro inhibition of collagen secretion, which is indistinguishable from unincorporated cis-hydroxyproline. In a rat-tail animal model these microspheres were selectively targeted using an external magnetic field applied to a 1.5-2.0-cm target site. Fifty to 80% of the infused microspheres were localized to this site, whereas without a magnetic field only 15-20% of the microspheres are localized to this site. cis-Hydroxyproline microspheres resulted in a 16% decrease in collagen content in a scar model when compared with untreated animals (p less than 0.05). With further refinement of this method of drug delivery, clinically useful inhibition of scar formation may result.