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.
Iannotti
J P
JP
Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia 19104.
Baradet
T C
TC
Tobin
M
M
Alavi
A
A
Staum
M
M
D000818:Animals; D002645:Chickens; D002921:Cicatrix / Q000517:prevention & control*; D003094:Collagen / Q000037:antagonists & inhibitors*; D005260:Female; D005347:Fibroblasts; D006909:Hydroxyproline / Q000008:administration & dosage* / Q000138:chemical synthesis; D007261:Infusions, Intra-Arterial; D008280:Magnetics; D008863:Microspheres; D051381:Rats; D011919:Rats, Inbred Strains; D012588:Scintillation Counting
D003094:Collagen; D006909:Hydroxyproline