Assessment of hyaluronic acid-conjugated pH-sensitive liposomes for prednisolone delivery to activated macrophages†

Background: inflammatory diseases, including rheumatoid arthritis and osteoarthritis, are major health problems worldwide, often treated with glucocorticoids. These exert anti-inflammatory effects by modulating macrophages and other cells involved in the inflammatory response. While they can be highly effective in managing inflammation, long-term use of glucocorticoids is associated with significant side effects, highlighting the need for targeted strategies and controlled release in specific tissues and cells. We propose the use of hyaluronic acid-conjugated pH-sensitive liposomes to deliver prednisolone (LipoHA:PDP) to activated macrophages. Materials & methods: we evaluated the cytotoxicity and targeting potential of LipoHA:PDP using the THP-1 cell line. Results: LipoHA:PDP significantly inhibited the release of inflammatory mediators and reduced NF-κB translocation to the nucleus. The liposomes also decreased reactive oxygen species (ROS) production. Moreover, LipoHA:PDP prevented albumin denaturation, which impacts immune recognition, inflammation, and tissue damage. Conclusion: LipoHA:PDP was revealed to be a promising nanotherapy to enhance the therapeutic efficacy and efficiency of prednisolone on chronic inflammation long-term treatment.