Inflammation-responsive delivery systems for the treatment of chronic inflammatory diseases

Abstract

Graphical abstract Inflammation is the biological response of immune system to protect living organisms from injurious factors. However, excessive and uncontrolled inflammation is implicated in a variety of devastating chronic diseases including atherosclerosis, inflammatory bowel disease (IBD), and rheumatoid arthritis (RA). Improved understanding of inflammatory response has unveiled a rich assortment of anti-inflammatory therapeutics for the treatment and management of relevant chronic diseases. Notwithstanding these successes, clinical outcomes are variable among patients and serious adverse effects are often observed. Moreover, there exist some limitations for clinical anti-inflammatory therapeutics such as aqueous insolubility, low bioavailability, off-target effects, and poor accessibility to subcellular compartments. To address these challenges, the rational design of inflammation-specific drug delivery systems (DDSs) holds significant promise. Moreover, as compared to normal tissues, inflamed tissue-associated pathological milieu (e.g., oxidative stress, acidic pH, and overexpressed enzymes) provides vital biochemical stimuli for triggered delivery of anti-inflammatory agents in a spatiotemporally controlled manner. In this review, we summarize recent advances in the development of anti-inflammatory DDSs with built-in pathological inflammation-specific responsiveness for the treatment of chronic inflammatory diseases.

COVID-19 inflammation and implications in drug delivery

“…In order to deliver the anti-COVID-19 agents, either immunomodulator or not, in a selective and specific manner to the injury site, drug delivery systems can be modified to smartly respond to the specific stimuli of the inflammatory microenvironment by releasing their cargo ( Table 2 ) [ [96] , [97] , [98] , [99] ]. The inflammatory biochemical stimulus can be the low pH, the high level of reactive oxygen species (ROS), or the overexpressed inflammatory enzymes [ 95 , 100 ].…”

Longitudinal flux balance analyses of a patient with Crohn’s disease highlight microbiome metabolic alterations

“…LPSs are produced and secreted by gram-negative bacteria (e.g., Salmonella typhimurium 53 and E. coli 54 ), and can provoke an immune response. LPSs are generally soluble as monomers but they can aggregate into fibrous and highly insoluble lipoproteins and lead to inflammation 55 . It has been reported that the concentration of LPS is increased in the acute phases of the disease compared to relapsing ones 56 .…”

Pathologically triggered in situ aggregation of nanoparticles for inflammation-targeting amplification and therapeutic potentiation

“…As for biological therapeutics, their clinical applications have also been compromised due to low stability and bioavailability, high cost, primary/secondary non-responses, and the increased risk of infections or malignancies 4 , 22 , 23 . Regardless of small molecular agents and biological therapies against inflammatory diseases, their systemic exposure or non-specific biodistribution post oral or parenteral administration is a key issue responsible for their adverse drug reactions 24 , 25 , 26 . Therefore, both new drugs and creative delivery strategies are necessary to achieve more desirable treatment of inflammatory diseases.…”