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载阿昔洛韦的 PLA/PEG 纳米纤维通过溶液吹纺制备及其控释和抗病毒活性。

Controlled release and antiviral activity of acyclovir-loaded PLA/PEG nanofibers produced by solution blow spinning.

机构信息

Post-Graduation Program in Materials Engineering (PPCEM), Laboratory of Materials and Biosystems (LAMAB), Federal University of Paraíba (UFPB), João Pessoa, PB, 58051-900, Brazil.

Post-Graduation Program in Dentistry, Federal University of Paraíba, João Pessoa, PB 58051-900, Brazil.

出版信息

Biomater Adv. 2022 May;136:212785. doi: 10.1016/j.bioadv.2022.212785. Epub 2022 Apr 3.

Abstract

Herpetic dermatitis and oral recurrent herpes (ORH) are among the most common human infections. Antiviral drugs such as acyclovir (ACV) are used in the standard treatment for ORH. Despite its therapeutic efficacy, ACV is continuously and repetitively administered in high doses. In this sense, the development of controlled release drug delivery systems such as core-shell fibers have a great potential in the treatment of ORH. In this work, poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) fibers were produced by solution blow spinning (SBS) for the controlled release of ACV encapsulated in the core. PLA/PEG nanofibers containing four different blend ratios (100:0, 90:10, 80:20 and 70:30 wt%) without or with 10 wt% ACV were characterized by scanning electron microscopy (SEM), thermogravimetry (TG) and differential scanning calorimetry (DSC). The ACV release profile for 21 days was accessed by UV-Vis spectroscopy. Static water contact angles of the spun fiber mats were measured by the sessile drop method to evaluate fiber wettability upon contact with skin for transdermal release. Cytotoxicity and antiviral efficacy against Herpes simplex viruses (HSV-1) were evaluated using Vero cells. ACV addition did not impact on morphology, but slightly improved thermal stability of the fibers. Addition of hydrophilic PEG in PLA/PEG blends, however, increased drug release as confirmed by contact angle measurements and release profile. The in vitro tests showed the effectiveness of the drug delivery systems developed in reducing HSV-1 viral titer, which is related to the judicious combination of polymers used in the fibrous mats, in addition to not being cytotoxic to Vero cells. These results show the great potential of PLA/PEG solution blow-spun fibers in the controlled release of ACV to develop practical devices for the treatment of cold sores, while favoring the aesthetic appearance by covering them with a soft tissue patch (fibrous mats).

摘要

疱疹性皮炎和口腔复发性疱疹 (ORH) 是最常见的人类感染之一。阿昔洛韦 (ACV) 等抗病毒药物被用于 ORH 的标准治疗。尽管具有治疗功效,但 ACV 仍需持续、重复地以高剂量给药。从这个意义上说,开发控释药物输送系统,如核壳纤维,在 ORH 的治疗中具有很大的潜力。在这项工作中,通过溶液吹纺 (SBS) 生产了聚乳酸/聚乙二醇 (PLA/PEG) 纤维,用于控释包裹在核中的 ACV。通过扫描电子显微镜 (SEM)、热重分析 (TG) 和差示扫描量热法 (DSC) 对含有四种不同共混比 (100:0、90:10、80:20 和 70:30wt%) 的 PLA/PEG 纳米纤维进行了表征,没有或含有 10wt%ACV。通过紫外可见光谱法评估了 21 天的 ACV 释放曲线。通过悬滴法测量纺丝纤维垫的静态水接触角,以评估纤维与皮肤接触时的润湿性,从而实现经皮释放。使用 Vero 细胞评估细胞毒性和抗单纯疱疹病毒 (HSV-1) 的抗病毒功效。ACV 的添加并未影响纤维的形态,但略微提高了纤维的热稳定性。然而,在 PLA/PEG 共混物中添加亲水性 PEG 会增加药物释放,这通过接触角测量和释放曲线得到证实。体外试验表明,所开发的药物输送系统在降低 HSV-1 病毒滴度方面具有有效性,这与用于纤维垫的聚合物的合理组合有关,此外,对 Vero 细胞没有细胞毒性。这些结果表明 PLA/PEG 溶液吹纺纤维在 ACV 的控释方面具有很大的潜力,可开发用于治疗唇疱疹的实用装置,同时通过用软组织贴片 (纤维垫) 覆盖它们来提高美观度。

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