Table 3.

Relevant studies focusing on nanoparticle-based therapy for COPD

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]

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