Introduction
Dendrimers are highly branched polymeric molecules. Structural perfection is the most important feature of dendrimers, and other chemical substances can be conjugated with dendrimers and used for therapeutic applications. Chemically conjugated dendrimers can be used as affinity ligands, dye-detecting agents, radioligands, targeting components, and active pharmaceutical compounds. Poly (propylene imine) glycodendrimers (PPI) are popular drug carriers. They are used in the treatment of neurodegenerative diseases and cancer. Neurotoxicity depends on the dose of poly (propylene imine) dendrimers (PPI).
What Are Dendrimers?
Dendrimers are branched organic compounds which possess terminal functional groups on the surface. Terminal functional groups present on the surface of dendrimers can be modified to enhance the functional properties of dendrimers. Chemically modified dendrimers can be made biocompatible to produce various pharmaceutical products for therapeutic uses. Because of their unique properties like water solubility, high reactivity, nanoscale size, internal cavities, globular shape, and comfortable synthesis methods, dendrimers are used for nanomedicine applications. The main therapeutic application of dendrimers is as drug delivery agents. In addition, they can be used as drug carriers to increase drug efficacy and reduce toxicity.
The different types of dendrimers used for therapeutic use are as follows.
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Poly (aminoamide) or PAMAM dendrimer.
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Poly (propylene imine) or PPI dendrimer.
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Chiral dendrimer.
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Tecto dendrimer.
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Hybrid dendrimer.
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Peptide dendrimer.
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Multilingual dendrimer.
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Amphiphilic dendrimer.
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Frechet types dendrimer.
What Are Poly (Propylene Imine) Glycodendrimers?
Poly (propylene imine) dendrimers (PPI) and poly (amidoamine) dendrimers (PAMAM) are important dendrimers used in nanomedicine. The outer surface of these dendrimers can be modified and coupled with ligands and tumor markers to facilitate targeted delivery of the drug molecules to the specific site. A dendrimer is coated with sugar (monosaccharides, trisaccharides, and disaccharides) to form glycodendrimers. Poly (propylene imine) dendrimers (PPI) are majorly used for therapeutic applications related to neoplastic diseases and chromosomal or genetic aberrations (chronic B-cell lymphoproliferative diseases). These dendrimers belong to third, fourth, and fifth-generation dendrimers. Dendrimers are surface modified with sugar molecules to form Poly (propylene imine) glycodendrimers. Sugar molecules that are used to modify the dendrimer are mannose or lactose.
What Are the Therapeutic Applications of Poly (Propylene Imine) Glycodendrimers?
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Cancer Targeting Potential - Poly (propylene Imine) glycodendrimers can be used to deliver anticancer drugs to the target neoplastic tissues. It can be done in conjugation with other therapeutic drugs or in free form. Targeted drug delivery using poly (propylene imine) glycodendrimers have shown promising results. They increase the effectiveness of antineoplastic drugs through controlled release and gene transfection efficiency, improve tumor cell penetration, reduce adverse effects, and increase bioavailability. A cancer diagnosis can be achieved by coupling cancer biomarkers and poly (propylene Imine) glycodendrimers. Thus it will help in the early detection of malignant changes in the cells and cancer treatment.
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Biosensors - Poly (propylene imine) glycodendrimers are a nanowire in sensor fabrication. Numerous functional groups on the large surface of dendrimers will help bind biologically active molecules. Poly (propylene imine) glycodendrimers are used to produce immune -biosensors, and nano-mediators.
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Alzheimer's Disease - It is a complex neurological disease characterized by remarkable memory loss. It occurs due to synaptic dysfunction and deficiency of neurotransmitters. Before the onset of synaptic damage, there will be a presymptomatic phase in Alzheimer's disease. The presymptomatic phase occurs before the initiation of neuronal loss and synaptic damage. Therapeutic management of Alzheimer's disease is most effective in the presymptomatic phase. Preventive treatment using poly (propylene imine) glycodendrimers will protect the synaptic damage and prevent the development of Alzheimer's disease. Dendrimers are modified with anti-amyloidogenic agents like maltose and chelating agents like histidine to improve pharmaceutical actions and reduce synaptic damage. Poly (propylene imine) glycodendrimers are modified with histidine and maltose to possess neuroprotective and anti-amyloid properties.
What Are the Toxic Effects Associated With Poly (Propylene Imine) Glycodendrimers?
Even though dendrimers possess various advanced biological applications, they can induce toxic effects in body tissues. The toxicity of dendrimers can be reduced by coating them with carbohydrate molecules. Compared to non-conjugated dendrimers, poly (propylene imine) glycodendrimers have less toxic effects.
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Cytotoxicity - It is an important adverse effect associated with the biological application of poly (propylene imine) glycodendrimers. Cytotoxicity associated with dendrimers depends on the generation of the dendrimer, the nature of the terminal groups (neutral, cationic, anionic), and the number of surface groups present. Higher cytotoxicity is observed in dendrimers with a positive surface charge, which belongs to the higher generation. Chemical modification with carbohydrates, acetyl groups, polyethylene glycol (PEG), and other moieties shows reduced cytotoxicity.
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Neurotoxicity - Neurotoxicity - Poly (propylene imine) glycodendrimers are used as therapeutic agents for the treatment of neurodegenerative diseases and brain tumors. These molecules can cross the blood-brain barrier and induce pharmacological effects in the brain cells. Studies have shown that based on the dosage, toxic effects are observed in the brain cells after the use of dendrimers. The toxic effects induced by dendrimers in the nervous system will accumulate over time. The neurotoxic effects of poly (propylene imine) glycodendrimers occur due to nanoparticle-induced autophagy. Autophagy is a natural event in human cells that regulates unnecessary and dysfunctional cells in our body. Nanotoxicity after using poly (propylene imine) glycodendrimers will lead to autophagy. It occurs due to the normal defense mechanism of our body against toxic substances present in the cells. Poly (propylene imine) glycodendrimers induced neurotoxicity will result in neural cell damage and altered nervous system function.
Conclusion
Poly (propylene imine) glycodendrimers are highly branched polymeric molecules used as potential drug carriers. They help to increase the drug's effectiveness and bioavailability by targeted action on body cells. Never developments in nanotechnology have increased the use of dendrimers as therapeutic agents. Neurotoxicity is observed with the increased use of poly (propylene imine) glycodendrimers as drug-delivering agents for the management of neurodevelopmental disorders, malignancies, and Alzheimer's disease.
