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首页> 外文期刊>Biomaterials Science >Colorectal distribution and retention of polymeric nanoparticles following incorporation into a thermosensitive enema
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Colorectal distribution and retention of polymeric nanoparticles following incorporation into a thermosensitive enema

机译:结合到热敏灌肠后聚合物纳米颗粒的结直肠分布和保留

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Nanotechnology-based systems have been proposed for rectal drug delivery, often rendering promising outcomes concerning disease prophylaxis or therapeutics. However, nanocarriers often feature reduced colorectal retention when administered in liquid vehicles (enemas). Semi-solid platforms may be considered as alternative but usually result in limited local distribution. Thermosensitive enemas undergoing sol-gel transition just below body temperature have been used for abbreviating these issues, but the actual impact on the colorectal distribution and retention of incorporated nanosystems is not clear. We prepared and characterized a potential drug delivery platform by incorporating poly(lactic-co-glycolic acid)-based nanoparticles (170-180 nm mean hydrodynamic diameter) into a poloxamer 407-based thermosensitive enema (NPs-in-thermo). The system featured suitable functional properties for rectal administration such as sol-gel transition temperature of approximately 27-28 degrees C, sol-gel transition time of 1.6 min, and viscosity around 31 and 2100 mPa s at 20 degrees C and 37 degrees C, respectively. NPs-in-thermo presented osmolality and pH values deemed compatible with the colorectal compartment, as well as reduced toxicity to the Caco-2 colorectal cell line. The composite system was also used to incorporate the anti-HIV microbicide model drug dapivirine. In vitro studies showed that dapivirine-loaded NPs-in-thermo was able to provide overall faster drug release as compared to dapivirine directly dispersed into phosphate buffered saline or the thermosensitive enema base. Finally, NPs-in-thermo was tested for distribution and retention in a mouse model by in vivo and ex vivo near infrared imaging. Qualitative and semi-quantitative data indicated that NPs exhibited slower but overall wider distribution and enhanced retention in the distal colon of mice treated intrarectally with NPs-in-thermo, namely when compared to NPs dispersed in liquid phosphate buffered saline. Overall, our data support that thermosensitive enemas may provide suitable platforms for the rectal administration of polymeric NPs, namely in the context of drug delivery.
机译:已经提出了基于纳米技术的系统,用于直肠药物递送,通常是有关疾病预防或治疗剂的有希望的结果。然而,当在液体载体(灌肠)施用时,纳米载体通常具有降低的结肠直肠保留。半固体平台可以被认为是替代的,但通常导致局部分布有限。在体温下方溶液过渡的热敏灌肠已被用于缩写这些问题,但实际对结直肠分布和纳入纳米系统保留的实际影响尚不清楚。我们通过将聚(乳酸二乙醇酸)基于泊洛沙姆407的热敏灌肠(NPS-In-Thermo)掺入泊洛沙姆407的热敏灌肠(NPS-In-Thermo)来制备和表征潜在的药物递送平台。该系统特征在于直肠给药,如溶胶 - 凝胶转变温度为约27-28℃,溶胶 - 凝胶转变时间为1.6分钟,粘度约为31和2100mPa s,如20摄氏度,分别。 NPS-In-Thermo呈现渗透性和与结直肠隔室相容的pH值,以及对Caco-2结肠直肠细胞系的毒性降低。复合体系也用于掺入抗HIV杀虫剂模型药物Dapiviin。在体外研究表明,与直接分散到磷酸盐缓冲盐水或热敏灌肠碱的达佩里宁相比,加载Dapivirine负载的NPS-In-Thermo能够提供更快的药物释放。最后,通过体内和离体近红外成像测试了NPS-In-Thermo以在小鼠模型中进行分布和保留。定性和半定量数据表明,NPS表现出较慢但总体更宽的分布,并且在与NPS-In--Thermo intrarbally治疗的小鼠的远端结肠中增强了保持率,即与分散在液态磷酸盐缓冲盐水中的NPS相比。总的来说,我们的数据支持该热敏灌肠可以为直肠施用聚合物NPS提供合适的平台,即在药物递送的背景下。

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