Table 2.
Comparative analysis of anti-stroke drugs and their nano formulations.
| S. No. | Drug | Nanocarrier | Surfactants used for nanocarrier | Animal Model | Route | Dose | Molecular Target(s) | Significant Findings | Ref. | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Free Drug | Drug-NP | Free Drug | Drug-NP | ||||||||
| 1. | Curcumin | SLNP | Tween 80 and Lecithin | Male Wistar Rats; BCCAO (n=6) | Oral | 25 & 50 mg/kg b.wt. | 25 & 50 mg/kg b.wt. | Xanthine/Xanthine Oxidase System; Other ROS systems | No effect on body weight & temperature in I/R group No effect on locomotor activity in I/R group Increased memory consolidation in MWM No significant effects on levels of SOD, catalase, GSH, mitochondrial complex enzymes, LPO, nitrite and AChE levels Poor bioavailability due to first pass metabolism |
Increased body weight and restored normal temperature in I/R group Significantly restored locomotor activity in I/R group Better memory consolidation in MWM as compared to free curcumin treated group Significant increase in levels of SOD, catalase, GSH & mitochondrial complex enzymes and decrease in LPO, nitrite and AChE levels 16.4 times improvement in brain bioavailability as compared to free curcumin |
102 |
| 2. | Curcumin/Demethoxycurcumin/Bisdemethoxycurcumin | Polymeric N-isopropyl acryl amide (PNIPAM) |
- | Wistar Rats; MCAO (n=6) |
IN | 100 µg/kg b.wt. | 100 µg/kg b.wt. | Antioxidant System | Improved locomotor activity Improved grip strength Decreased TBARS level Protection to antioxidant enzymes such as SOD, catalase, GPx and GR |
Significant changes were observed for all behavioral and oxidative stress parameters Antioxidant potential of nano-formulations is: Curcumin>Demethoxycurcumin>>Bisdemethoxycurcumin Significant prevention from I/R injury as compared to other groups |
177 |
| 3. | Resveratrol | SLNP | Lecithin | Male Sprague Dawley Rats; BCCAO (n=5) |
Oral | 10 mg/kg b.wt. | 10 mg/kg b.wt. | Nrf2/HO1 pathway; Mitochondrial Oxidative Stress | Bioavailability in brain: 7.01 ± 0.53 μg/g | Bioavailability in brain is higher than free RSV: 31.37 ± 0.32 μg/g Significant reduction in escape latency and path length and 2.5-fold increase in path efficiency as compared to BCCAO rats in MWM experiment Significant reduction in mitochondrial ROS production, LPO and protein carbonyls in BCCAO rats Significant reduction in HIF-1α levels Significant increase in Nrf2 and HO-1 levels |
173 |
| 4. | Panax Notoginsenoside | Hybrid Liposomal Vesicles | Polyvinylalcohol | Male Sprague Dawley Rats; BCCAO (n=10) |
Oral | 30 mg/kg b.wt. | 30 mg/kg b.wt. | Antioxidant System | Attenuation of brain infarction induced by I/R injury No significant restoration of antioxidative enzymes levels |
Significant attenuation of I/R induced brain infarction as compared to free drug solution Significant restoration of antioxidant enzymes levels near to normal levels such as LDH, MDA, H2O2 and SOD. |
201 |
| 5. | Quercetin | Polylactide-co-glycolide (PLGA) | - | Male Sprague Dawley Rats (Young and Aged); BCCAO (n=6) |
Oral | 2.7 mg/kg b.wt. | 2.7 mg/kg b.wt. | Mitochondrial Antioxidative System | No significant downregulation of iNOS and caspase-3 activities No significant improvement in neuronal cell count in hippocampal CA1 and CA3 regions in both young and aged rats |
Significant downregulation of iNOS and caspase-3 activities Improved neuronal count in hippocampal CA1 and CA3 region in both young and aged rats Complete protection to mitochondrial membrane in young and aged rats' brain regions |
103 |
| 6. | Puerarin | Hydroxypropyl beta cyclodextrin | - | Male Wistar Rats; MCAO (n=8) |
Oral | 05 mg/kg b.wt. | 05 mg/kg b.wt. | BBB permeability | Poor bioavailability and BBB infiltration Reduction in mean infarct volume in MCAO rats as compared to control group Improvement in cortical EEG power, peak, area and frequency as compared to control group |
Enhanced drug bioavailability and BBB penetration Significant reduction in mean infarct volume in MCAO rats as compared with control and free drug groups Significant infiltration of inflammatory cells and alleviation of neuronal pyknosis and karyolysis Significant mitigation of cell apoptosis Significant improvement in cortical EEG power, peak, area and frequency in comparison to control and free drug group |
202 |
| 7. | Rutin | Chitosan | TPP | Wistar Rats; MCAO (n=6) |
IN | 10 mg/kg b.wt. | 10 mg/kg b.wt. | BBB permeability | Nose to brain direct transport percentage: 29.48 ± 1.05% Poor brain bioavailability Significant improvement in locomotor activity and grip strength of MCAO rats as compared to control group only |
Nose to brain direct transport percentage: 93.00 ± 5.69% Significant improvement in brain bioavailability, locomotor activity and grip strength in MCAO group as compared to free rutin application intranasally |
176 |
| 8. | C3 siRNA | Cationic lipid assisted PEG-PLA | - | Male C57BL/6 J mice; MCAO (n=3) | IV | 01 mg/kg b.wt. | 01 mg/kg b.wt. | Microglia | Reduced localization of C3 siRNA in ischemic region No significant decrease in the levels of inflammatory cytokines such as TNF-α No major effect on pro-apoptotic factor like caspase-3 No significant reduction in infarct size post I/R insult |
Inhibited the in vitro increase of microglial C3 expression induced by hypoxia/re-oxygenation BBB penetration and delivery of C3 siRNA in ischemic region Significant reduction in microglia induced neuronal damage and TNF-α levels post I/R injury Prevented apoptosis and reduced ischemic penumbra Substantial improvement in functional recovery post ischemia |
203 |
| 9. | TNF-α | Poly(ethylene glycol)-b-(poly(ethylenediamine l-glutamate)-g-poly(l-lysine) PEG-b-(PELG-g-PLL) |
- | Male Sprague Dawley Rats; BCCAO (n=20) |
Injection into cisterna magna | 01 µg/kg b.wt. | 10.92 µg/kg b.wt. (containing 01 µg/kg b.wt. TNF- α) | Inflammatory pathway; Oxidative Stress system | Significant reduction in brain edema ratio as compared to sham group Significant increase in SOD level and decrease in MDA level as compared to sham group Levels of anti-inflammatory cytokines are increased and pro-inflammatory cytokines are decreased as compared to sham group Significantly downregulated the expressions of pro-apoptotic factors as compared to sham group |
Significant reduction in brain edema ratio as compared to free TNF-α group Significant increase in SOD level and decrease in MDA level as compared to free TNF-α group Levels of anti-inflammatory cytokines are increased and pro-inflammatory cytokines are decreased as compared to free TNF-α group Significantly downregulated the expressions of pro-apoptotic factors as compared to free TNF-α group |
108 |
| 10. | Catalase and SOD | PLGA | - | Male Sprague Dawley Rats (n=3) |
ICA catheter | 02 mg/kg b.wt. (tPA) | 08 mg/kg b.wt. (Catalase) and 04 mg/kg b.wt. (SOD) | Inflammatory pathway; Oxidative Stress system | Fewer presence of radial glia like neural precursor cells and nestin positive cells after tPA treatment only Large number of caspase positive cells and neutrophils No significant prevention from brain edema post tPA treatment |
Widespread distribution of radial glia like neural precursor cells and nestin positive cells Fewer caspase positive cells and neutrophils Inhibited brain edema and protected BBB from ROS |
204 |
| 11. | Edaravone | PEG-PLA Agonistic Micelles | A2AR agonistic agents | Male ICR mice; MCAO (n=5) | IV | 0.45 μmol | 0.45 μmol | BBB permeability | Less drug availability in brain | Up-regulated endothelial monolayer permeability More drug availability in brain compared to other groups Accelerates axonal remodeling post ischemia Improves functional behavior in ischemic stroke model |
205 |
| 12. | Lycopene | Liposomes | - | Male Sprague Dawley Rats; MCAO (N=69) |
Intragastric | 06 mg/kg b.wt. | 06 mg/kg b.wt. | Iron regulating proteins | Reduction in infarct volume Significant reduction in apoptotic cells compared to sham group only Reduced oxidative stress levels compared to sham group Limited suppression of iron regulating proteins Limited suppression of IL-6 release post ischemic insult |
Significant reduction in infarct volume compared to free lycopene Significant suppression of apoptosis and oxidative stress Significant suppression of iron regulating proteins like hepcidin and ferroprotein, thus normalizing the iron levels post ischemia Attenuate the release of IL-6 |
206 |
| 13. | Squalenoyl Adenosine (SQAd) | SQAd Nano- assemblies | - | Male Swiss Albino Mice; MCAO (n=6) | IV | 5.5 mg/kg b.wt. | 7.5 or 15 mg/kg b.wt. | Cerebral Micro vessels | Reduction in infarct volume as compared to vehicle group | Significant reduction in infarct volume in ischemic rats as compared to other groups Significant reduction in the apoptotic process in ischemic region Significant improvement in microcirculation |
207 |
| 14. | Gallic Acid | O-Carboxymethyl Chitosan | - | Male Sprague Dawley Rats; MCAO (n=8) |
Oral | 50 mg/kg b.wt. | 50 mg/kg b.wt. | Inflammatory pathway | Significant reduction in infarct volume as compared to control group Reduction in TUNEL-positive cells in comparison to sham group Low anti-inflammatory effects compared to nano group |
Best protective effect on infarct size Fewer TUNEL-positive cells post ischemia Significant reduction in TNF-α and IL-1β levels and increase in SOD and catalase levels indicating strong anti-inflammatory effects |
99 |
| 15. | Osteopontin | Gelatin microspheres | - | Male Sprague Dawley Rats; MCAO (n=3-6) |
IN | 01 µg/rat | 01 µg/rat | - | 70.22% reduction in infarct size post ischemia Therapeutic effects are seen only if administered within 6 h post MCAO surgery |
Enhanced neuroprotective effects of Osteopontin 71.57% reduction in infarct size post ischemia Extension of therapeutic window of IN administered drug to at least 6 h post ischemia |
208 |
| 16. | NR2B9c Peptide | PEG-PLGA | Wheat Germ Agglutinin | Rats; MCAO (n=7-8) | IN | 0.3 mg/kg b.wt. | 0.3 mg/kg b.wt. | NMDAR | Lower drug availability in brain No significant effect on infarct size and neurological deficit score |
Greater bioaccumulation in damaged region due to MCAO Significant reduction in infarct size and neurological deficit scores |
209 |
| 17. | 17β-Estradiol | Gelatin | - | Male C57BL/6J Mice; MCAO (n=4) | IN | - | No significant effect on infarct volume | 5.24-fold increase in estradiol content in brain 54.3% reduction in infarct volume on 100 ng dose |
210 | ||