Design of an Inflammation-Sensitive Polyelectrolyte-Based Topical Drug Delivery System for Arthritis

详细信息    查看全文

• 作者：Divya Bijukumar ; Yahya E. Choonara ; Karmani Murugan…
• 关键词：KEY WORDSalginate ; chitosan ; dodecyl ; l ; pyroglutamate ; drug delivery ; hyaluronan ; inflammation ; topical
• 刊名：AAPS PharmSciTech
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：17
• 期：5
• 页码：1075-1085
• 全文大小：1,922 KB
• 刊物主题：Pharmacology/Toxicology; Biotechnology; Biochemistry, general; Pharmacy;
• 出版者：Springer US
• ISSN：1530-9932
• 卷排序：17

文摘

The most successful treatment strategy for arthritis is intra-articular injections that are costly and have reduced patient compliance. The purpose of the current study was to develop an inflammation-sensitive system for topical drug administration. Multi-macromolecular alginate-hyaluronic acid-chitosan (A-H-C) polyelectrolyte complex nanoparticles, loaded with indomethacin were developed employing pre-gel and post-gel techniques in the presence of dodecyl-l-pyroglutamate (DLP). In addition to in vitro studies, in silico simulations were performed to affirm and associate the molecular interactions inherent to the formulation of core all-natural multi-component biopolymeric architectures composed of an anionic (alginate), a cationic (chitosan), and an amphi-ionic polyelectrolytic (hyaluronic acid) macromolecule. The results demonstrated that DLP significantly influenced the size of the synthesized nanoparticles. Drug-content analysis revealed higher encapsulation efficiency (77.3%) in the presence of DLP, irrespective of the techniques used. Moreover, in vitro drug release studies showed that indomethacin release from the nanosystem was significantly improved (98%) in Fenton’s reagent. Drug permeation across a cellulose membrane using a Franz diffusion cell system showed an initial surge flux (0.125 mg/cm−2/h), followed by sustained release of indomethacin for the post-gel nanoparticles revealing its effective skin permeation efficiency. In conclusion, the study presents novel nanoparticles which could effectively encapsulate and deliver hydrophobic drugs to the target site, particularly for arthritis.