Volatile Acid-Solvent Evaporation (VASE): Molecularly Homogeneous Distribution of Acyclovir in a Bioerodable Polymer Matrix for Long-Term Treatment of Herpes Simplex Virus-1 Infections.
Volatile Acid-Solvent Evaporation (VASE): Molecularly Homogeneous Distribution of Acyclovir in a Bioerodable Polymer Matrix for Long-Term Treatment of Herpes Simplex Virus-1 Infections.
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DOI：
10.1155/2018/6161230
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发表时间：
2018
影响因子：
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通讯作者：
Margulies BJ
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文献类型：
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作者：
Stegman JR;Badin JK;Biles KA;Etienne T;Fartash-Naini S;Gordon AD;Greeley ZW;Harding BW;Mack RJ;Masica D;Nelson AN;Samra AK;Smith SE;Thomas GP;Zack HJ;Brunker TJ;Margulies BJ
对反复发作的单纯疱疹病毒-1和-2（HSV-1和-2）患者的治疗包括每天多次服用抗病毒药物阿昔洛韦（ACV）、喷昔洛韦或其口服生物利用度更高的衍生物伐昔洛韦或泛昔洛韦。漏服剂量引起的药物低谷可能会导致病毒复制，从而产生耐药突变体以及临床后遗症。我们开发了一种 ACV 与可生物侵蚀的聚合物聚己内酯的分子均质混合物。通过扫描电子显微镜、红外光谱、凝胶渗透色谱、1H NMR 和差示扫描量热法，我们将药物和聚合物结合的方法称为挥发性酸溶剂蒸发 (VASE)，不会损害聚合物或药物的完整性。此外，VASE 创造的材料可以在大约两个月内持续输送治疗量的药物。载药量足够高的装置可将 Vero 细胞中 HSV-1 的初次感染降低至与单剂量 ACV 相同的水平。我们的数据将导致在动物模型中进行进一步的实验，证明通过单次干预以及其他适合这种操作的抗病毒药物可以有效防止这些病毒重新激活。此外，这种类型的治疗在其使用寿命后不会留下任何痕迹，因为药物被释放并且聚合物基质在体内降解。
Treatment for herpes simplex virus-1 and -2 (HSV-1 and -2) patients who suffer from recurrent outbreaks consists of multiple daily doses of the antiviral drugs acyclovir (ACV), penciclovir, or their more orally bioavailable derivatives valacyclovir or famciclovir. Drug troughs caused by missed doses may result in viral replication, which can generate drug-resistant mutants along with clinical sequelae. We developed a molecularly homogeneous mixture of ACV with the bioerodable polymer polycaprolactone. Through scanning electron microscopy, infrared spectroscopy, gel permeation chromatography, 1H NMR, and differential scanning calorimetry, our method of combining drug and polymer, termed Volatile Acid-Solvent Evaporation (VASE), does not compromise the integrity of polymer or drug. Furthermore, VASE creates materials that deliver therapeutic amounts of drug consistently for approximately two months. Devices with high enough drug loads diminish primary infection of HSV-1 in Vero cells to the same level as seen with a single dose of ACV. Our data will lead to further experiments in animal models, demonstrating efficacy in preventing reactivation of these viruses with a single intervention, and with other antiviral drugs amenable to such manipulation. Additionally, this type of treatment would leave no trace after its useful lifetime, as drug is released and polymer matrix is degraded in vivo.