Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells

Our plain-English summary of Efficacy of piroxicam plus cisplatin-loaded PLGA nanoparticles in inducing apoptosis in mesothelioma cells, by C. Menale, M.T. Piccolo, I. Favicchia, et al (Pharmaceutical Research, 2015).

The study

• Authors: C. Menale, M.T. Piccolo, I. Favicchia, M.G. Aruta, A. Baldi, C. Nicolucci, V. Barba, D.G. Mita, S. Crispi, N. Diano
• Journal: Pharmaceutical Research
• Published: 2015;32(2):362-74
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Purpose: Combined treatment based on cisplatin-loaded Poly(D,L-lactic-co-glicolic)acid (PLGA) nanoparticles (NP-C) plus the NSAID piroxicam was used as novel treatment for mesothelioma to reduce side effects related to cisplatin toxicity.

Methods: PLGA nanoparticles were prepared by double emulsion solvent evaporation method. Particle size, drug release profile and in vitro cellular uptake were characterized by TEM, DLS, LC/MS and fluorescence microscopy. MSTO-211H cell line was used to analyse NP-C biological efficacy by FACS and protein analysis.

Results: Cisplatin was encapsulated in 197 nm PLGA nanoparticles with 8.2% drug loading efficiency and 47% encapsulation efficiency. Cisplatin delivery from nanoparticles reaches 80% of total encapsulated drug in 14 days following a triphasic trend. PLGA nanoparticles in MSTO-211H cells were localized in the perinuclear space NP-C in combination with piroxicam induced apoptosis using a final cisplatin concentration 1.75 fold less than free drug. Delivered cisplatin cooperated with piroxicam in modulating cell cycle regulators as caspase-3, p53 and p21.

Conclusions: Cisplatin loaded PLGA nanoparticles plus piroxicam showed a good efficacy in exerting cytotoxic activity and inducing the same molecular apoptotic effects of the free drugs. Sustained cisplatin release allowed to use less amount of drug, decreasing toxic side effects. This novel approach could represent a new strategy for mesothelioma treatment.

In plain English

This laboratory study used a human mesothelioma cell line (MSTO-211H), not patients, animals or asbestos. The authors loaded the chemotherapy drug cisplatin into biodegradable PLGA particles about 197 nm across, designed to release it slowly, and tested them alone or with the anti-inflammatory drug piroxicam. In buffer, about 80% of the loaded cisplatin was released over 14 days. Separately, fluorescent-labelled particles entered the cells, mostly around the nucleus. Cell death was reported relative to untreated cells, counted as 0%. At 24 hours, loaded cisplatin plus piroxicam gave 56.3% cell death, against 72.3% for free cisplatin plus piroxicam. At 48 hours the loaded combination gave 87%; the authors called the difference only 10%. Empty particles were not significantly toxic. Both treatments started at 10 μg/ml cisplatin; the authors reasoned that, with 56.6% released by 48 hours, the particles delivered a final concentration 1.75 fold less than the free drug. The loaded combination also triggered apoptosis (programmed cell death). The authors concluded it could be a new mesothelioma treatment strategy, and called for animal studies and early human trials to identify its risks.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (in vitro) experiment: preparation and testing of drug-loaded nanoparticles on a mesothelioma cell line
• Who was studied: The human mesothelioma cell line MSTO-211H, obtained from ATCC and grown in culture. No patients or animals were studied.
• Exposure: No asbestos exposure was studied. Cells were treated for 24 and 48 hours with 10 μg/ml cisplatin, either free or loaded into PLGA nanoparticles, alone or combined with piroxicam 760 μM. Earlier tests also used 5 μg/ml and ran up to 72 hours.
• Main results:
  • The cisplatin-loaded nanoparticles measured about 197 nm. Loading efficiency was 8.2±1.2% and encapsulation efficiency was 47±5.3%.
  • In a release test in phosphate buffered saline (PBS, pH 7.4), about 80% of the loaded cisplatin was released from the nanoparticles after 14 days.
  • Uptake was studied with fluorescent-labelled PLGA nanoparticles (NP-F). These were taken up by the MSTO-211H cells, mostly in the area around the nucleus. Uptake rose until 24 hours, with no further increase at 48 hours.
  • Empty nanoparticles (no drug) caused no significant toxic effects in the cells.
  • At 72 hours, cisplatin-loaded nanoparticles at 5 and 10 μg/ml caused 58.3% and 71% cell death, reported relative to control cells. Free cisplatin had already caused massive cell death by that time.
  • At 24 hours, loaded cisplatin plus piroxicam gave 56.3% cell death and free cisplatin plus piroxicam gave 72.3%. Both values were expressed relative to untreated cells, which were fixed as 0% cell death.
  • At 48 hours, the loaded combination gave 87% cell death relative to untreated cells. The authors described the difference from the free combination as only 10%.
  • Both treatments used a nominal 10 μg/ml cisplatin. Based on 56.6% release from the particles by 48 hours, the authors reasoned that the particles released a final cisplatin concentration 1.75 fold less than the free drug.
  • On Annexin V testing, apoptosis reached 47.6% at 48 hours with loaded cisplatin plus piroxicam. Free cisplatin plus piroxicam reached 50.7% at 24 hours.
  • Loaded cisplatin alone, without piroxicam, did not show a relevant increase in apoptosis on Annexin V testing at 24 or 48 hours.
  • Loaded cisplatin, alone or with piroxicam, did not raise levels of the protein p53. With the loaded combination, the protein p21 moved into the cell nucleus at 24 hours and more so at 48 hours.
• The authors' conclusion: The authors concluded that cisplatin-loaded PLGA nanoparticles plus piroxicam killed mesothelioma cells and produced the same apoptotic effects as the free drugs while using less cisplatin. They said this approach could represent a new strategy for mesothelioma treatment.
• Limitations the authors state:
  • The authors stated that animal studies and phase I/II trials in humans are needed to identify the risks of using nanoparticles and their real clinical impact.
  • The authors noted that knowledge of the negative side effects and possible health toxicities of nanoparticles is insufficient.
  • Combination and apoptosis experiments were not carried out at 72 hours because free cisplatin had already caused massive cell death by then.
  • The authors said further formulations with surface modifications to target mesothelioma cells still need to be developed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cisplatin, Apoptosis, Mesothelioma, Encapsulation.

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