Iannotti J P, Baradet T C, Tobin M, Alavi A, Staum M
Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia 19104.
J Orthop Res. 1991 May;9(3):432-44. doi: 10.1002/jor.1100090316.
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.
合成了含有脯氨酸类似物顺式羟基脯氨酸的磁响应性白蛋白微球，并对其体外物理性质进行了表征。这些微球的平均尺寸为1.1±0.3微米，94%的微球小于2.0微米。它们呈均匀的球形，含有67%的白蛋白、22%的磁铁矿和8%的顺式羟基脯氨酸。顺式羟基脯氨酸在72小时内可释放，并显示出一个缓慢的可释放库，约占所掺入药物的50%。顺式羟基脯氨酸在掺入微球的过程中，其化学性质和生物学性质均未改变。微球中顺式羟基脯氨酸的释放导致体外胶原蛋白分泌受到抑制，这与未掺入的顺式羟基脯氨酸无法区分。在大鼠尾部动物模型中，使用施加于1.5 - 2.0厘米靶部位的外部磁场对这些微球进行选择性靶向。注入的微球中有50%至80%定位于该部位，而在没有磁场的情况下，只有15%至20%的微球定位于该部位。与未治疗的动物相比，顺式羟基脯氨酸微球在瘢痕模型中使胶原蛋白含量降低了16%（p < 0.05）。随着这种药物递送方法的进一步完善，可能会在临床上有效抑制瘢痕形成。
