Table 2.
Other brain pathologies models and Nanotech applications.
| PATHOLOGY | TARGETING (BBB/tumor) | APPROCHES | DRUG | MODEL | TEST | Results | REF |
|---|---|---|---|---|---|---|---|
| Epilepsy | / | LPs (PC:CHOL:Sterylamine 7:2:1) | PHT or HRP | Rats with status epilepticus | Anticonvulsivant effect Analysis of HRP reaction products in the brain | Suppression of AM discharges by two doses of L-PHT; accumulation of HRP (by L-HRP admin.) in the AM epileptogenic focus (2 of 5 animals tested) | 71 |
| / | LPs (PC:CHOL:Sterylamine 7:2:1) | DN-1417 | Amygdaloid kindled rats | Anticonvulsivant effect | Suppression of kindled seizure and prolonged anticonvulsivant effect after L-DN 1417 admin. than free DN 1417 | 70 | |
| / | LPs (cationic) | VPA | Amygdaloid kindled rats | Anticonvulsivant effect | Prolonged anticonvulsivant effect after cationic L-VPA admin (2 days) than anionic L-VPA admin and free VPA (1 h) | 72 | |
| LDL Receptor | PBCA-NPs-Ps80 | MRZ 2/576 | Convulsion model in mice | Anticonvulsivant effect (MES test) | Longer duration in MES test after coated Np-MRZ 2/576 admin. (up to 210 min) than uncoated Np admin. (60 min) | 36 | |
| Lysosomal storage disorders | Transferrin receptor (BBB) | LPs (POPC: DDAB : DSPE-PEG2000: DSPE-PEG2000-maleimide + 8D3 mAb) | pCMV-GUSB plasmid DNA | MPS type VII GUSB null mice | GUSB enzyme activity measurement Protein concentration determination | GUSB enzyme activity in the brain of adult mice = 13.3 ± 0.9 nmol/hr/mg protein; GUSB enzyme activity in the brain of GUSB null mice after L/plasmid DNA treatment =1.7± 0.1 nmol/hr/mg protein; GUSB enzyme activity in the brain of GUSB null mice after saline admin. < 0.2 nmol/hr/mg protein. | 132 |
| Cerebral Ischemia (Traumatic Injury) | / | LPs (DPPC:CHOL: Sterilamine 14:7:4) | CuZn-SOD | Rats cold- injury brain model (Chan et al 1983) | Determination of CuZn-SOD; determination of superoxide radicals; Evans Blue Permeability (BBB permeability) | Protection of drug; increase of CuZn-SOD brain level 8from 30 min to 2 h); reduction in brain level of superoxide radicals and water content and ameliorated BBB permeability | Chan et al 1987 |
| / | LPs (PC:CHOL:Sulfatides) | Calpain inhibitor (ALL NA1) | Gerbil model of forebrain ischemia (Yokota et al 1995) | Immunohistochemistry and immunoblot analysis | Dose dependent prevention after L-ALL Na1of CA1 neuronal damage | Yokota et al., 1999 | |
| / | LPs (DPPC:CHOL: Sterilamine 14:7:4) | CuZn-SOD | Rats model of focal cerebral ischemia (Chen et al.,1986) | CuZn-SOD activity and measure of infarct size | Increase of CuZn-SOD activities in the brain; reduction of infarct size (33%, 25% and 18% for the anterior, middle and posterior slices, respectively) | 49 | |
| / | NPs | MRZ 2/566 | Rats models of focal cerebral ischemia | Quantification of infarct lesion and neurological severity score | Increased neurological score vs placebo Reduction at 53%of total infarct size (60% of cortical and 42% of striatal infarction) | 111 | |
| / | PLGA-NPs | SOD | Rats models of focal cerebral ischemia -perfusion injury model | Quantification of infarct lesion and neurological severity score | 5% of survival after SOD-Np admin. at 28 d (Infarct volume after SOD-Np = 20%, saline control=56%, SOD- SOL=75%. Ischemic lesion area after SOD-Np=25%, saline control =50%, SOD-SOL =80%. Neurological severity score after SOD-Np=3.5, saline control=10, SOD-SOL=11) | 90 | |
| / | PLA-NPs | QC | Rats model of cerebral ischemia | Diene level, index of lipid peroxidation and GSSG/GSH ratio | Significant protection to endogenous antioxidant enzymes against ischemia induced oxidative damage in neuronal cells | 29 | |
| Arsenic induced oxidative damage | / | PLGA-NPs | QC | Rats with neuronal cell damage after NaASO2 injection | Intracellular GSH, GPx, GR, GST and G6PDH activity in the brain | QC-Np prevent the antioxidant deplection in brain cells (levels of GPx from Np 4.98 ± 0.31 vs 2.17±0.09 µmol NADPH oxidation/min/mg protein; G6PDH nmol NADPH reduced/min/mg protein 6.07 ±0.39 vs animal model 3.61 ±0.29; GR µmol NADPH oxidation/min/mg protein 17.92 ±2.33 vs 9.92 ±0.87;GST nmol product/min/mg 97.86 ±7.22 vs 69.26 ±9.88) | 38 |
| Traumatic Brain Injury | / | PANAM dendrimers | N-acetyl-cysteine, valproic acid | Traumatic brain injury, rats | In vivo administration, biodristribution and pharmacological test | PANAM localize in the injured neurons and microglia in the brain. -loading with N-acetyl cysteine and valproic acid | 69 |
| / | self-assembling peptide nanofiber scaffold | / | Traumatic brain injury, rats | In vivo administration | Reduction of acute brain injury and brain cavity formation | 96 | |
| / | pegylated PLGA NP (100-200-800 nm) | / | Traumatic brain injury animal model | In vivo administration, brain localization | Smaller NPs are facilitated in BBB crossing | 25 | |
| / | PLGA NPs | Cerebrolysin | Traumatic brain injury, rats | In vivo administration, brain edema formation, rescue tests | Ability in delivering cerebrolysin to site of action; - reduction of brain pathology features | 94 | |
| Infectious diseases | / | LPs (PC:CHOL:DSPG-AmBisome) | AMB | Candida Albicans infected rabbits | CFU in the brain tissue | Reduction of infection in the brain | 41 |
| / | LPs (PC:CHOL:DSPG-AmBisome) | AMB | Murine model of cryptococcal meningitis (Cryptococcus neoformans) | CFU in the brain tissue and therapeutic activity | 20 mg/kg and 30 mg/kg of Ambisome were able to clear the yeast from the brains of the mice (44 and 78% clearance, respectively) | 5 | |
| / | LPs (PC:CHOL:DSPG-AmBisome) | AMB | Murine model of cryptococcidiosis (Cryptococcus neoformans) | Therapeutic activity in the brain tissue | 10 mg/kg AmBisome = 5.69±0.38 log10 CFU/brain; 1 mg/kg fungizone = 6.92±0.50 log10 CFU/brain. Ten mg/kg Ambisome=50–60% survival; 1 mg/kg fungizone = 12–30%. | 113 | |
| / | LPs (PC:CHOL:DSPG-AmBisome ) | AMB | Immuno-suppressed rabbits with Coccidioides immitis | CFU in the brain tissue and therapeutic activity | 3x15mg/kg Ambisome for 3 weeks clears the fungus from the brains (3/8 rabbits). None with other treatments. CFU reduction vs control | 23 | |
| / | LPs (PC:CHOL:DSPG-AmBisome) Association with other VCZ, CAS, MICA) | AMB | Murine models of CNS aspergillosis | CFU in the brain tissue and therapeutic activity of animals | 1 mg/kg Ambisome from 1 to 3 d with VCZ from days 4 to 10 demonstrated higher efficacy than other combinations | 22 | |
| LDLr (?) | PLA-b-PEG-NPs-Ps 80 | AMB | Cryptococcal Meningitis Bearing Mice | Fungal growth and therapeutic activity | Survival: twice than controls | 92 | |
| CG3R6TAT NPs | CG3R6TAT | Staphilococcus Aureus induced meningitis rabbit model | CFU in the brain tissue | Np 2 lg CFU/g tissue; control 3.7 lg CFU/g tissue; Suppression of bacterial growth in the brain, decreasing the degree of the infection | 61 | ||
| CG3R6TAT NPs | CG3R6TAT | Criptococcal neoformans meningitis rabbit model | CFU in the brain tissue and biodistribution studies (FITC-loaded Np) | Suppression of yeast growth in brain tissue (Np treatment < 2CFU/g; control ≥15/g). | 121 |
LPs, liposomes; PC, phosphatidylcholine; CHOL, cholesterol; PHT, phenytoin; HRP, horseradish peroxidase; AM, amygdala; DN-1417, γ -butyrolactone- γ-carbonyl-L-histidyl-Lpropinamide citrate; VPA, valproic acid; PBCA, poly(butylcyanoacrylate); NPs, nanoparticles; MRZ 2/576, 8-chloro-4-hydroxy-1-oxo-1,2-dihydropyridazino[4,5-b]quinoline-5-oxide choline salt; MES, prevention of maximal electroshock; POPC, 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine; DDAB, dimethyldioctadecylammonium bromide; DSPE-PEG2000 distearoylphosphatidylethanolamine polyethylene glycol; 8D3 mAb, monoclonal antibody against the mouse transferring receptor; ; GUSB, b-glucuronidase; MPS, mucopolysaccharidosis; CuZn-SOD, CuZn superoxidase dismutase; DPPC, dipalmitoyl phosphatidylcholine; DPPS dipalmitoyl phosphatidylserine; MRZ 2/566, (8-chloro-4-hydroxy-l-oxo- 1,2-dihydropyridazino[4,5-b]quinolin-5-oxide choline salt; PANAM, polyamidoamine; PLGA, poly(D,L-lactide co-glycolide); SOD, superoxide dismutase; QC, Quercetin; GSSG, oxidized glutathione; GSH, reduced glutathione; PLA, Polylactide; NaASO2, sodium arsenite; GSH, glutathione; GPx, glutathiane peroxidase; GR, glutathione reductase; GST, glutathione-S-transferase; G6PDH, glucose-6-phosphate dehydrogenase; NADPH, nicotinamide adenine dinucleotide phosphate-oxidase; DSPG, distearoylphosphatidylglycerol; CFU, colony forming units; VCZ, voriconazole; CAS, caspofungin; MICA, micofungin; Ps80, Polysorbate 80; AMB, amphotericin B; CG3R6TAT, cholesterol conjugated 3 glycine, six arginine and TAT peptide; FITC, fluorescein isothiocyanate.