Table 1.

Drug delivery strategies of conventional anti-inflammatory drugs investigated in preclinical studies against COVID-19.

Drug carrier	Therapeutic cargo	DDS properties	In vivo model	Administration route	Advantages	Reference
Liposomes (DPPC and cholesterol)	Hydroxychloroquine	Not defined	WT rats	Pulmonary route	Higher and prolonged exposure. Lower cardiotoxicity	[64]
25-HC@DDAB lipid nanovesicles	25-hydroxycholesterol (25-HC)	126.5 nm +93.26 mV	CLP-induced septic mice	Intravenous	Improved cellular uptake of 25-HC and enhanced pulmonary accumulation of NPs. Alleviated lung inflammation and reduced cytokines production (i.e., IL-1β and IL-6, IL-8, and TNF-α).	[65]
Glycyrrhizic acid NPs	Glycyrrhizic acid	70.65 nm, −32.7 mV	MHV-A59-infected mice LPS-induced endotoxemia	Intravenous	Relieved systemic and lung inflammation with reduced production of inflammatory factors, such as IL-1α, IL-1β, IL-6, and IL-12, TNF-α, TGF-β, IFN-γ, IP-10, G-SCF, and MCP-1	[66]
Polydopamine-modified PEG-PLGA NPs	DNase-1	220 nm, −12.0 mV	CLP-induced septic mice	Intravenous	Enhanced stability and prolonged circulation of DNase-1 Reduced NETosis factors neutralize the activity of neutrophils.	[67]
Squalene lipid NPs	α-tocopherol adenosine	71.2 nm −14.29 mV	LPS-induced endotoxemia	Intravenous	Enhanced accumulation in inflamed lungs. Enhanced IL-10 levels and reduced ROS and pro-inflammatory cytokines production (i.e., TNF-α, MCP-1, and IL-6)	[68]