期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 563, 期 -, 页码 208-216出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2019.04.005
关键词
DNAzyme; 10-23 DNAzyme; Chitosan; Hydrogel; Dermal drug delivery; Penetration studies
资金
- German Federal Ministry of Education and Research [03FH031]
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.
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