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. 2022 Dec 21;13(1):47–79. doi: 10.1039/d2ra06410c

Results of various studies over the past decade showing efficacies of different drug carrier systems with relevant parameters. (EE1: encapsulation efficiency, EE2: entrapment efficiency).

Antiviral Drug Nanoparticle(s) Action against virus Route of administration In vitro/in vivo/ex vivo Size (nm) Polydispersity index [PDI] Synthesis method Efficiency Reference
Acyclovir SLNs [HSV]-TK In vitro 180 nm Emulsification and low-temperature solidification method 78% EE2% 124
PEGylated lipid polymeric NPs HSV-1 and HSV-2 Oral In vitro, ex vivo 187.7 ± 3.75 nm 0.179 ± 0.03 to 0.429 ± 0.12 Box–Behnken design (BBD) 83.81 ± 1.93% EE2% 69
Bilosomes NCs HSV-1, HSV-2, and varicella-zoster (VZV) Oral In vitro, in vivo, ex vivo 121.2 ± 3.21 nm 0.261 ± 0.023 Thin-film hydration technique. (Optimize by Box–Behnken statistical design) 71.87–88.67% EE2% 75
Gel nanoemulsions (NEs) HSV Ocular In vitro, in vivo, ex vivo 28 nm to 34 nm 0.38 ± 0.04 to 0.47 ± 0.05 Low energy method 2.8× increase in drug permeation 125
Bovine serum albumin (BSA) NPs HSV Transcorneal/Ocular In vitro 173.0 ± 9.5 to 204.7 ± 15.5 nm 0.079 ± 0.023 to 0.226 ± 0.025 80
PLGA polymer stabilized with TPGS nanosystem HSV Ocular In vitro, in vivo, ex vivo 262.38 ± 11.85 nm 0.255 ± 0.011 58.42 to 80.15% EE1% 81
Carboxymethyl cellulose acetate butyrate NPs HSV Intravenous In vitro ∼125–450 nm Precipitation processes (one simple and other rapid) Drug loading efficiency of 40% 82
Eudragit RLPO® based NPs Oral In vitro 82 ± 3.83 nm to 532 ± 4.86 nm 0.308 ± 0.24 to 0.716 ± 0.25 Nanoprecipitation technique 79.34 ± 1.64% EE2% 126
Chitosan NPs HSV Topical delivery In vitro 240.0 ± 62.4 nm 0.53 ± 0.12 Using cross-linked chitosan with tripolyphosphate (TPP) 16% EE1% 127
Chitosan NPs OVI Ocular In vitro 200–495 nm Ionic gelation technique 56 to 80% EE1% 128
Microemulsions (ME) Herpes virus infections Topical In vitro 6.2 ± 0.2 nm to 15.1 ± 1.5 nm Pseudo ternary phase diagrams 2× fold increase in ACV accumulation 129
β-Cyclodextrin-poly(4-acryloylmorpholine) mono-conjugate (β-CD-PACM) HSV-1 Oral In vitro 150 nm (unloaded) and 200 nm when (loaded) Solvent injection technique 83% EE1% 130
Liposomes HSV Intranasal In vivo 1048.1 ± 101.3 nm and 627.4 ± 36.9 nm (for two methods) Drug lipid film hydration method 43.20% 131
Bovine serum albumin (BSA) NPs HSV Ocular In vitro ∼200 nm Desolvation method 84.59 ± 1.81 and 52.05 ± 2.03 EE2% 132
Adefovir dipivoxil SLNs HBV In vitro 389.4 ± 166.5 −0.371 Solvent diffusion method 15% EE2% 133
Atazanavir Eudragit RL100 NPs (ATV NPs) HIV Oral In vitro, in vivo 465.59 nm 0.372 Nanoprecipitation method 41.3 to 56.9% EE1% 134
Atazanavir and darunavir LNPs HIV Subcutaneous 33.6–35.6 nm Sonication of hydrated lipid–drug suspension 85.5 ± 8.2 [ATV], 85.1 ± 7.1 [RTV], and 6.1 ± 0.8% [TFV] EE2% 135
Atazanavir, efavirenz, and ritonavir Atazanavir, efavirenz, and ritonavir NPs (nano ART) HIV-1 Parenteral administration 300–645 nm High-pressure homogenization 136
Azidothymidine Galactosylated liposomes AIDS6 Intravenous In vitro 120.01 ± 2.11 nm Esterification of galactose EE2% (L1 to L4): 42.35 ± 0.38, 54.26 ± 3.25, 36.69 ± 3.10, 31.44 ± 2.22 (%) 137
Atazanavir and darunavir Lipid polymer hybrid NPs (LPHNs) HIV Oral In vitro 50 nm One-step optimized nanoprecipitation method 62, 68.1 and 68.5% w/w EE1% 138
Dolutegravir Chitosan-based polymeric NPs HIV Oral 140–548 nm 3-Step process demineralization, deproteinization, and deacetylation - 139
Dolutegravir sodium β-Cyclodextrin-based NPs Neuro-AIDS Intranasal In vitro, in vivo 72.47 ± 4.8 to 106.5 ± 5.6 nm 0.306 ± 0.002 and 0.475 ± 0.004 Cross-linking hydroxypropyl β-cyclodextrin (HPβCD) with diphenyl carbonate 77 ± 3.35% EE2% 140
Efavirenz Chitosan NPs HIV Oral In vitro ±104 nm Ionotropic gelation method 91.09% EE2% 141
Eudragit E100 HIV/AIDS Oral In vitro, in vivo 110 ± 5 nm 0.201 ± 0.05 Emulsion solvent evaporation method 99% EE2% 84
Lactoferrin NPs HIV Oral In vitro, in vivo 45 ± 60 nm <0.341 Sol-oil protocol 2× times improved anti-HIV-1 action compared to free EFV 85
SLNs HIV Oral In vitro, in vivo 168 nm <0.220 Hot homogenization technique followed by ultrasonication method 60 ± 5% EE2% 142
SLNs HIV Oral In vitro 124.5 ± 3.2 nm 0.234 86% EE2% 143
Poly(epsilon-caprolactone) (PCL) NPs HIV/AIDS Oral In vitro, in vivo 200–250 nm Narrow Double-emulsion/spray-drying method 86–93% EE1% 144
Nanoemulsion of EFV HIV/AIDS Oral In vitro, in vivo Less than 30 nm Phase inversion composition method 80% release within 6 hours 145
Chitosan-g-HPβCD NPs Neuro-AIDS Intranasal In vitro, in vivo 198 ± 4.4 nm 0.325 ± 0.004 to 0.675 ± 0.005 Ionic gelation method 38 ± 1.43% EE2% 145
Efavirenz (EFV) and lopinavir/ritonavir (for boost) PLGA NPs HIV Intracellular In vitro 138.3–55.4 nm High-pressure homogenization method >79% EE2% 146
Efavirenz and nevirapine SLNs HIV/AIDS In vitro 128.7 nm to 182.2 nm Modified emulsion/microemulsion procedure EFV ∼98% and NVP ∼30% EE2% 147
Elvitegravir PLGA-EVG NPs HIV-1 Intraperitoneally In vitro, in vivo Less than 200 nm Nano-precipitation technique ∼95% loading efficiency of drug 148
PLGA-EVG NPs HIV-1 In vitro ∼47 nm - Nano-precipitation technique ∼92% EE1% 149
Enfuvirtide and protoporphyrin IX Nano-liposome HIV-1 Intravenous and intramuscular administration In vitro Surfactant-based nanoparticles A rapid extrusion procedure 150
Foscarnet Chitosan NPs HIV-1, herpesvirus DNA polymerase Oral, topical In vitro, in vivo 292 ± 5 nm to 497 ± 13 nm 0.26 ± 0.01 to 0.78 ± 0.21 151
Griffithsin (GRFT) (an anti-viral lectin) mPEG-PLGA GRFT NPs HIV-1, HSV-2 Topical In vitro, in vivo 152 to 345 nm Double emulsion solvent evaporation technique 85.6 ± 11.0 EE1% 152
Indinavir Lipid nanoemulsion (LNE) HIV Intravenous In vitro, in vivo 200.1 ± 73.2 nm (lowest value) 0.05 ± 0.04 98.8%, 98.9% and 99.0% EE2% 109
Monoolein-based NPs HIV Oral In vitro 155 ± 7 nm 0.16 ± 0.03 Magnetic stirring and high-pressure homogenization 96% drug incorporation efficiency 108
mPEG-PCL NPs HIV Oral In vivo 211 ± 10.12 nm (mean particle size) 0.22 to 0.68 Emulsification solvent evaporation method 60%, 40% and 15% drug release percent 107
Indinavir and lactoferrin Nanoemulsion HIV Drug injection In vitro, in vivo 112 ± 3.5 nm 0.20 ± 0.02 High-speed homogenization method - 153
Ivermectin Ivermectin NPs ZIKV Oral In vitro, in vivo ∼65 nm Conjugation efficiency of ∼60% for empty NPs and ∼40% for 20% IVM feed loaded NPs 154
Lamivudine Chitosan NPs HIV-1 Oral In vitro, in vivo 120.7 ± 3.1 nm [CS-NPs]; 145.8 ± 4.2 [GL-LMWC-NPs] 0.09 ± 0.01 [CS-NPs]; 0.11 ± 0.06 [GL-LMWC-NPs] Depolymerization followed by ionotropic gelation method 71.37 ± 1.19% EE1% 117
MLNs Topical (semisolid) or oral (after resuspension) In vitro ∼450 nm <0.3 Hot homogenization method in conjunction with high shear and ultrasonication 118
Lopinavir SLNs HIV/AIDS Oral In vivo 196.5 ± 3.5 nm 0.11 ± 0.01 Warm oil-in-water (O/W) micro-emulsion technique EE (%) 76.5 ± 3.5% 101
In situ self-assembly nanoparticles (ISNPs) HIV Oral In vitro, in vivo Less than 158 nm Warn microemulsion precursors with modification 95% EE2% 100
PLGA NPs HIV/AIDS Oral In vitro, in vivo 142.1 ± 2.13 nm Solvent diffusion (nanoprecipitation) method 93.03 ± 1.27% EE2% 155
Pullulan acetate NPs HIV/AIDS Oral In vitro, in vivo 197 ± 4 nm (∼197 nm) <0.2 Motozato's method 75% EE2% 103
Poly-e-caprolactone (PCL) nanoparticles (NPs) HIV/AIDS Oral In vitro, in vivo, ex vivo 195.3 ± 2.3 nm 0.10 ± 0.01 Oil-in-water emulsion-solvent evaporation technique 93.9% EE2% 156
SLNs HIV/AIDS Oral In vitro, in vivo 180.6 ± 2.32 nm 0.133 ± 0.001 Hot self-nano emulsification (SNE) technique 91.5 ± 1.3% EE2% 102
Compritol®-SLNs HIV/AIDS Oral In vivo 156 nm Hot homogenization method followed by ultrasonication 98.99% EE2% (highest) 157
Lopinavir–ritonavir–tenofovir Drug-combination nanoparticles (DcNPs) HIV Subcutaneous In vitro Aseptic technique Highest drug association efficiency of 99 ± 8.2% for lopinavir, 92 ± 7.1% for ritonavir and 10 ± 0.8% for tenofovir 158
Nevirapine Mesoporous silica nanoparticles (MSNPs) HIV-1 In vitro 60 nm Stober's method 159
PS80-coated PCL NPs HIV/AIDS Intravenous In vitro, in vivo 218.3 ± 7.3 nm 0.283 ± 0.038; 0.179 ± 0.00 Emulsion solvent evaporation technique 50.71% EE2% (highest) 160
Cellulose acetate butyrate (CAB) NPs HIV/AIDS In vitro 305.76 ± 5.7 nm 0.29 ± 0.03 Emulsification solvent evaporation method 75.89 ± 1.36% EE1% 161
Nanoliposomes HIV/AIDS In vitro 157 nm Thin-film hydration 78.14% and 76.25% EE1% 162
Oseltamivir SeNPs EV71 In vitro 10 nm 50
Raltegravir + efavirenz PLGA NPs HIV Intravaginal In vitro 81.8 ± 6.4 nm Emulsion–solvent evaporation method 55.5% [RAL] and 98.2% [EFV] EE1% 163
Ritonavir SLNs HIV-1 Oral In vitro 170–250 nm 0.2 Solvent emulsification method and double emulsion method 53.2% EE2% 164
SLNs HIV/AIDS Oral In vitro, in vivo Less than 300 nm 0.361 Solvent evaporation followed by ultrasonication 53.20 ± 4.13 to 73.04 ± 2.85% EE1% 165
PLGA NPs HIV/AIDS 42–102 nm 0.381 Solid-in-oil-in-water (s/o/w) solvent evaporation technique with some changes 75% EE1% 166
Lopinavir (LPN) NPs HIV-1 Oral In vitro, in vivo ∼320 nm <0.2 Antisolvent precipitation and high-pressure homogenization techniques 167
Saliphenylhalamide (SaliPhe) SiNPs Influenza A viruses (IAVs) Inhalation or intravenous (envisioned) In vitro 129 ± 10 nm 0.112 168
Saquinavir SQV NPs HIV Oral In vitro 136–158 nm Interfacial polymer technique > 97% EE1% 105
SQV nanocrystals HIV Oral In vivo, ex vivo 205.93 ± 3.74 nm 0.1 Anti-solvent precipitation high-pressure homogenization method 106
Chitosan NPs AIDS In vitro 10–200 nm Ionic gelation technique 72% EE1% 169
SLNs HIV/AIDS Intravenous 120 nm to 450 nm 170
SLNs HIV Oral In vitro, in vivo 215 ± 9 nm [SQSLNs]; 344 ± 16 nm [SNS] 0.196 ± 0.019 of SNS Hot high-pressure homogenization (HPH) method 79.24 ± 1.53% EE2% 104
Stavudine Chitosan NPs HIV Oral In vitro 212 nm (PSD) Ionic gelation of chitosan with tripolyphosphate anions 85.8 ± 0.16% EE2% (highest) 171
SLNs HIV-1/AIDS Intravenous In vitro, in vivo, ex-vivo 75 ± 1.22 nm 0.12 Homogenization High labeling efficiency 172
Mannosylated liposomes HIV Intravenous In vitro, in vivo 120 ± 1.52 nm Esterification of mannose 47.2 ± 1.57% EE2% 173
Stavudine, delavirdine, and saquinavir SLNs HIV/AIDS 142–294 nm Involves emulsion 174
Tenofovir Thiolated chitosan (TCS) core/shell nanofiber (NF) HIV-1 Topical In vitro, in vivo 58.81 nm - Coaxial electrospinning technique 95% (in 5 hours) 123
Chitosan NPs HIV Vaginal route In vitro 545.1 ± 69.17 nm 0.663 ± 0.107 Ionic gelation 6.8 ± 3.1 EE1% 121
(PLGA)/stearylamine (SA) composite NPs HIV Vaginal route In vitro, in vivo, ex vivo 127 ± 1 nm 0.27 ± 0.01 Double emulsion/solvent evaporation method Drug association efficiency >50% 120
Chitosan–thioglycolic acid-conjugated (CS–TGA) NPs HIV/AIDS Topical In vitro 240.1 nm CS NPs; 252.3 nm CS-TGA-NPs 0.298 ± 0.002 [CS]; 0.317 ± 0.052 [CS-TGA] Ionotropic gelation 22.60% EE1% 122
PLGA NPs loaded with efavirenz NPs or saquinavir NPs HIV-1 BaL infection Topical In vitro 227 ± 1.8 nm [EFV]; 189 ± 96.3 nm [SQV] 0.05 [EFV]; 0.486 [SQV] Emulsion or nanoprecipitation techniques 44.5 ± 2.7 [EFV] and 48.3 ± 15.2 [SQV] 175
Tenofovir, alafenamide and elvitegravir TAF + EVG NPs HIV Subcutaneous In vitro, in vivo 190.2 ± 2.3 nm 0.14 ± 0.01 Oil-in-water emulsion solvent evaporation technique 54.1 ± 3.6 [TAF] and 44.6 ± 2.4% [EVG] EE1% 176
Tenofovir alafenamide Emtricitabine (FTC) loaded NPs HIV-1 Subcutaneous and oral In vivo, ex vivo 233.2 ± 12.8 nm 0.11 ± 0.05 Oil-in-water emulsion solvent evaporation technique 69.2 ± 14.5% [TAF] and 65.9 ± 18.2% [FTC] EE1% 177
Tenofovir disoproxil fumarate Chitosan NPs HIV/AIDS Oral In vitro, in vivo, ex vivo 156 ± 5 nm 0.16 ± 0.06 Ionic gelation technique 48.2 ± 1% EE2% 178
Valacyclovir PLA-PEG NPs HSV Oral In vitro, in vivo ∼30 nm Nanoprecipitation 11.4 ± 0.5 EE2% (highest) 179
SLNs HSV Ocular In vitro, in vivo, ex vivo 202.5 ± 2.56 nm 0.252 ± 0.06 Solvent emulsification/evaporation method 28.01 ± 1.89 to 58.82 ± 2.45% EE2% 180
Zidovudine NLCs HIV Oral In vitro 100 to 300 nm < 0.3 Hot ultrasonication and microwave assisted method 44 ± 3%, 22 ± 2% EE2% 181
Alginate NPs HIV/AIDS Intravenous In vitro 432 ± 11.9 nm Emulsion solvent evaporation method Loading efficacy of 29.5 ± 3.2% 88
Lipid NPs modified with polymer gelatin HIV/AIDS Oral and topical In vitro 224 ± 31.2 nm [PLNs of SA]; 291.2 ± 38 nm [PLNs of comp] 87.4 ± 0.58% EE1% 89
Nanosized polyelectrolyte complexes (PECs) HIV In vitro 100–200 nm 0.125–0.305 Drug release of 38.1% at pH 4.5 and 31.2% at pH 7.4 182
SLNs HIV Parenteral, oral, ophthalmic, and topical 222–227 nm [AZT-SA], 402 nm to 434 nm [AZT-SA-AV] 0.2 to 0.3 [AZA-SA], 0.38–0.45 [AZT-SA-AV] Simple emulsion solvent evaporation method 74.92 ± 1.2% EE1% 92
Chitosan NPs AIDS Nasal 260 ± 1.70 nm, 330 ± 12.9 [NP1, NP2]; 406 ± 14.0 and 425 ± 14.5 for AZT-loaded NP1 and NP2 0.247, 0.329, 0.390, 0.381 Ionotropic gelation method 17.58% ± 1.48 and 11.02% ± 2.05 EE2% for NP1 and NP2 183
Lipid-polymer hybrid NP HIV In vitro 175 ± 2.5 nm 0.196 Melt emulsification-probe sonication technique 6.5 ± 0.50 to 49.26 ± 0.75% EE2% 184
PLA–PEG blend NPs AIDS Intranasal In vivo 328.1 ± 8.6 nm 0.383 Double emulsion–evaporation method 52% EE1% 185
SLNs AIDS Oral In vitro 621 nm W/o/w double-emulsion solvent–evaporation method 27% EE2% 186
Dextran and stearic acid NPs HIV/AIDS Intravenous In vitro, in vivo 356 nm to 730 nm Double emulsion solvent evaporation method 93.46% EE1% 86
PVP/SA-PEG NPs (PSNPs) AIDS Intravenous In vitro 341 ± 4.34 nm 0.3 ± 0.04 Emulsification-solvent evaporation method 37.19% to 79.2% 87
Hybrid NPs of CMC-AZT core enclosed by shell of Comp-PEG AIDS Oral In vitro 161.65 ± 44.06 nm 82% EE1% 90
Zidovudine + efavirenz + lamivudine Lactoferrin NPs HIV Oral In vitro, in vivo 67 nm Sol-oil protocol 58 to 71% EE1% 187