Sequential Release of Ibuprofen and the Gasotransmitter Hydrogen sulfide using Oxanorbornane‐Based Synthetic Lipids as Carriers

• Published in: ChemPlusChem (Weinheim, Germany) Germany), 2024-12, Vol.89 (12), p.e202400323-n/a
• Main Authors: Kana Veedu, Akshaya, Panthalattu Parambil, Archana, Manheri, Muraleedharan K.
• Format: Article
• Language: English
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - chemistry; Drug Carriers - chemistry; Drug delivery; Gasotransmitter; Gasotransmitters - chemistry; Gasotransmitters - metabolism; Humans; Hydrogen sulfide; Hydrogen Sulfide - chemistry; Ibuprofen - chemistry; Lipids - chemistry; Nanoparticle; Norbornanes - chemistry; NSAID
• ISSN: 2192-6506; 2192-6506
• DOI: 10.1002/cplu.202400323

After understanding the biological signaling roles of hydrogen sulfide and its involvement in various physiological processes, there has been enormous interest in exploring its therapeutic utility in areas such as cancer, inflammation, cardiovascular diseases, etc. There is also growing interest in using suitable H2S donors in combination with other drugs to improve the treatment outcome through the modulation of multiple pathways. The premature release of H2S from small molecule donors and the difficulty in controlling its spatio‐temporal distribution are the major challenges during these efforts. Hence the development of appropriate carriers that can release this gasotransmitter along with the therapeutic entity of interest in a controlled manner has high significance. In this regard, this report presents a novel drug delivery system from oxanorbornane‐based synthetic lipids that carries a H2S‐releasing 1,2‐dithiole‐3‐thione moiety as part of the head group. Nanoaggregates of the resulting conjugate are not only capable of efficiently entrapping a non‐steroidal anti‐inflammatory drug such as ibuprofen, but also release this drug and H2S in a controlled and sequential manner. Oxanorbornane‐based synthetic lipids carrying 1,2‐dithiole‐3‐thione moiety as part of the head group were synthesized and their aggregates were used for the physical entrapment of a NSAID such as ibuprofen. With an impressive capacity to release this drug and hydrogen sulfide in a controlled and sequential manner, these novel drug delivery systems could offer solutions to the adverse effects of long‐term use of NSAIDs.