Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Wiesenstrasse 14, 35390 Giessen, Germany.
Institute of Bioprocess Engineering and Pharmaceutical Technology, University of Applied Sciences Mittelhessen, Wiesenstrasse 14, 35390 Giessen, Germany; Faculty of Biology and Chemistry, Justus-Liebig University Giessen, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
Int J Pharm. 2019 May 30;563:208-216. doi: 10.1016/j.ijpharm.2019.04.005. Epub 2019 Apr 3.
Biopharmaceutical development is progressing rapidly. It is imperative that novel drug delivery systems are designed to protect the integrity of the biopharmaceutical, and, at the same time, transport and distribute the drug efficaciously to the target site. Administration of highly specific and sensitive molecules, like therapeutic proteins or nucleic acid-based drugs, present distinct challenges. In this study, we investigate the topical drug delivery of 10-23 DNAzymes; short single-stranded oligonucleotides with RNA-cleaving properties. We developed different hydrogel formulations based on chitosan. These natural-based polymers are particularly suitable for biopharmaceuticals due to their high biocompatibility and biodegradability. We tested these hydrogels for penetration enhancement and for protective efficacy against DNAzymes degradation. Additionally, we examined the physicochemical characteristics and the storage stability of several hydrogel preparations. The formulations developed in this study demonstrate adequate antimicrobial activity, even without the addition of preservatives. A DNAse II degradation assay confirmed their ability to prevent enzymatic degradation of the oligonucleotide. The recovery of intact oligonucleotides in full thickness porcine skin samples indicated that hydrogel formulations composed of DNA/chitosan polyplexes provided satisfactory skin penetration.
生物制药的发展正在迅速推进。当务之急是设计新的药物输送系统，以保护生物制药的完整性，同时有效地将药物输送和分布到靶位。高度特异性和敏感性分子（如治疗性蛋白质或基于核酸的药物）的给药带来了明显的挑战。在这项研究中，我们研究了 10-23 DNA 酶的局部药物输送；这是具有 RNA 切割特性的短单链寡核苷酸。我们基于壳聚糖开发了不同的水凝胶配方。这些天然聚合物由于其高度的生物相容性和生物降解性，特别适合于生物制药。我们测试了这些水凝胶对穿透增强和对 DNA 酶降解的保护效果。此外，我们还检查了几种水凝胶制剂的物理化学特性和储存稳定性。本研究中开发的配方表现出足够的抗菌活性，即使没有添加防腐剂也是如此。DNAse II 降解分析证实了它们防止寡核苷酸酶降解的能力。完整寡核苷酸在全厚猪皮样本中的回收表明，由 DNA/壳聚糖聚电解质复合物组成的水凝胶配方提供了令人满意的皮肤穿透性。
