挥发性酸-溶剂蒸发(花瓶):无环鸟苷在生物可腐蚀聚合物基质中的分子均匀分布,用于长期治疗单纯疱疹病毒1型感染。

Journal of drug delivery Pub Date : 2018-09-26 eCollection Date: 2018-01-01 DOI:10.1155/2018/6161230
James R Stegman, Jill K Badin, Kaitlyn A Biles, Thamar Etienne, Sogand Fartash-Naini, Ariel D Gordon, Zachary W Greeley, Benjamin W Harding, Ricardo J Mack, Danielle Masica, Ashley N Nelson, Amandeep K Samra, Sarah E Smith, Gabrielle P Thomas, Haley J Zack, Timothy J Brunker, Barry J Margulies
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引用次数: 4

摘要

对反复发作的单纯疱疹病毒-1和-2 (HSV-1和-2)患者的治疗包括每日多次剂量的抗病毒药物阿昔洛韦(ACV)、喷昔洛韦或其更口服的生物可利用衍生物valacyclovir或famciclovir。错过剂量引起的药物低谷可能导致病毒复制,从而产生耐药突变体并伴随临床后遗症。我们开发了一种分子均匀的ACV与生物可腐蚀聚合物聚己内酯的混合物。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,我们的药物和聚合物结合的方法,称为挥发性酸-溶剂蒸发(花瓶),不损害聚合物或药物的完整性。此外,花瓶创造的材料,提供治疗量的药物持续约两个月。具有足够高药物负荷的装置将Vero细胞中HSV-1的原发感染减少到与单剂量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,证明单次干预在防止这些病毒再激活方面的有效性,以及适用于此类操作的其他抗病毒药物。此外,由于药物释放和聚合物基质在体内降解,这种治疗方法在使用寿命后不会留下任何痕迹。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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.

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.

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.

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Journal of drug delivery
Journal of drug delivery PHARMACOLOGY & PHARMACY-
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