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Table 3 Relevant studies focusing on nanoparticle-based therapy for COPD

From: Novel drug delivery systems targeting oxidative stress in chronic obstructive pulmonary disease: a review

Type

Nanocarrier composition

Drug

Method of preparation

size

Route of administration

Mode of action

Ref

Solid lipid nanoparticle

Lipid and surfactant

Proanthocyanidins

Melt-emulsion method

243 nm

H441 cells

Reduce ROS production

[109]

Lipid

Carvacrol

Fusion-emulsification method

78.72 nm

Inhalation

Minimize the inhalation injury by reducing malondialdehyde and minimize the histological change

[110]

Inorganic nanoparticles

Gold nanoparticles

Au

–

21 nm

Inhalation

AuNP can be used as nanocarrier (rapid binding to the alveolar epithelium)

[111]

Ferrous and ferric chlorides

Antibody conjugates

Controlled precipitation approach

∼350 nm

Intravenous

Enable endothelial delivery of active ingredients and protected from proteolysis CAT and SOD

[106]

Cerium oxide (IV) nanoparticles

SOD and CAT

 

2–3 nm

SOD enzymatic assay

Against ROS

[112]

Al2O3 NPs

Al2O3

(Purchased from Plasmachem Gmb)

 

Inhalation

Al2O3 NPs exposure lead to suppression of PTPN6 and phosphorylation of STAT3. rescue of PTPN6 expression or application of a STAT3 inhibitor which protect lungs from inflammation and apoptosis

[113]

Biodegradable nanoparticles

Poly(ε-caprolactone)

Lipoic acid

Interfacial polymer deposition

191–349 nm

In vitro lipid peroxidation system

Protection against lipid peroxidation

[114]

HPOX

HBA

Single emulsion method

~ 450 nm

RAW 264.7 cells and in vivo intranasally

inhibit NO production by suppressing iNOS expression in LPS-activated cells

[115]

polyoxalate

HBA

Conventional single emulsion method

~ 500 nm

Intratracheally, injection

Scavenge H2O2, suppress the expression of iNOS, COX-2, (IL)-1β

[116]

Poly(trolox ester)

trolox

Single-step emulsion technique

120–220 nm

U937 cells

Enzymatic degradation to release active antioxidants and suppress almost 50% of oxidative stress in the cells

[117]

Polymer nanoparticles

PHEA-PLA-PEG2000

FP

HPH (freeze drying)

161.3 ± 4.14.0 nm

Immortalized normal bronchial epithelial cell line

Improve drug permeation through the mucus layer, reduce the survivin expression

[118]

PEG-DSPE

Budesonide

HPH (freeze drying)

∼550 nm

Inhalation

–

[119]

PVP; PVA or dextran

Curcumin

Solvent and antisolvent precipitation method

30 nm

Inhalation

Inhibit LPS-induced inflammation in alveolar macrophages in a time dependent manner

[120, 121]

PGA-co-PDL, cationic lipid DOTAP

microRNAs

Single emulsion solvent evaporation method

244.8 ± 4.40 nm

Human alveolar adenocarcinoma A549 cells

Reduce IRAK1 expression and dampen IL-8 promoter reporter output

[122, 123]

PLGA, calcium phosphate, chitosan or PEI

siRNA, pDNA, FITC-BSA

Modified the rapid precipitation method (freeze drying)

Below 200 nm

HeLa cells

Increase the encapsulated siRNA or DNA and help them across the cell membrane

[124, 125]

PLGA, calcium phosphate, polyethylenimine

siRNA

Modified the rapid precipitation method (freeze drying)

~ 145 nm

Nasal instillation

Regulate the expression of IFN-γ, CCL-2 and IP-10 to achieve a decreased inflammation of the lungs

[124, 125]

Dendrimers

PEGylated polylysine dendrimers

–

[126]

11–78 kDa

Pulmonary instillation

Control delivery of medications to lungs by modified with variously sized PEG groups in particle surface

[127]

PAMAM dendrimers (PEGylated or not)

–

–

5.1–9.9 nm

Pulmonary delivery pharyngeal aspiration (P.A.) technique

Enhance dendrimer reaching the endothelial cells and systemic circulation. P.A. administration promotes the passive targeting of dendrimers to lymph nodes

[128]

TEE modified PAMAM dendrimers

siRNA

Vortex

257 nm

Inhalation

Target lung alveolar epithelial A549 cells and silence genes

[129]

PAMAM dendrimer

TNF-α siRNA

Vortex

127–153 nm

RAW264.7 cells, intranasal in acute lung inflammation model

Gene silence (targeted TNF-α)

[130]

Polymer hybrid nanoparticles

PLGA and DOTAP

siRNA

DESE

Below 250 nm

H1299 cells

Gene silence (targeted TNF-α)

[131]

PLGA and DOTAP

pHDAC2, MnPD

Modified solvent displacement method

 ~ 120 nm

A549 cells

Reduce ROS level and glucocorticoid resistance

[123]

Nanocrystals

Pluronic F68 or lecithin

Budesonide

Wet-milling technique

150–400 nm

–

Facilitate easier industrial use of nanocrystals

[132]

Multifunctional nanomaterials

Fibroin

Sulforaphane, CeNPs and PEI passivated CDs

Modified solvent displacement method

365 ± 20.2 nm

Cell evaluation

Against oxidative stress and imaging

[133]

  1. DESE: double emulsion solvent evaporation method; HBA: p-Hydroxybenzyl alcohol; trolox: antioxidant and water-soluble analogue of Vitamin E; Al2O3 NPs: aluminum oxide nanoparticles; FP: fluticasone propionate; HPH: high-pressure homogenization; PLGA: poly(lactide-co-glycolide); HPOX: HBA-incorporated copolyoxalate; LPS: lipopolysaccharide; COX-2: cyclooxygenase-2; U937: Human leukemic monocyte lymphoma cells; PEG-DSPE: Polyethylene glycol and phosphatidylethanolamine; PVP: polyvinylpyrrolidone; PVA: polyvinyl alcohol; PGA-co-PDL: poly (glycerol adipate-co-ω-pentadecalactone; DOTAP: dioleoyltrimethy- lammoniumpropane; PLA: poly(lactic acid); pHDAC2: HDAC2-encoding plasmid DNA; MnPD: Mn-porphyrin dimer; CeNPs: cationic cerium oxide nanoparticles; CDs: carbon dots