Delivery systems for incorporation of specialized pro-resolving mediators

The acute process of inflammation triggers the production of specialized pro-resolving mediators (SPMs), which is a resolutive class of oxylipins that actively orchestrate the resolution phase of the inflammatory process and contribute to regaining tissue homeostasis. There is important evidence of SPMs' pharmacological effects in animal models exhibiting a long-lasting analgesic effect by modulating the activation of sensory neurons and immune cells. Additionally, SPM treatment has also shown to be effective in combating bacterial or viral infections, which characterizes these compounds as potent immunoresolvents. However, despite their promising pharmacological potential, those molecules are rapidly metabolized into non-effective subproducts. Furthermore, the effective dose for SPMs to activate their target receptors varies from picogram to nanogram, so larger bolus doses do not increase their biological effect but are rather metabolized and inactivated. SPMs are also thermolabile, which is a challenge in the proposed therapeutic use of them. Thus, in the last 15 years, there has been a growing number of studies proposing the incorporation of SPMs in drug delivery systems (DDS) as a strategy to prolong their biological effects, overcome their quick inactivation and preserve their structures at less extreme temperatures. In this way, this review compiled all published studies involving the use of DDS for SPMs delivery. Our discussion highlights the type of delivery systems, their physical-chemical proprieties, and the observed outcomes in different therapeutic purposes.