Sapataparna Dasgupta, Bennett University
Little study has been done on nanoparticles as biocompatible drug delivery carriers. Cancer, being the most lethal disease and the greatest cause of death worldwide, emerges as the most researched disease in the current scenario. Amongst cancer, breast cancer stands to be the leading cause of death for women all over the world as per the reports of WHO 2018. Thus, chemotherapy emerged as a leading conventional therapy, for the treatment of various stages of cancer. Antineoplastic drugs pose opposite to drug resistance and bring out the effectiveness of the drug better for the treatment purpose. These drugs with various mechanisms are combined in diverse ways to produce a synergistic effect. Certain drugs like Doxorubicin and Epoxomicin were used for chemotherapy for the treatment of various types of cancer.
Doxorubicin and Epoxomicin loaded Nanoparticles:
Doxorubicin (Dox) is an antineoplastic drug, a broad-spectrum antibiotic drug, used for the treatment of cancerous tumours. To combat the Doxorubicin-induced side effects, the nanoparticles have been examined and have offered great potential for better and safer options for drug delivery. Epoxomicin (Epo), being a natural selective proteasome inhibitor and exhibiting anti-inflammatory effect, have been proven to be of great use in therapeutics for cancer. Due to various synergistic therapeutic impact, co-administration of Epo with powerful Dox can lessen the adverse effects of Dox on normal tissues and result in a reduction in the amount of Doxorubicin and other anticancer medicines required.
The Study
As the nanoparticles have already proved their potential for delivering drugs within the cells due to high biocompatibility and are potent for the targeted drug delivery mechanism in breast cancer. The research, containing the drug combination of more than two antitumor mechanisms. Currently, polymeric-based nanoparticles have received a lot of attention because of their biodegradability and lack of cytotoxicity. PLGA, or poly(lactic-co-glycolic acid), is a biocompatible polymer that can be used for the encapsulation of hydrophobic medicines and therefore elevating the drug plasma retention time of the drug. For this study, Dox and Epo were encapsulated in PLGA, based on the fabrication of nanoparticles via the multiple emulsion technique for solvent evaporation. The categorization of the nanoparticles as biocompatible drug delivery carriers was done based on the size of the particle to be adsorbed, stability, encapsulation efficiency, morphological characteristics of the surface, and the in vitro drug-releasing properties. Moreover, the demonstration of the effect of the synthesized nanoparticles as biocompatible drug delivery carriers on the cells, and the apoptotic effect in turn produced by it on the tumour cells was conducted.
Fig. The mode of adsorption of the chemotherapeutic drug on PLGA fabricated nanoparticle (Created in biorender.com)
The Observed Results
Based on the analysis, the size of the nanoparticles was much reduced when unloaded, while on the other hand, it was observed to increase, when loaded with Doc or Epo. This way, the sample adsorption on the nanoparticles was observed for clinical applications. Also, the zeta potential was observed to increase upon sample loading on nanoparticles. Analyzing the surface topology, when observed under a scanning electron microscope, structural change was revealed, in terms of size or shape from unloaded to loaded with Dox or Epo. Detection of the intermolecular interactions revealed lower peak characteristics in the graph when the PLGA based nanoparticles were loaded with Dox or Epo. Depending on the thermal characteristics the graph peaks were observed to be low when unloaded as compared to the endothermic peaks of the loaded samples with Dox or Epo. The efficiency of the encapsulation of the drugs on the nanoparticles was observed to be slightly better for Epo than Dox.
Acquired Conclusion
Celecoxib (CXB), a selective COX-2 inhibitor, is known to enhance the cytotoxicity level for Dox in breast cancer cells that overexpress P-GP. Hence, Dox along with CXB is known to overcome the problem of drug resistance in the apoptosis of cancer cells. Drugs, playing a role as an inhibitor of Nuclear Factor- kappa B (NF-κB) have been reported to decrease the drug resistivity and increase the apoptotic properties of the drugs, Dox and Epo respectively. It was derived that the reduction of the P-GP levels was possible upon the suppression of the NF-κB in Dox as a chemotherapeutic drug. It was, therefore, proved that Dox and Epo both combined have been successful in overcoming the drug resistance by repressing the activation of NF-κB. This thereby promotes apoptosis in breast cancer without having any adverse effects on the normal cells, through the nanoparticles as biocompatible drug delivery carriers.
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Source: Kucuksayan, E., Bozkurt, F., Yilmaz, M.T. et al. A new combination strategy to enhance apoptosis in cancer cells by using nanoparticles as biocompatible drug delivery carriers. Sci Rep11, 13027 (2021). https://doi.org/10.1038/s41598-021-92447-x
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About the Author: Saptaparna Dasgupta, currently a B. Tech 3rd year student, pursuing Biotechnology, is a diligent student and determined in terms of her career goals. Being a budding biotechnologist, she is open to all research fields of her course and passionate about knowledge. She is focused and constantly tries to improve her writing skills, also a project enthusiast and is fond of gaining hands-on experience in laboratories. Being a Bengal resident, she believes that hard work and efforts together pay off eventually and she follows this as the motto of her life.
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