Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells

Kevin O. Affram, Taylor Smith, Edward Ofori, Sunil Krishnan, Patrick Underwood, Jose G. Trevino, Edward Agyare

Research output: Contribution to journalArticle

Abstract

This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2 pancreatic cancer cells. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Cytotoxic effect of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) = 27 ± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) = 126 ± 3 μM; IC50 (3D) = 241 ± 3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) = 56 ± 16 μM; IC50 (3D) = 127 ± 4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) = 188 ± 46 μM; IC50 (3D) = 254 ± 52 μM). Overall, Gem-SLN15 proved to be more effective against PPCL_46 and Mia-PaCa-2 cells than GemHCl treated PPCL-46 and Mia-PaCa-2 cancer cells.

Original languageEnglish (US)
Article number101374
JournalJournal of Drug Delivery Science and Technology
Volume55
DOIs
StatePublished - Feb 2020

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gemcitabine
Pancreatic Neoplasms
Nanoparticles
Inhibitory Concentration 50
Lipids
Polysorbates
Poloxamer
Differential Scanning Calorimetry
Fourier Analysis
Thermodynamics
Particle Size
Surface-Active Agents
Spectrum Analysis

Keywords

  • Gemcitabine
  • In-vitro release kinetics
  • Primary pancreatic cancer
  • Solid lipid nanoparticle
  • Spheroids

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells. / Affram, Kevin O.; Smith, Taylor; Ofori, Edward; Krishnan, Sunil; Underwood, Patrick; Trevino, Jose G.; Agyare, Edward.

In: Journal of Drug Delivery Science and Technology, Vol. 55, 101374, 02.2020.

Research output: Contribution to journalArticle

Affram, Kevin O. ; Smith, Taylor ; Ofori, Edward ; Krishnan, Sunil ; Underwood, Patrick ; Trevino, Jose G. ; Agyare, Edward. / Cytotoxic effects of gemcitabine-loaded solid lipid nanoparticles in pancreatic cancer cells. In: Journal of Drug Delivery Science and Technology. 2020 ; Vol. 55.
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abstract = "This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2 pancreatic cancer cells. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween{\circledR} 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Cytotoxic effect of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) = 27 ± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) = 126 ± 3 μM; IC50 (3D) = 241 ± 3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) = 56 ± 16 μM; IC50 (3D) = 127 ± 4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) = 188 ± 46 μM; IC50 (3D) = 254 ± 52 μM). Overall, Gem-SLN15 proved to be more effective against PPCL_46 and Mia-PaCa-2 cells than GemHCl treated PPCL-46 and Mia-PaCa-2 cancer cells.",
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AU - Affram, Kevin O.

AU - Smith, Taylor

AU - Ofori, Edward

AU - Krishnan, Sunil

AU - Underwood, Patrick

AU - Trevino, Jose G.

AU - Agyare, Edward

PY - 2020/2

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N2 - This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2 pancreatic cancer cells. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Cytotoxic effect of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) = 27 ± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) = 126 ± 3 μM; IC50 (3D) = 241 ± 3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) = 56 ± 16 μM; IC50 (3D) = 127 ± 4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) = 188 ± 46 μM; IC50 (3D) = 254 ± 52 μM). Overall, Gem-SLN15 proved to be more effective against PPCL_46 and Mia-PaCa-2 cells than GemHCl treated PPCL-46 and Mia-PaCa-2 cancer cells.

AB - This study investigated the cytotoxic effects of gemcitabine-loaded solid lipid nanoparticle (Gem-SLN) on the patient-derived primary pancreatic cancer cell lines (PPCL-46) and MiaPaCa-2 pancreatic cancer cells. Different SLN formulations were prepared from glyceryl monostearate (GMS), polysorbate 80 (Tween® 80) and poloxamer 188 (Pol 188) as surfactants using a cold homogenization method. Gem-SLN was characterized for particle size and charge distribution, entrapment efficiency and loading capacity. Fourier Transform Infra-Red (FTIR) spectroscopy was used to verify Gem and SLN interaction while differential scanning calorimetry (DSC) was used to acquire thermodynamic information on Gem-SLN. Cytotoxicity studies was conducted on PPCL-46 cells and Mia-PaCa-2 cells. Among the different Gem-SLN formulations prepared, Gem-SLN15 was selected based on entrapment efficiency (EE) of Gem, loading efficiency of Gem, cytotoxicity and rate of Gem release. Cytotoxic effect of Gem-SLN15-treated PPCL-46 culture (IC50 (2D) = 27 ± 5 μM; IC50 (3D) = 66 ± 2 μM) was remarkably higher than gemcitabine hydrochloride (GemHCl)-treated PPCL-46 culture (IC50 (2D) = 126 ± 3 μM; IC50 (3D) = 241 ± 3 μM). Similar trend of higher Gem-SLN15 inhibition in MiaPaCa-2 culture was found (IC50 (2D) = 56 ± 16 μM; IC50 (3D) = 127 ± 4 μM) compared with GemHCl-treated Mia-PaCa-2 culture (IC50 (2D) = 188 ± 46 μM; IC50 (3D) = 254 ± 52 μM). Overall, Gem-SLN15 proved to be more effective against PPCL_46 and Mia-PaCa-2 cells than GemHCl treated PPCL-46 and Mia-PaCa-2 cancer cells.

KW - Gemcitabine

KW - In-vitro release kinetics

KW - Primary pancreatic cancer

KW - Solid lipid nanoparticle

KW - Spheroids

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