Synergetic effects of doxycycline-loaded chitosan nanoparticles for improving drug delivery and efficacy.
Synergetic effects of doxycycline-loaded chitosan nanoparticles for improving drug delivery and efficacy.
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DOI：
10.2147/ijn.s27328
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发表时间：
2012
影响因子：
8
通讯作者：
Kumar A
中科院分区：
文献类型：
--
作者：
Cover NF;Lai-Yuen S;Parsons AK;Kumar A
强力霉素是一种广谱抗生素，是全世界治疗感染性疾病最常用的抗生素。它可以口服或静脉注射，但可能导致胃肠道刺激和局部炎症。对于子宫感染的治疗，包封在由可生物降解的壳聚糖制成的纳米颗粒中的多西环素的经宫颈给药可以改善药物的持续递送，从而使不良反应最小化并改善药物功效。作为评估这种潜力的第一步，我们使用离子凝胶化方法来合成空白和多西环素负载的壳聚糖纳米颗粒（DCNPs），然后我们根据与临床疗效相关的几个特性对其进行表征：粒度，形状，包封效率，抗菌活性和体外细胞毒性。检查了两种颗粒制剂，其中一种（命名为DCNP6）含有约1.5倍于另一种（DCNP4）的交联剂浓度。这两种制剂产生球形载药纳米颗粒。对于DCNP4，球的尺寸范围为30至220 nm直径，对于DCNP6，球的尺寸范围为200至320 nm直径。DCNP4的平均包封率为53%，DCNP6的平均包封率为56%。在药物释放方面，两种制剂在前4至5小时内显示出突释效应，随后在24小时监测期的剩余时间内缓慢持续释放。对大肠杆菌的体外抗菌活性很高，两种制剂对4小时细菌生长的抑制率均超过90%。DCNPs对正常人卵巢表面上皮细胞的细胞毒性作用明显低于未包封的多西环素。5天后，暴露于未包封抗生素的培养物显示细胞活力降低61%，而暴露于DCNP的培养物显示出低于10%的降低。这些实验室结果表明，DCNPs显示出初步的希望，可能最终用于经宫颈给药，并提高治疗细菌性子宫感染的疗效。
Doxycycline, a broad-spectrum antibiotic, is the most commonly prescribed antibiotic worldwide for treating infectious diseases. It may be delivered orally or intravenously but can lead to gastrointestinal irritation and local inflammation. For treatment of uterine infections, transcervical administration of doxycycline encapsulated in nanoparticles made of biodegradable chitosan may improve sustained delivery of the drug, thereby minimizing adverse effects and improving drug efficacy. As a first step toward assessing this potential, we used an ionic gelation method to synthesize blank and doxycycline-loaded chitosan nanoparticles (DCNPs), which we then characterized in terms of several properties relevant to clinical efficacy: particle size, shape, encapsulation efficiency, antibacterial activity, and in vitro cytotoxicity. Two particle formulations were examined, with one (named DCNP6) containing approximately 1.5 times the crosslinker concentration of the other (DCNP4). The two formulations produced spherically shaped drug-loaded nanoparticles. The spheres ranged in size from 30 to 220 nm diameter for DCNP4 and 200 to 320 nm diameter for DCNP6. Average encapsulation yield was 53% for DCNP4 and 56% for DCNP6. In terms of drug release, both formulations showed a burst effect within the first 4 to 5 hours, followed by a slow, sustained release for the remainder of the 24-hour monitoring period. The in vitro antibacterial activity against Escherichia coli was high, with both formulations achieving more than 90% inhibition of 4-hour bacterial growth. Cytotoxic effects of the DCNPs on normal human ovarian surface epithelial cells were significantly lower than those of unencapsulated doxycycline. After 5 days, cultures exposed to the unencapsulated antibiotic showed a 61% decrease in cell viability, while cultures exposed to the DCNPs exhibited less than a 10% decrease. These laboratory results suggest that DCNPs show preliminary promise for possible eventual use in transcervical drug delivery and improved efficacy in the treatment of bacterial uterine infections.