Indian Journal of Pharmacy and Pharmacology

Print ISSN: 2393-9079

Online ISSN: 2393-9087

CODEN : IJPPTK

Indian Journal of Pharmacy and Pharmacology (IJPP) open access, peer-reviewed quarterly journal publishing since 2014 and is published under auspices of the Innovative Education and Scientific Research Foundation (IESRF), aim to uplift researchers, scholars, academicians, and professionals in all academic and scientific disciplines. IESRF is dedicated to the transfer of technology and research by publishing scientific journals, more...


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Bhattacharya and Kuwar: Dendrimer evolution timeline: Ground-breaking progress in cancer treatment


Editorial

Dendrimers can be seen as a bud that will soon flower and have a stronger effect for cancer care.1 The current cancer treatments provide relief, but they can have unfavourable side effects on normal cells. The ability to effectively deliver anti-cancer drugs to the desired area while avoiding harm to normal cells is critical in cancer care. Dendrimers have excellent drug-carrying properties, and their biocompatibility can also be improved. Targeting ligands can be added to the surface of dendrimers for improved cancer cell selectivity, allowing cancer cells to reorganise without damaging healthy cells.2 Dendrimers are a spherical three-dimensional nano-sized strongly branched tree-like architecture. The word dendrimer was derived from the Greek word dendron, which is another name for a tree, since it has the same branching structure as a tree.3 Buhleier et al. succeeded in synthesising a cascade-like repetitive structure of mono and diamine at the periphery of the central core in 1978, and this was the first dendrimer.4 In 1985, Tomalia et al. created a new class of polymer known as starburst macromolecule, in which they synthesised star polymer with excellent structural symmetry, strongly branched and maximum terminal functional density, as well as monodispersed, regulated branching, and reproducibility. Hiroaki et al. created silicone dendrimer in 1990, which is made up of hyperbranched polysiloxanes with silicone hydrogen at the dendrimer's end. The lack of the solvent effect was studied on the dendrimers by the bilayer interaction by Kelly et al. in year 2009. Later in year 2011, the use of dendrimers was done in drug and gene delivery into the cells by Liu et al. In year 2013 Kasturirangan et al had premeditated multifunctional composite nanodevice which was used for cancer therapy and cancer imaging. In year 2014, Jin et al developed commercially available transfection reagent like priofect and superfect that were used to form a stable dendrimer. The rigid structure of dendrimers like polyphenylene dendrimers by studied by Hammer et al in year 2015. Additionally, in year 2016 the linear polymers with higher viscosity than analogue dendritic were studied by Ren et al. To investigate the effect of the form of chemical modification, first- and second-generation dendrimers were synthesised with sulfonic, carboxylic, or phosphonic acids as the polar group and n-propyl, butyl, hexyl, or isopropyl chains as the nonpolar functionality. These chemical modifications were studied by Hammer et al. in year 2017. In year 2018 Zhong developed inhalable pH-sensitive PAMAM dendrimer. Santos et al. discovered that the central core, which is also a dendron, radiates outwards, resulting in a homo-structural layer, in the year 2019. In the year 2020, Huang et al. and Fana et al investigated nanotechnology, which includes various nanomaterials and nanocarriers such as dendrimers, for various applications in medicine and drug delivery to treat serious and lethal diseases such as visceral leishmaniasis, triple negative breast cancer, AIDS, and others. Niu et al. reviewed the applicability of dendrimers with saccharides in their structure in 2021.5 Dendrimers for co-delivery were the subject of the research. Dendrimers are well-known for their special properties, such as monodispersed, which allows them to be replicated at a large scale. The nanoscopic size of dendrimers not only increases surface area but also aids permeation in cells without a barrier. Dendrimer biocompatibility is improved by PEGylation and glycosylation because cationic dendrimers cause cell lysis due to interactions between the cell membrane (negatively charged) and the dendrimer surface (positively charged) that damage the cell membrane.6, 7 According to the World Cancer Report 2020, there were 19.3 million new cancer cases and almost 10.0 million cancer deaths worldwide (excluding nonmelanoma skin cancer).7 Lung cancer, colorectal cancer, breast cancer, and mesothelioma were the cancers with the highest recorded treatment costs. Lung cancer was expected to cost $282,000 over a lifetime, while mesothelioma was estimated to cost $150,000.8 The overall annual economic cost of cancer in 2010 was approximately US$ 1.16 trillion; thus, lowering the cost of promising cancer treatments is expected to be developed in the near future. The current cancer treatment/therapy provides relief, but it also has unfavourable side effects on healthy cells. The ability to effectively deliver anti-cancer drugs to the desired area while avoiding harm to normal cells is critical in cancer care. Liposomes, polymeric nanoparticles, and dendrimers are currently used as drug carriers, with dendrimers having superior properties such as monodispersed, nanoscopic size, multiple functional groups at the periphery, tunable size, reproducibility, and biocompatibility. The tumour has an acidic pH (5–6), while the body system circulation has a neutral to alkaline pH (7.4); this pH discrepancy will be a key factor in designing next-generation stimuli-responsive dendrimer nanocarriers. Dendrimer-based nanocarriers can be used not only for treatment but also for cancer cell detection by encapsulating imaging probes such as fluorescent dye, magnetic resonance imaging contrast, and radionuclide. The majority of the research was done with PAMAM dendrimer, but other dendrimers will be investigated and compared to PAMAM dendrimer in the near future for effective cancer treatment.9 Despite their multifunctional properties, dendrimers have been shown to be toxic to biological membranes due to interactions between the negative charge of the biological membrane and the positive charge of dendrimers, resulting in nanoholes in the membrane. However, researchers have overcome this obstacle by developing biocompatible dendrimers and using dendrimer surface engineering to create nanoholes in the membrane. The perfect medication is Hydrophobic drugs can be encapsulated in the internal voids of biocompatible dendrimers, while hydrophilic drugs can be functionalized at the surface with pH-sensitive hydrolysable linkages. Biomarkers can also be conjugated on top of hydrophilic drugs for identification and attachment at tumour sites.10

Conclusion

Dendrimers have unique properties that make them a promising candidate for a variety of applications. Dendrimers can also help with drug delivery system optimization. Dendrimers may be a breakthrough success for the treatment and diagnosis of various diseases, especially cancer, according to a study that looked at their evolution over nearly four decades. Dendrimers, with their diverse properties, would have a significant effect on future research and offer a more advanced alternative for diagnosis and treatment of multiple cancer.

Source of Funding

None.

Conflict of Interest

None.

References

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J Guerra M A Herrero B Carrion F C P Martínez M Lucío N Rubio Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapyCarbon201250828324410.1016/j.carbon.2012.02.050

2 

A T Kafrani H Shirzadfar E T Kafrani Dendrimers and dendrimers-grafted superparamagnetic iron oxide nanoparticles: synthesis, characterization, functionalization, and biological applications in drug delivery systemsNano Microscale Drug Deliv Syst2017157759410.1016/B978-0-323-52727-9.00005-4

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H Scott M E H El-Sayed El-Sayed, Dendrimers as carriers for delivery of chemotherapeutic agentsChem Rev2009109731415710.1021/cr900174j

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F Vögtle G Richardt N Werner Dendrimer Chemistry: Concepts, Syntheses, Properties, Applications2009354

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L Mousavifar R J M Roy Design, Synthetic Strategies, and Therapeutic Applications of Heterofunctional GlycodendrimersMolecules2021269242810.3390/molecules26092428

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S Beg A Samad M Alam I J C Nazish N D D Targets Dendrimers as Novel Systems for Delivery of Neuropharmaceuticals to the BrainCNS Neurol Disord Drug Formerly Curr Drug Targets CNS Neurol Disord2011105768810.2174/187152711796235023

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J Ferlay M Colombet I Soerjomataram D M Parkin M Piñeros A Znaor Cancer statistics for the year 2020: An overviewInt J Cancer202153381876410.1002/ijc.33588

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O P Badell M Banqué F Macià X Castells M J C E Sala Impact of comorbidity on survival by tumour location: Breast, colorectal and lung cancerCancer Epidemiol200049667410.1016/j.canep.2017.05.010

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M Fana J Gallien B Srinageshwar G L Dunbar PAMAM Dendrimer Nanomolecules Utilized as Drug Delivery Systems for Potential Treatment of Glioblastoma: A Systematic ReviewInt J Nanomedicine 2020152789280810.2147/IJN.S243155

10 

R S Ambekar M Choudhary B J E P J Kandasubramanian Recent advances in dendrimer-based nanoplatform for cancer treatment: A review Eur Polym J2020126510954610.1016/j.eurpolymj.2020.109546



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Article type

Guest Editorial


Article page

179-181


Authors Details

Sankha Bhattacharya, Utkarsha Chhotulal Kuwar


Article History

Received : 05-05-2021

Accepted : 02-08-2021

Available online : 04-09-2021


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