Table 1.

AMP encapsulated lipid-based nanoparticles applicable for treatment of various bacterial infections.

Type of Nanoparticles and Particle Composition	AMP	Physicochemical Properties (Size, Surface Charge, Encapsulation Efficiency, Release)	In Vitro and In Vivo Results	Application	Refs.
Liposomes
SCS-Lipoid® S75 SPC liposomes	Colistin	113–137 nm, −66 to −53 mV, EE = 84–92%, 15–43% release in 24 h	-Maintained antimicrobial activity against P. aeruginosa */** -Increased lung retention, reduced systemic exposure and enhanced efficacy in pulmonary infection model in mice *	Systemic/pulmonary infections	[41,85]
Surface-modified liposomes
CHL-DSPC-DSPE-mPEG2000 liposomes	LL-37 Indolicidin	107 nm, −2.1 mV, EE = 53% (LL-37) 121 nm, −3.1 mV, EE = 35% (indolicidin)	-Faster and enhanced LL-37 uptake by HaCaT cells * -Reduced cytotoxicity against HaCaT cells/3D Ker-CT model * -Enhanced LL-37 antiviral effect against HSV-1 virus *	Topical/intracellular infections	[20]
CHL-DOPE-lecithin liposomes coated with chitosan	Colistin	485 nm, +5.3 mV	-Antimicrobial activity enhanced against susceptible and maintained against MDR strains of P. aeruginosa */** -Empty liposomes have intrinsic antimicrobial activity	Systemic/pulmonary infections	[47]
CHL-S60-lecithin liposomes coated with chitosan	Colistin	156 nm, +16.7 mV, EE = 45–82%, 85% release in 24 h	-Bioavailability improved in thigh muscle infected mice * -Improved localization at the E. coli-infected muscle *	Oral delivery/systemic infections	[48]
CHL-DPPC/DSPC-DPPE-GA liposomes coated with EAP	Colistin	203 nm, −15.3 mV, EE = 51%, 20% release in 5 h in PBS or GIT-mimicking media	-Mediated internalization into epithelial cells -Reduced intracellular S. enterica load in Hep-2/Caco-2 cells ***	Oral delivery/intracellular infections	[22]
Red blood cell (RBC)-mimetic hybrid liposome composed of lipid S100-DSPE-PEG2000	Polymyxin B	~150 nm, −28 mV	-Prevents hemolysis (neutralization of α-hemolysin and LPS) -Prolonged survival in toxin infected mouse model *** -Only protective at early stage in subcutaneous E. coli infection	Antivirulence therapy	[49]
Coencapsulated liposomes
CHL-HSPC-DMPG/DSPG Liposomes	Ciprofloxacin Colistin	~100 nm, anionic, EE = 67% (colistin), EE = 90% (ciprofloxacin), 50–80% release in 30 min then sustained release	-Maintained antimicrobial activity against P. aeruginosa * -Similar cytotoxicity against A549 cells * -Reduced transport capacity of drugs across the lung epithelial cell monolayer and enhanced retention on lung surfaces *	Pulmonary infections	[50,53]
CHL-HSPC-DSPG-PEG liposomal powder formulation	Ciprofloxacin Colistin	141–378 nm, −21.0 to −9.2 mV, EE = 47–59% (colistin), EE = 32–71% (ciprofloxacin)	-Maintained antimicrobial activity against P. aeruginosa * -Similar cytotoxicity against A459 and Calu-3 cells */** -Reduced transport/enhanced accumulation in Calu-3 cells *	Pulmonary infections	[51,52]
CHL-PC-OA liposomes decorated with AMP2 or AMP3	Vancomycin AMP2/AMP3	137–387 nm, −9.8 to +1.8 mV EE = 27–64%, 49–67% release in 8 h at pH 6, 18–23% release in 8 h at pH 7.4	-Improved antimicrobial activity against MRSA * -No hemolytic activity -Effective against intracellular MRSA	Intracellular infections	[23]
CHL-SPC liposomes incorporating DP7-CHL	Azithromycin DP-7	100–106 nm, +3.7 to +5.3 mV, EE = 97–98% (AZT), DL = 5% (DP7-CHL), ~50% release in 96 h (sustained release)	-Antimicrobial activity against S. aureus and E. coli maintained * -Slightly reduced cytotoxicity against HEK293 and LO2 cells * -Enhanced antimicrobial effect against MRSA in BALB/c mice ***	Topical infections	[54]
Niosomes
Niosomes composed of Span60 and cholesterol	Polymyxin B	257 nm, −22.5 mV, EE = 72%, stability in SGF (86.22% in SGF pH 1.2 and 78.5% in SIF pH 6.8)	-Maintained antimicrobial activity against P. aeruginosa * -Enhanced bioavailability in rat * -No toxicity towards body cells observed in vivo	Oral delivery/intestinal infections	[56]
Solid lipid nanoparticles (sLNPs)
GeleolTM-lecithin-Kolliphor® RH40-Transcutol® sLNPs	Lacticin 3147	81–85 nm, EE = 16% (Ltnα), EE = 84% (Ltnβ)	-Improved antimicrobial activity against L. monocytogenes * -Improved stability against protease α-chymotrypsin *	Oral delivery/intestinal infections	[60]
Crodacol® CS90/Crodacol® C90-Lipoid® S75 SPC sLNPs complexed with sodium alginate	Polymyxin B	203–574 nm, −40.7 to −24.1 mV, EE = 93–94%	-Maintained antimicrobial activity against resistant strains of P. aeruginosa * -Crodacol CS90 lipid also antimicrobial	Topical infections	[61]
Glyceryl monostearate-PC-PVA sLNPs	LL-37 Serpin A1	210–232 nm, −20 to −16 mV, EE = 82–89%, 14% release in 24 h followed by slow sustained release over 15 days	-Improved antimicrobial activity against S. aureus and E. coli */** -Reduced cytotoxicity against BJ fibroblast cells and keratinocytes */** -Promotes wound healing in vitro	Topical infections	[62]
Nanostructured lipid carriers (NLCs)
Precirol® ATO 5-Miglyol 812-Polysorbate 80-Poloxamer 188 NLCs	Colistin	300–427 nm, negatively charged, EE = 80–95%, sustained release with >50% release in 24 h	-Maintained antimicrobial against planktonic P. aeruginosa and killed P. aeruginosa in biofilm more rapidly * -More effective killing of bacteria in inner part of biofilm *	Pulmonary infections/biofilm removal	[64,65]
Precirol® ATO 5-Miglyol 182 N/F-Tween® 80-Poloxamer 188 NLCs	Colistin	354 nm, −20.4 mV, EE = 95%, 80% release in 5 h and 92% in 24 h	-Antimicrobial activity reduced against MDR/XDR P. aeruginosa * -Same effectivity at lower concentrations in BALB/c mice *	Systemic/pulmonary infections	[66]
Precirol® ATO 5-Miglyol 812N-Tween® 80-Poloxamer 188 NLCs	LL-37	274 nm, −31.6 mV, EE = 96%, DL = 17%	-Reduced antimicrobial activity against E. coli * -No cytotoxicity against human foreskin fibroblasts -In vivo, wound healing significantly improved *	Topical infections/chronic wounds	[67]
Coencapsulated NLCs
CP-CCP-Lipoid® S100 SPC-PL-SLS NLCs coated with polymyxin B	Dexamethasone acetate Polymyxin B	231–256 nm, −2.1 to +3.5 mV, EE = 94% (dexamethasone acetate), EE = 99% (polymyxin B coating)	-MIC enhanced against P. aeruginosa and B. bronchiseptica * -No cytotoxicity against mammalian fibroblast cells	Ocular infections accompanied by inflammation	[68]
Softisan154-MCT-Kolliphor® P188 NLCs coated polymyxin B and surface modified with chitosan or dextran	Buparvaquone Polymyxin B	184 nm, −20.1 mV (BPQ-NLC-PB-[chitosan]); 209 nm, +31.1 mV (BPQ-NLC-PB-[dextran]); 172 nm, −30.9 mV (BPQ-NLC), EE = 99.3–99.7% (BPQ)	-Coating and decorating with PB improved MIC values against L. infantum infected microphages (~2-fold) * -Coating and decorating with PB increased cytotoxicity against macrophages (3-fold for chitosan, 70-fold dextran) *	Intracellular infections	[69]
Lipid nanocapsules (LNCs)
Labrafac WL1349-Lipoid S75-Kolliphor HS15-NaCl LNCs (adsorption strategy)	AA230 DPK-060 LL-37	60–77 nm, −3.7 to −0.8 mV, EE = 26–35%	-Antimicrobial activity maintained or improved against strains of S. aureus, MRSA, P. aeruginosa, E. coli and A. baumannii * -Stability against proteases improved *	MDR infections	[71]
Reverse micelles in Oleic Plurol-Kolliphor HS-15-Labrafac WL 1349-NaCl-DSS LNCs	AP138	63 nm, −25.6 mV, EE = 98%, 50% release in 2 h, 100% release in 24 h	-Maintained antimicrobial activity against S. aureus/MRSA * -Partial protection against protease trypsin	Topical infections	[72]
ML-Solutol® HS15-Labrafac® WL1349-NaCl LNCs	AP114 AP138	36–37 nm, AE = 34–62%, DL =1–3%	-Maintained potent bactericidal activity against S. aureus * -Synergism with ML-LNC against MRSA/MSSA	Topical infections	[73]
ML-Solutol® HS15-Labrafac® CC-NaCl LNCs	DPK-060 LL-37	32–135 nm, +5 to +20 mV, AE = 28–42% (DPK-060), AE = 72–77% (LL-37), sustained release	-Synergy for both AMPs against S. aureus biofilms -DPK-060 LNCs provided faster initial wound healing in mice *	Topical infections	[74]
Cubosomes
Capmul-90 EP/NF cubosomes in Poloxamer 407 gel	DPK-060	200–300 nm (cubosomes), 50–70% release cubosomes in 24 h	-Maintained bacterial activity against S. aureus * -No toxicity observed in skin irritation test	Topical infections	[77]
GMO-Lutrol F127 cubosomes and GMO-OA-Lutrol F127 hexasomes	AP114 DPK-060 LL-37	87–111 nm, −11.1 mV and EE = 27% (AP114), +0.9 mV and EE = 50% (DPK060), +4.5 mV and EE = 81% (LL-37)	-AP114/DPK-060 in cubosomes maintained bactericidal activity against S. aureus, MRSA, P. aeruginosa, E. coli and A. baumannii * -Bactericidal activity lost in hexasomes *	MDR infections	[78]
GMO-Poloxamer 407 cubosomes	LL-37	130 nm, no release in 24 h	-Reduced antimicrobial activity against S. aureus and E. coli * -Protected LL-37 from proteolysis	Topical infections	[79]
Micelles
SDCS micelles	Polymyxin B	126–189 nm, −7.4 to −4.9 mV, EE = 48–57%, >80% release in plasma in 24 h, sustained release	-Maintained antimicrobial activity against planktonic A. baumannii and planktonic/biofilm P. aeruginosa * -Reduced hemolysis and cytotoxicity towards kidney cells *	MDR Gram-negative infections	[82,83]
DSPE-PEG2000 micelles	Aurein-derived AMPs	12–14 nm	-Reduced hemolysis and cytotoxicity against PBMCs * -Enhanced activity in in vivo MRSA abscess mouse model **	Topical infections	[84]
DP7-CHL micelles	DP7	36 nm, +43.8 mV	-Reduced toxicity and increased survival rates in BALB/c mice * -Effective against P. aeruginosa and MRSA infection in vivo -Immunomodulatory effects of DP7-C micelles in mice	Systemic infections	[81]

Acronyms: AE = adsorption efficiency, AMP = antimicrobial peptide, CCP = capric caprylic triglycerides, CHL = cholesterol, CP = cetyl palmitate, DL = drug loading, DMPG = 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, DOPE = 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, DPPC = 1,2-di-O-palmitoyl-sn-glycero-3-phosphocholine, DSPC = 1,2-distearoyl-sn-glycero-3-phosphocholine, DSPE-mPEG2000 = N-[carbonyl-methoxypolyethyleneglycol-2000]-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, DSPE-PEG2000 = 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-polyethylene glycol 2000, DSPG = distearoyl-sn-glycero-3-phosphoglycerol, DSS = dioctyl sodium sulfosuccinate, EE = encapsulation efficiency, HSPC = hydrogenated soybean phosphatidylcholine, MCT = medium chain triglycerides, MDR = multidrug-resistant, ML = monolaurin, GMO = glycerol monooleate, OA = oleic acid, PC = phosphatidylcholine, PEG = polyethylene glycol, PL = polyoxyethylene-polyoxypropylene block copolymer, S60 = Span60, SCS = sodium cholesteryl sulphate, SDCS = sodium deoxycholate sulphate, SGF = simulated gastrointestinal fluid, SLS = sodium lauryl sulfate, SPC = soybean phosphatidylcholine, XDR = extensively drug-resistant; * compared to peptide solution, ** compared to empty nanoparticles or no treatment, *** compared to nonfunctionalized nanoparticles.