| 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
|