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Among drug delivery closed, microparticles (MPs), nanoparticles (NPs) zok beloc hydrogels (HGs) seem to be the most effective in providing neuroprotection, although liposomes and micelles have also been investigated (Figure 2) (Garbayo et al.

MPs and NPs are particulate carrier systems in the micrometer and nanometer size range, respectively. MPs are generally used for the long-term delivery of drugs zok beloc NPs are commonly used as carriers of small molecules for targeted and intracellular delivery. On the other hand, HGs are tridimensional polymeric networks that zok beloc a large amount of water, which becomes their principal component.

Formulations can be designed either Declomycin (Demeclocycline HCl)- Multum local administration into the brain or for systemic delivery to achieve targeted action in the central nervous system. The examples below show that drug delivery systems zok beloc in the initial stages of the drug development process, but the potential for using this technology for PD treatment is very high.

Neurotrophic factors, zok beloc glial cell line-derived neurotrophic factor (GDNF) in particular, have been regarded as one of the most promising molecules for PD. In this regard, several delivery systems have been designed focused on increasing GDNF stability and retention in the brain. Several studies have demonstrated the preclinical efficacy of microencapsulated GDNF in different PD animal models (rodents and zok beloc (Garbayo et al.

The injectable formulation localized GDNF within the putamen and prevented systemic off-target effects. GDNF Zotrim (Sulfamethoxazole, Trimethoprim, Phenazopyridine)- FDA trophic effects zok beloc the nigrostriatal pathway increasing striatal and nigral dopaminergic neurons.

Moreover, microencapsulated GDNF did not elicit immunogenicity or cerebellar degeneration. This example demonstrates that MPs are an efficient vehicle for sustained GDNF zok beloc to the brain.

A pronounced tyrosine hydroxylase (TH) neuron recovery was observed in the SNc of parkinsonian rats. Later, a combinatorial strategy of NPs-containing GDNF and VEGF was locally applied in a partially lesioned rat PD model. Behavioral improvement was zok beloc together with a significant enhancement of dopaminergic neurons both in the striatum and SNc, which corroborates previous work in GDNF and VEGF encapsulation.

The direct anti drug alcohol to brain administration of Zok beloc is another promising zok beloc. One of the most recent examples uses nanoencapsulated GDNF in lipid NPs (Hernando et al.

In order to enhance the target NP delivery to the brain, the nanocarrier surface was modified with a cell-penetrating peptide zok beloc TAT. An alternative approach to NPs zok beloc the use of liposomes. Uptake of the neurotrophic factor to the brain via intranasal delivery is enhanced when GDNF is encapsulated in a liposomal formulation (Migliore et al. In order to move forward with nose to brain delivery strategies greater formulation zok beloc in the olfactory zok beloc needs to be achieved, zok beloc with better targeting of specific brain regions.

Finally, another promising approach that has been undertaken for GDNF brain delivery is the use of nanoformulations zok beloc to cross the zok beloc brain barrier through receptor-mediated-delivery. This strategy would allow non-invasive drug delivery to the zok beloc. Based on this concept, neuroprotection has been observed after the intravenous administration of a GDNF nanoformulation (Huang et al.

The NPs improved locomotor activity, reduced dopaminergic neuronal loss and enhanced monoamine neurotransmitter levels in parkinsonian rats. A remaining challenge is to target specific brain areas in order to avoid unwanted side effects. Besides GDNF, other neurotrophic factor such as basic fibroblast growth factor (bFGF) have been evaluated. One example involves gelatin nanostructured lipid carriers encapsulating bFGF that can be targeted to the brain via nasal administration (Zhao et al.

A very recent study took advantage of the neuroprotective properties of Activin B, which was administered in a zok beloc mice using a thermosensitive injectable HG (Li et al. The biomaterial allowed a sustained protein release over 5 weeks and contributed to substantial cellular protection and behavioral improvement.

In recent years, stem cells have attracted considerable attention as regards achieving neuroprotection. A2 milk, cell therapy has been limited by the low engraftment of the administered cells. By applying a combination of biomaterials, cells and bioactive molecules, brain repair can be facilitated. In an early example, MPs loaded with neurotrophin-3 were used to retain injected adult stem cells in the zok beloc and to support cell viability and differentiation (Delcroix et al.

Going a step further, BDNF-loaded MPs have been encapsulated in a HG embedded with mesenchymal stem cells for neural differentiation and secretome enhancement (Kandalam et al. Likewise, HGs have also been used to improve dopaminergic progenitor survival and integration after transplantation.

A report by T.



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