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Table 3 A summary of nanocarrier-assisted delivery of immunomodulators for potential management of infectious diseases and the associated complications

From: Nanocarriers for effective delivery: modulation of innate immunity for the management of infections and the associated complications

Nanocarrier

Target site / Type

Load

Formulation

Model

Role

Potential Application

Refs.

Liposome

TLR7/8

Resiquimod

Hydrogenated (soy) L-a-phosphatidylcholine, 1,2-distearoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DOPG), cholesterol and D-a-tocopherol

Murine

Immunomodulatory drug

Visceral L. donovani infection

[224]

TLR3, TLR9

Poly I:C and noncoding plasmid DNA (pDNA)

Cationic liposome; 1,2-dioleoyl-3-trimethylammonium propane

Kitten

Immunomodulatory drug

Feline herpesvirus-1 infection

[225]

TLR3, TLR9

Poly I:C and pDNA

LTC; Cationic lipid 1,2-dioleoyl- 3-trimentylammonium-propane (DOTAP) and cholesterol

Cat

Immunomodulatory drug

Bacterial respiratory tract infections in cat

[227]

TLR3, TLR9

Poly I:C and pDNA

LTC; cationic lipid DOTAP and cholesterol

Dog

Immunomodulatory drug

Viral and bacterial infections in dog

[228]

TLR1/2, TLR9

Pam3CysSK4 (PMA) and CpGs

DOTAP and cholesterol

Mice

Vaccine adjuvant

/

[232]

STING

cdGMP

PEGlyated liposome; 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), DOPG, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), DSPE-PEG

Mice

Vaccine adjuvant

HIV-1

[271]

STING

cGAMP

Pulmonary surfactant-biomimetic liposomes; 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC), 1,2-dipalmitoyl-sn- glycero-3-phospho-(1'-rac-glycerol) (DPPG), DPPE-PEG, cholesterol

Mice and ferrets

Vaccine adjuvant

H1N1

[244]

IDR

Nisin Z

Phosphatidylcholine (PC), PC-cholesterol, and PC–phosphatidylglycerol (PG)–cholesterol

In vitro

Immunomodulatory drug

Listeria monocytogenes

[247]

IDR

Polymyxin B

DPPC and cholesterol or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol

In vitro

Immunomodulatory drug

Gram negative bacterial strains

[249]

IDR

LL-37

1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), DSPE-mPEG2000 and cholesterol

3D epidermis model

Immunomodulatory drug

HSV

[250]

Polymersome

TLR8

CL075 (a synthetic imidazoquinoline)

Poly (ethylene glycol)-bl-poly(propylene sulfide) (PEG-bl-PPS)

Neonatal mice

Vaccine adjuvant

Vaccine delivery system for human neonatal vaccines against infections e.g. Mycobacterium tuberculosis

[236]

Micelle

STING

cGAMP

PEG-b-PR copolymer

Clinical

Vaccine adjuvant

Avian and swine influenza

[242]

IDR

DP7-C

A modified DP7 (an active IDR) with cholesterol to form an amphiphilic conjugate

Zebrafish and mice

Immunomodulatory drug

Bacterial infection

[252]

Lipid nanoparticle

TLR7

mRNA

An ionizable lipid, a phospholipid, a sterol, and a lipid-anchored PEG

Clinical

Vaccine adjuvant

SARS-CoV-2

[235]

Polymeric nanoparticle

TLR4; TLR1/2; TLR9; NOD2

LPS; PAM; CpG DNA, MDP

N-trimethyl chitosan (TMC) nanoparticles

Mice

Vaccine adjuvant

/

[233]

TLR, macrophage polarization

siERN1

Nanoparticles synthesized using folic acid, PEG, PEI, PBAA, a cell-penetrating peptide

Mice

Immunomodulatory drug

Collagen-induced arthritis and LPS-induced over-inflammation

[230]

TLR

/

PLGA, PLA nanoparticles

Mice

Inherent immunomodulatory effect of nanoparticles

Sepsis

[231]

TLR4, TLR7

MPL, R837

PLGA nanoparticles

Mice, rhesus macaque

Vaccine adjuvant

H1N1

[234]

NOD1, NOD2

CL235 [tetradecanoyl-δ-D-glutamyl-L)-meso- lanthionyl-(D)-alanine]…, CL365 [6-O-stearoyl-N-glycolyl-Murabutide]…

Poly(Lactic Acid) (PLA) nanoparticle coating with HIV-1 Gag p24 antigen

Mice

Vaccine adjuvant

Safe and efficient vaccine for infectious diseases

[237]

NOD1

iE-DAP

Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanoparticle

In vitro

Vaccine adjuvant

Potential for being used in the defense against infections

[238]

NOD2 and TLR4 agonists

monophosphoryl lipid A, muramyl dipeptide

PLGA nanoparticle

Mice

Vaccine adjuvant

Influenza infection

[239]

Immunostimulation of macrophage

Amphotericin B

PLGA nanoparticle

In vitro

Immunomodulatory drug

Visceral leishmaniasis

[258]

Immunostimulation of macrophage

Rifampicin

PLGA nanoparticle

In vitro

Immunomodulatory drug

anti-tubercular

[259]

Immunostimulation of macrophage

Curcumin

Mannosylated chitosan nanoparticle

Rat

Immunomodulatory drug

Visceral leishmaniasis

[262]

Immunostimulation of macrophage

AHP

PEI-modified PLGA nanoparticles

Mice

Immunomodulatory drug

H5N1

[268]

Macrophage polarization

ITA

Polyester polymer-ITA biomimetic material

Mice

Immunomodulatory drug

Resolve infection-associated over-inflammation

[269]

Metallic nanoparticles

IDR

Esculentin-1a(1–21)NH2

AuNPs

In vitro

Immunomodulatory drug

P. aeruginosa

[253]

IDR

Cecropin-melittin

AuNPs

Mice

Immunomodulatory drug

Sepsis

[254]

IDR

Nisin

AuNPs

In vitro

Immunomodulatory drug

Multi-drug resistance and non-multi-drug resistant Staphylococcus aureus and Enterococcus faecalis

[255]

Dendrimer

TLR4

Glucosamine

Polypropyletherimine dendrimer

Rhesus macaques

Immunomodulatory drug

Cytokine storm in severe bacterial diarrhea

[229]