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用于局部应用和药物持续释放的羟丙基甲基纤维素生物粘附水凝胶：聚乙烯吡咯烷酮对水凝胶物理机械性能的影响

Hydroxypropyl Methylcellulose Bioadhesive Hydrogels for Topical Application and Sustained Drug Release: The Effect of Polyvinylpyrrolidone on the Physicomechanical Properties of Hydrogel.

作者信息

Pan Patrick, Svirskis Darren, Waterhouse Geoffrey I N, Wu Zimei

机构信息

School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand.

School of Chemical Sciences, Faculty of Science, The University of Auckland, Auckland 1142, New Zealand.

出版信息

Pharmaceutics. 2023 Sep 21;15(9):2360. doi: 10.3390/pharmaceutics15092360.

DOI:10.3390/pharmaceutics15092360
PMID:37765328
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10537184/
Abstract

Hydrogels are homogeneous three-dimensional polymeric networks capable of holding large amounts of water and are widely used in topical formulations. Herein, the physicomechanical, rheological, bioadhesive, and drug-release properties of hydrogels containing hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined, and the intermolecular interactions between the polymers were explored. A three-level factorial design was used to form HPMC-PVP binary hydrogels. The physicomechanical properties of the binary hydrogels alongside the homopolymeric HPMC hydrogels were characterized using a texture analyzer. Rheological properties of the gels were studied using a cone and plate rheometer. The bioadhesiveness of selected binary hydrogels was tested on porcine skin. Hydrophilic benzophenone-4 was loaded into both homopolymeric and binary gels, and drug-release profiles were investigated over 24 h at 33 °C. Fourier transform infrared spectroscopy (FTIR) was used to understand the inter-molecular drug-gel interactions. Factorial design analysis supported the dominant role of the HPMC in determining the gel properties, rather than the PVP, with the effect of both polymer concentrations being non-linear. The addition of PVP to the HPMC gels improved adhesiveness without significantly affecting other properties such as hardness, shear-thinning feature, and viscosity, thereby improving bioadhesiveness for sustained skin retention without negatively impacting cosmetic acceptability or ease of use. The release of benzophenone-4 in the HPMC hydrogels followed zero-order kinetics, with benzophenone-4 release being significantly retarded by the presence of PVP, likely due to intermolecular interactions between the drug and the PVP polymer, as confirmed by the FTIR. The HPMC-PVP binary hydrogels demonstrate strong bioadhesiveness resulting from the addition of PVP with desirable shear-thinning properties that allow the formulation to have extended skin-retention times. The developed HPMC-PVP binary hydrogel is a promising sustained-release platform for topical drug delivery.

摘要

水凝胶是能够容纳大量水分的均质三维聚合物网络，广泛应用于局部制剂中。在此，研究了含有羟丙基甲基纤维素（HPMC）和聚乙烯吡咯烷酮（PVP）的水凝胶的物理力学、流变学、生物粘附性和药物释放特性，并探讨了聚合物之间的分子间相互作用。采用三级析因设计来制备HPMC-PVP二元水凝胶。使用质地分析仪对二元水凝胶以及均聚物HPMC水凝胶的物理力学性能进行了表征。使用锥板流变仪研究了凝胶的流变学特性。在猪皮肤上测试了所选二元水凝胶的生物粘附性。将亲水性二苯甲酮-4负载到均聚物凝胶和二元凝胶中，并在33℃下研究了24小时内的药物释放曲线。使用傅里叶变换红外光谱（FTIR）来了解分子间药物-凝胶相互作用。析因设计分析支持HPMC在决定凝胶特性方面起主导作用，而非PVP，两种聚合物浓度的影响均呈非线性。向HPMC凝胶中添加PVP可提高粘附性，而不会显著影响其他特性，如硬度、剪切变稀特性和粘度，从而提高生物粘附性以实现皮肤的持续保留，而不会对化妆品可接受性或易用性产生负面影响。HPMC水凝胶中二苯甲酮-4的释放遵循零级动力学，PVP的存在显著延迟了二苯甲酮-4的释放，这可能是由于药物与PVP聚合物之间的分子间相互作用，FTIR证实了这一点。HPMC-PVP二元水凝胶由于添加了PVP而表现出很强的生物粘附性，并具有理想的剪切变稀特性，这使得制剂具有延长的皮肤保留时间。所开发的HPMC-PVP二元水凝胶是一种很有前途的局部药物递送缓释平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/53adb6b6513f/pharmaceutics-15-02360-g011.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/fd474391cd45/pharmaceutics-15-02360-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/3205973b582e/pharmaceutics-15-02360-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/bfaf1cd99872/pharmaceutics-15-02360-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/ade208e50d7f/pharmaceutics-15-02360-g009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b1a/10537184/53adb6b6513f/pharmaceutics-15-02360-g011.jpg

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