Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles

Nishu Dixit, Kumar Vaibhav, Ravi Shankar Pandey, Upendra Kumar Jain, Om Prakash Katare, Anju Katyal, Jitender Madan

Research output: Contribution to journalArticle

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Abstract

Purpose: Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results: Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH~5.6 (cervical cancer pH) and pH~7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion: Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalBiomedicine and Pharmacotherapy
Volume69
DOIs
StatePublished - Feb 1 2015
Externally publishedYes

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Gelatin
Folic Acid
Uterine Cervical Neoplasms
Nanoparticles
Cisplatin
HeLa Cells
Tissue Distribution
Fourier Transform Infrared Spectroscopy
Endocytosis
Cell Nucleus
Particle Size
Inhibitory Concentration 50
Lung Neoplasms
Analysis of Variance
Cytoplasm
Apoptosis
Ligands
Technology
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Cellular uptake
  • Cervical cancer
  • Cisplatin
  • Cytotoxicity
  • Folate
  • Gelatin nanoparticles

ASJC Scopus subject areas

  • Pharmacology

Cite this

Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles. / Dixit, Nishu; Vaibhav, Kumar; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katare, Om Prakash; Katyal, Anju; Madan, Jitender.

In: Biomedicine and Pharmacotherapy, Vol. 69, 01.02.2015, p. 1-10.

Research output: Contribution to journalArticle

Dixit, Nishu ; Vaibhav, Kumar ; Pandey, Ravi Shankar ; Jain, Upendra Kumar ; Katare, Om Prakash ; Katyal, Anju ; Madan, Jitender. / Improved cisplatin delivery in cervical cancer cells by utilizing folate-grafted non-aggregated gelatin nanoparticles. In: Biomedicine and Pharmacotherapy. 2015 ; Vol. 69. pp. 1-10.
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AU - Jain, Upendra Kumar

AU - Katare, Om Prakash

AU - Katyal, Anju

AU - Madan, Jitender

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N2 - Purpose: Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results: Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH~5.6 (cervical cancer pH) and pH~7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion: Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.

AB - Purpose: Cisplatin is highly effective in the treatment of cervical cancer. However, in therapeutic doses, cisplatin induces several adverse effects due to undesirable tissue distribution. Therefore, it is worth targeting cisplatin in cervical cancer cells by implicating non-aggregated ligand-modified nanotherapeutics. Methods and results: Here, we report the preparation of non-aggregated folic acid-conjugated gelatin nanoparticles of cisplatin (Cis-GNs-FA) by two-step desolvation method with mean particle size of 210.6±9.6nm and 140.5±10.9nm for Cis-GNs to improve the drug delivery in cervical cancer, HeLa cells. FTIR and DSC spectra confirmed the presence and stability of cisplatin in gelatin matrix. Furthermore, amorphization of cisplatin in nanoparticles was ascertained by PXRD. Drug release followed a first-order release kinetic at both pH~5.6 (cervical cancer pH) and pH~7.4. In addition, a significant (P<0.05) decrease in IC50 value (8.3μM) and enhanced apoptosis were observed in HeLa cells treated with Cis-GNs-FA as compared to Cis-GNs (15.1μM) and cisplatin solution (40.2μM). In contrast, A549 lung cancer cells did not discriminate between Cis-GNs-FA and Cis-GNs due to the absence of folate receptors-α (FR-α). Consistently, higher cellular uptake, 80.54±7.60% was promoted by Cis-GNs-FA significantly (two-way ANOVA, P<0.05) greater than 51.68±9.78%, by Cis-GNs. This was also illustrated by CLSM images, which indicated that Cis-GNs-FA preferably accumulated in the cytoplasm of HeLa cells nearby nucleus by following receptor-mediated endocytosis pathway as compared to Cis-GNs. Conclusion: Therefore, Cis-GNs-FA warrants further in-depth in vitro and in vivo investigations to scale up the technology for clinical translation.

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