The Potential of Drug Delivery Nanosystems for Sepsis Treatment

Figures & data

Figure 1 The preparation schema of S-thanatin-modifed liposomes loaded with levofloxacin. Reprinted with permission from Fan X, Fan J, Wang X, Wu P, Wu G. S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model. Front Pharmacol. 2015;6:249.²⁵

Figure 2 The treatment schema of 2D Transition Metal Dichalcogenide (TMD) Nanosheets. Reprinted with permission from Yim D, Lee DE, So Y, et al. Sustainable nanosheet antioxidants for sepsis therapy via scavenging intracellular reactive oxygen and nitrogen species. ACS Nano. 2020;14(8):10324–10336. Copyright (2020) American Chemical Society.³⁵

Table 1 The Drug Delivery Nanosystems Developed for Sepsis Therapy

Mechanism	Drug Delivery Nanosystems	Active Compounds	Results	References
Antibacterial	Polycaprolactone nanoparticles	Moxifloxacin and rutin	Demonstrated a good antimicrobial activity against E. coli	[^Citation50]
	S-thanatin functionalized liposomes	Levofloxacin	Significantly enhanced the bacterial internalization, resulting in the synergistic effect of antibiotic and anti-bacterial peptide	[^Citation25]
	Chitosan-mastoparan nanoconstruct	Mastoparan	Exerted lower MIC90 (4 μg/mL), reduced bacterial colony count, and had a synergistic bactericidal effect against MDR clinical A. baumannii isolates.	[^Citation51]
	Anti-mouse ICAM-1 antibody modified pH/enzyme-sensitive nanoparticles	Ciprofloxacin and an (2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide	Effectively eliminated the invasive bacteria and alleviated the inflammatory reaction, thus improving the survival rate.	[^Citation31]
	Vitamin lipid nanoparticles	Antimicrobial peptide and cathepsin B mRNA	Effectively reduced the number of drug-resistant bacteria in the body, and improved the host’s body function.	[^Citation32]
	Spherical, prolate ellipsoidal and oblate PLGA nanoparticles coated with red blood cell membrane	_	Had a lower systemic elimination rate, longer half-life, and stronger bacterial toxins detoxification ability.	[^Citation33]
	Graphene-oxides-based drug delivery nanosystems	_	Exterted strong bacterial killing ability	[^Citation34]
	Two-color gold and multilayer magnetic nanoparticles with giant amplifications of PA and PT contrasts were functionalized with an antibody cocktail for molecular targeting	_	Integrated in vivo multiplex targeting, magnetic enrichment, signal amplification, multicolor recognition, and feedback control	[^Citation52,^Citation53]
Anti-oxidative	WS2, MoSe2, and WSe2 nanosheets	_	Effectively removed ROS and RNS, improved severe sepsis mice survival rate.	[^Citation35]
	Ceria nanoparticles	Atorvastatin	Reduced hepatic damage and systemic swelling.	[^Citation40,^Citation41]
Anti-inflammatory	Doxorubicin linked to BSA via pH-sensitive bonds	Doxorubicin	Targeted the activated neutrophils and showed responsive release behavior of doxorubicin to promote apoptosis of neutrophils.	[^Citation43]
	Solid lipid nanoparticles	Curcumin	Significantly reduced the inflammatory cytokines, reduced organ damage, inhibited the TLR-4, TLR-2, NF-κB in lymph nodes.	[^Citation44]
	Silicium dioxide	Antibiotic	Considerably increased animals` survival rate and intensity of inflammatory system reaction.	[^Citation54]
	Chitosan-coated curcumin nanocrystals	Curcumin	Up-regulated levels of Nrf2, SOD and GST, down-regulated NF-κB, leading to reduced cytokine secretion.	[^Citation55]
Others	MSN-PEI 25K, MSN-PEI 800, and MSN-NH2	_	MSN-PEI 25K with high charge density had a stronger nucleic acid binding ability, stronger inhibitory effect on cfDNA-induced inflammatory response.	[^Citation45]
	Deacetylated poly-N-Acetyl Glucosamine Nanoparticles	miR-126	Nearly 67% of the sepsis mice survived at day 7	[^Citation49]
	Amorphous aluminum hydroxyphosphate nanoparticles	_	Elicited long-lasting and enhanced humoral immunity, and provided protection in S. aureus sepsis mice models.	[^Citation56]

Abbreviations: MIC90, minimal inhibitory concentration; MDR, multidrug-resistant; ICAM-1, intercellular adhesion molecule; PLGA, poly lactic-co-glycolic acid; PA, pulmonary atresia; PT, prothrombin time; WS2, tungsten disulfide; MoSe2, molybdenum selenide; WSe2, tungsten diselenide; ROS, reactive oxygen species; RNS, reactive nitrogen species; BSA, bovine serum albumin; TLR-2, toll-like receptor-2; TLR-4, toll-like receptor-4; TLR-9, toll-like receptor-9; NF kappa B, nuclear factor kappa beta; Nrf2, nuclear factor erythroid-2-related factor 2; SOD, superoxide dismutase; cfDNA, circulating free DNA; MSN, mesoporous silica nanoparticles; PEI, polyethyleneimine.

Table 2 Commercial Nanoformulations for Sepsis Treatment

Name	Company	Nanocomposition	Application	Clinical Stage	Ref.
Abelcet	Enzon Pharmaceutical (Sigma-Tau Pharmaceuticals)	Liposomal amphotericin B	Fungal infection	Commercially available	[^Citation64]
AmBisome	Gilead Sciences	Liposomal amphotericin B	Fungal infection	Commercially available	[^Citation65,^Citation66]
Amphotec	Sequus Pharmaceuticals	Liposomal amphotericin B	Fungal infection	Commercially available	[^Citation64]
Fungisome	Lifecare Innovations	Liposomal amphotericin B	Fungal infection	Commercially available	[^Citation67
Neulasta	Amgen Inc.	Filgrastim-bound polymeric NPs	Fibrile neutropenia	Commercially available	[^Citation68,^Citation69]
LogiCath AgTive	Smiths Medical International	Nanosilver	Antimicrobial coating device	Commercially available	[^Citation70]
PerOssal	Aap Impantate	Calcium sulfate and nanoparticulate hydroxyapatite Composite	Antibiotic delivery	Commercially available	[^Citation71]
Spi-Argent	Spire Biomedical Corporation	Nanosilver	Antimicrobial coating device	Commercially available	[^Citation72^–^Citation74]
TAK-242	Takeda Global Research & Development Center, Inc.	Resatorvid emulsion	Sepsis	Commercially available	[^Citation75^–^Citation77]
PEV7	Pevion Biotech Ltd	r-SAP2 virosomal vaccine	Recurrent vulvovaginal candidiasis	Commercially available	[^Citation78,^Citation79]
Cytosorb	CytoSorbents Corporation	Polymeric nanobeads	Hemoadsorption device for septic shock	Commercially available	[^Citation80^–^Citation84]
MAT2501	Matinas Biopharm	Amikacin-loaded lipid nanocrystals	Bacterial infection	Commercially available	[^Citation85]

Note: Adapted from Papafilippou L, Claxton A, Dark P, Kostarelos K, Hadjidemetriou M. Nanotools for sepsis diagnosis and treatment. Adv Healthc Mater. 2021; 10(1):e2001378. © 2020 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH⁵⁷.

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