Cyclodextrin‐Derived Intrinsically Bioactive Nanoparticles for Treatment of Acute and Chronic Inflammatory Diseases

Abstract

Inflammation is a common cause of many acute and chronic inflammatory diseases. A major limitation of existing anti‐inflammatory therapeutics is that they cannot simultaneously regulate pro‐inflammatory cytokine production, oxidative stress, and recruitment of neutrophils and macrophages. To overcome this limitation, nanoparticles (NPs) with multiple pharmacological activities are synthesized, using a chemically modified cyclic oligosaccharide. The manufacture of this type of bioactive, saccharide material‐based NPs (defined as LCD NP) is straightforward, cost‐effective, and scalable. Functionally, LCD NP effectively inhibits inflammatory response, oxidative stress, and cell migration for both neutrophils and macrophages, two major players of inflammation. Therapeutically, LCD NP shows desirable efficacies for the treatment of acute and chronic inflammatory diseases in mouse models of peritonitis, acute lung injury, and atherosclerosis. Mechanistically, the therapeutic benefits of LCD NP are achieved by inhibiting neutrophil‐mediated inflammatory macrophage recruitment and by preventing subsequent pro‐inflammatory events. In addition, LCD NP shows good safety profile in a mouse model. Thus, LCD NP can serve as an effective anti‐inflammatory nanotherapy for the treatment of inflammatory diseases mainly associated with neutrophil and macrophage infiltration.

Bioresponsive drug delivery systems for the treatment of inflammatory diseases

“…In other studies, polymers containing PKCα-specific peptide substrates were designed and prepared for targeted gene delivery [ 269 ], while caspase-3-cleavable polymeric nanocarriers were constructed using a caspase-3 substrate-based peptide linker for intracellular site-specific delivery of caspase-3 [ 270 ]. By covalently conjugating luminol onto cyclic oligosaccharides (such as α-CD and β-CD), MPO-responsive materials can be easily synthesized for imaging and therapy of inflammatory diseases [ 78 , 79 , 271 ]. Whereas enzyme-responsive delivery systems exhibit extremely higher specificity than those responsive to pH or ROS, sensitive peptides are generally required for their preparation, thereby resulting to complicated procedures and high cost in most cases.…”

Nanomedicine-Based Therapeutics to Combat Acute Lung Injury

“…Because nanoparticles can be easily phagocytosed by macrophages, they possess a superior ability to control the inflammatory responses mediated by macrophages. 37,[45][46][47]62,64,67,68,71,73,79 Among the leukocytes at the sites of inflammation, neutrophils are the first to be recruited in response to chemotactic factors. 80 They migrate across the endothelium and through the epithelium into the alveoli, then release histotoxic mediators to damage lung tissue, such as reactive oxygen species (ROS), neutrophil extracellular submit your manuscript | www.dovepress.com…”

“…TPCD nanoparticles eliminated a broad spectrum of ROS, protected macrophages from apoptosis, attenuated inflammatory responses and oxidative stress 47 (Figure 5). In another study, luminol-conjugating β-CD (LCD) nanoparticles could act on both neutrophils and macrophages, effectively inhibiting the inflammatory response, oxidative stress and cell migration, demonstrating desirable efficacy in treating ALI with biosafety 45 (Table 5).…”

“…18 The above characteristics offer targets for site-specific delivery and the microenvironment for responsive drug release. To this end, the nanomedicine for ALI has broad alternative therapeutic strategies, including the delivery of anti-inflammatory agents to the disease site, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] the direct scavenging of inflammatory factors, [35][36][37][38][39][40][41][42][43][44][45][46][47] the regulating of inflammatory cell activities, [48][49][50][51][52][53][54][55][56][57][58][59] or the modulating of inflammatory signaling pathways. [60][61][62][63][64][65]…”

Antioxidant Nanotherapies for the Treatment of Inflammatory Diseases

“…Also, resveratrol-loaded lipidcore nanocapsules (RSV-LNCs) were studied to ameliorate ALI via the ERK and PI3K/Akt pathways (de Oliveira et al, 2019). In addition, intrinsically bioactive nanoparticles derived from functional cyclodextrin materials TPCD and LCD that were developed by our group, were able to accumulate in the injured lungs, suppress oxidative stress, and significantly reduce the infiltration of inflammatory cells in a mouse model of ALI (Figures 3C-H) Guo et al, 2019). Consequently, both inorganic and organic ROS-scavenging nanoparticles can serve as a potent remedy for the treatment of ALI.…”