TY - JOUR
T1 - Nanoparticles of cisplatin augment drug accumulations and inhibit multidrug resistance transporters in human glioblastoma cells
AU - Maliyakkal, Naseer
AU - Appadath Beeran, Asmy
AU - Udupa, Nayanabhirama
N1 - Funding Information:
The authors extend their appreciation to the Deanship of Scientific Research (DSR) at King Khalid University (KKU), Abha, Kingdom of Saudi Arabia, for funding this work through the General Research Project under the grant number G.R.P-333-39. We would like to acknowledge Dr. Devaveena Dey (Assistant Professor, USU Walter Reed Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD, USA) for technical editing, reviewing, and revising the manuscript. The authors also acknowledge Dr. Gopal Shavi (Principal Professional, LEO Pharma A/S, Crumlin Dublin, Ireland) and Dr. Praful Deshpande (Lead Scientist, Teva Pharmaceuticals, Waterford Metropolitan Area, Ireland) for their help with formulation and development.
Funding Information:
The authors extend their appreciation to the Deanship of Scientific Research (DSR) at King Khalid University (KKU), Abha, Kingdom of Saudi Arabia, for funding this work through the General Research Project under the grant number G.R.P-333-39.
Publisher Copyright:
© 2021 The Authors
PY - 2021/8
Y1 - 2021/8
N2 - Background: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP's clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting of cisplatin in GBM via cisplatin loaded polymeric nanoplatforms (CSP-NPs). Methods: CSP-NPs were prepared by modified double emulsion and nanoprecipitation techniques. The physiochemical characterizations of CSP-NPs were performed using zeta sizer, scanning electron microscopy (SEM), drug release kinetics, and drug content analysis. Cytotoxicity, induction of apoptosis, and cell cycle-specific activity of CSP-NPs in human GBM cell lines were evaluated by MTT assay, fluorescent microscopy, and flow cytometry. Intracellular drug uptake was gauged by fluorescent imaging and flow cytometry. The potential of CSP-NPs to inhibit MDR transporters were assessed by flow cytometry-based drug efflux assays. Results: CSP-NPs have smooth surface properties with discrete particle size with required zeta potential, polydispersity index, drug entrapment efficiency, and drug content. CSP-NPs has demonstrated an ‘initial burst effect’ followed by sustained drug release properties. CSP-NPs imparted dose and time-dependent cytotoxicity and triggered apoptosis in human GBM cells. Interestingly, CSP-NPs significantly increased uptake, internalization, and accumulations of anticancer drugs. Moreover, CSP-NPs significantly reversed the MDR transporters (ABCB1 and ABCG2) in human GBM cells. Conclusion: The nanoparticulate system of cisplatin seems to has a promising potential for active targeting of cisplatin as an effective and specific therapeutic for human GBM, thus eliminating current chemotherapy's limitations.
AB - Background: Cisplatin (CSP) is a potent anticancer drug widely used in treating glioblastoma multiforme (GBM). However, CSP's clinical efficacy in GBM contrasted with low therapeutic ratio, toxicity, and multidrug resistance (MDR). Therefore, we have developed a system for the active targeting of cisplatin in GBM via cisplatin loaded polymeric nanoplatforms (CSP-NPs). Methods: CSP-NPs were prepared by modified double emulsion and nanoprecipitation techniques. The physiochemical characterizations of CSP-NPs were performed using zeta sizer, scanning electron microscopy (SEM), drug release kinetics, and drug content analysis. Cytotoxicity, induction of apoptosis, and cell cycle-specific activity of CSP-NPs in human GBM cell lines were evaluated by MTT assay, fluorescent microscopy, and flow cytometry. Intracellular drug uptake was gauged by fluorescent imaging and flow cytometry. The potential of CSP-NPs to inhibit MDR transporters were assessed by flow cytometry-based drug efflux assays. Results: CSP-NPs have smooth surface properties with discrete particle size with required zeta potential, polydispersity index, drug entrapment efficiency, and drug content. CSP-NPs has demonstrated an ‘initial burst effect’ followed by sustained drug release properties. CSP-NPs imparted dose and time-dependent cytotoxicity and triggered apoptosis in human GBM cells. Interestingly, CSP-NPs significantly increased uptake, internalization, and accumulations of anticancer drugs. Moreover, CSP-NPs significantly reversed the MDR transporters (ABCB1 and ABCG2) in human GBM cells. Conclusion: The nanoparticulate system of cisplatin seems to has a promising potential for active targeting of cisplatin as an effective and specific therapeutic for human GBM, thus eliminating current chemotherapy's limitations.
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U2 - 10.1016/j.jsps.2021.07.001
DO - 10.1016/j.jsps.2021.07.001
M3 - Article
AN - SCOPUS:85111580503
SN - 1319-0164
VL - 29
SP - 857
EP - 873
JO - Saudi Pharmaceutical Journal
JF - Saudi Pharmaceutical Journal
IS - 8
ER -