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通过酰胺基锚定壳聚糖/聚乙二醇纳米粒实现吉西他滨的位点特异性/靶向递送:对肺癌治疗干预的深入理解。

Site specific/targeted delivery of gemcitabine through anisamide anchored chitosan/poly ethylene glycol nanoparticles: an improved understanding of lung cancer therapeutic intervention.

机构信息

Drug Delivery Research Group, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.

出版信息

Eur J Pharm Sci. 2012 Dec 18;47(5):1006-14. doi: 10.1016/j.ejps.2012.09.012. Epub 2012 Oct 4.

Abstract

Gemcitabine (2', 2'-difluorodeoxycytidine) is a deoxycytidine analog with significant antitumor activity against variety of cancers including non-small cell lung cancer. However, rapid metabolism and shorter half-life of drug mandate higher dose and frequent dosing schedule which subsequently results into higher toxicity. Therefore, there is a need to design a vector which can reduce the burden of frequent dosing and higher toxicity associated with the use of gemcitabine. In this study, we investigated the possibility of improving the targeting potential by employing the surface modification on Chitosan/poly(ethylene glycol) (CTS/PEG) Nanoparticles. We demonstrate formulation and characterization of chitosan/poly(ethylene glycol)-anisamide (CTS/PEG-AA) and compared its efficiency with CTS/PEG and free gemcitabine. Our results reveal its sizeable compatibility, comparatively less organ toxicity and higher antitumor activity in vitro as well as in vivo. This wealth of information surfaces the potential of CTS/PEG-AA nanoparticles as a potent carrier for drug delivery. In brief, this novel carrier opens new avenues for drug delivery which better meets the needs of anticancer research.

摘要

盐酸吉西他滨(2',2'-二氟脱氧胞苷)是一种脱氧胞苷类似物,对多种癌症具有显著的抗肿瘤活性,包括非小细胞肺癌。然而,药物的快速代谢和较短的半衰期要求更高的剂量和更频繁的给药方案,从而导致更高的毒性。因此,需要设计一种载体,以减轻与使用盐酸吉西他滨相关的频繁给药和更高毒性的负担。在这项研究中,我们研究了通过对壳聚糖/聚乙二醇(CTS/PEG)纳米粒子进行表面修饰来提高靶向潜力的可能性。我们设计并表征了壳聚糖/聚乙二醇-茴香酰胺(CTS/PEG-AA),并将其与 CTS/PEG 和游离盐酸吉西他滨进行了比较。我们的结果表明,它具有相当大的相容性、相对较少的器官毒性和更高的体外和体内抗肿瘤活性。这些丰富的信息表明 CTS/PEG-AA 纳米粒子作为一种有效的药物载体具有潜力。简而言之,这种新型载体为药物输送开辟了新途径,更好地满足了抗癌研究的需求。

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