Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin
Positively charged polyethylenimines enhance nasal absorption of the negatively charged drug, low molecular weight heparin
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DOI：
10.1016/j.jconrel.2006.08.015
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发表时间：
2006-10-27
影响因子：
10.8
通讯作者：
Ahsan, Fakhrul
中科院分区：
文献类型：
--
作者：
Yang, Tianzhi;Hussain, Alamdar;Ahsan, Fakhrul
本研究检验了带正电荷的聚乙烯亚胺（PEI）通过减少药物分子的负表面电荷来增强低分子量肝素（LMWE）的鼻吸收的假设。PEI和LMVM之间的物理相互作用进行了研究，通过傅里叶变换红外光谱（FTIR），粒度分析，电导率测量，zeta电位分析，和天青A测定。通过将用PEI配制的LMWH施用到麻醉大鼠的鼻中并通过测量血浆抗因子Xa活性来监测药物吸收，研究PEI在增强LMWH的鼻吸收中的功效。通过在大鼠鼻粘膜匀浆中孵育药物来评价LMWH的代谢稳定性。与单独的LMWH或PEI相比，LMWH-PEI制剂的FUR光谱显示峰位置的位移。如天青A测定所揭示的，PEI-LMWH制剂中的电导率、ζ电位和游离LMWH的量的降低表明PEI可能中和LMWH的负表面电荷。PEI在增强经鼻施用的LMWH的生物利用度方面的功效可以排序为PEI-1000 kDa >= PEI-750 kDa > PEI-25 kDa。当PEI-1000 kDa以0.25%的浓度使用时，与对照制剂相比，LMWH的绝对和相对生物利用度均增加了4倍。总之，这些结果表明，聚乙烯亚胺可用作经鼻给药的LMWH的潜在载体。(c)2006 Elsevier B. V.保留所有权利。
This study tests the hypothesis that positively charged polyethylenimines (PEIs) enhance nasal absorption of low molecular weight heparin (LMWE) by reducing the negative surface charge of the drug molecule. Physical interactions between PEIs and LMVM were studied by Fourier transform infrared (FTIR) spectroscopy, particle size analysis, conductivity measurements, zeta potential analysis, and azure A assay. The efficacy of PEIs in enhancing nasal absorption of LMWH was studied by administering LMWH formulated with PEI into the nose of anesthetized rats and monitoring drug absorption by measuring plasma anti-factor Xa activity. The metabolic stability of LMWH was evaluated by incubating the drug in rat nasal mucosal homogenates. FUR spectra of the LMWH-PEI formulation showed a shift in peak position compared to LMWH or PEI alone. Decreases in conductivity, zeta potential and the amount of free LMWH in the PEI-LMWH formulation, as revealed by azure A assay, suggest that PEIs possibly neutralize the negative surface charge of LMWH. The efficacy of PEI in enhancing the bioavailability of nasally administered LMWH can be ranked as PEI-1000 kDa >= PEI-750 kDa > PEI-25 kDa. When PEI-1000 kDa was used at a concentration of 0.25%, there was a 4-fold increase in both the absolute and relative bioavailabilities of LMWH compared to the control formulation. Overall, these results indicate that polyethylenimines can be used as potential carriers for nasally administered LMWHs. (c) 2006 Elsevier B.V. All rights reserved.