Abuse-deterrent properties and cytotoxicity of poly(ethylene oxide) after thermal tampering

Babanejad, Niloofar; Kandalam, Umadevi; Ahmad, Rand; Omidi, Yadollah; Omidian, Hossein

doi:10.1016/j.ijpharm.2021.120481

Cited by 4 publications

(4 citation statements)

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“…In addition, cell viability on Gelatin-Ph nanofiber mats obtained from solutions containing 2 and 4 w / v % PEO was over 90% for 5 days ( Figure 3 b), which indicated that the amount of PEO in the solution did not affect nanofiber-induced cytotoxicity to HEK293 cells. PEO has previously been reported to have no cytotoxicity [ 34 ]. Furthermore, cell density on the nanofiber mats was higher than those on the culture dishes (control) ( Figure 3 c).…”

Section: Resultsmentioning

confidence: 99%

Gelatin-Based Electrospun Nanofibers Cross-Linked Using Horseradish Peroxidase for Plasmid DNA Delivery

2022

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The delivery of nucleic acids is indispensable for tissue engineering and gene therapy. However, the current approaches involving DNA/RNA delivery by systemic and local injections face issues such as clearance, off-target distribution, and tissue damage. In this study, we report plasmid DNA (pDNA) delivery using gelatin electrospun nanofibers obtained through horseradish peroxidase (HRP)-mediated insolubilization. The nanofibers were obtained through the electrospinning of an aqueous solution containing gelatin possessing phenolic hydroxyl (Ph) moieties (Gelatin-Ph) and HRP with subsequent HRP-mediated cross-linking of the Ph moieties by exposure to air containing 16 ppm H2O2 for 30 min. Then, Lipofectamine/pDNA complexes were immobilized on the nanofibers through immersion in the solution containing the pDNA complexes, resulting in transfection and sustained delivery of pDNA. Cells cultured on the resultant nanofibers expressed genome-editing molecules including Cas9 protein and guide RNA (gRNA), resulting in targeted gene knock-in and knock-out. These results demonstrated the potential of Gelatin-Ph nanofibers obtained through electrospinning and subsequent HRP-mediated cross-linking for gene therapy and tissue regeneration by genome editing.

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Section: Resultsmentioning

confidence: 99%

Gelatin-Based Electrospun Nanofibers Cross-Linked Using Horseradish Peroxidase for Plasmid DNA Delivery

2022

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“…These samples were used in the evaluation of the heat effect on, (i) the PEO structural changes using FTIR spectrometer (Spectrum 100 FTIR, PerkinElmer, Shelton, CT, USA) and Differential Scanning Calorimetry, DSC 4000 (PerkinElmer, the Netherlands), (ii) the PEO rheological changes using a Cone & Plate Rheometer (Brookfield DV-III Ultra, Middleboro, MA, USA; 2.4 cm cone), (iii) the syringeability using a Texture Analyzer, Brookfield CT3 (Brookfield, Middleboro, MA, USA), To compare the results of this study with those we have published on low molecular weight PEO, we used same methodology as previously reported. 5 Results and Discussion Fig. 1A shows the FTIR spectra of the control and heat-treated samples.…”

Section: Methodsmentioning

confidence: 99%

“…The GMSC and MG63 cell viability of control, 80ºCtreated and 180ºC-treated low molecular weight PEO 5 were statistically compared with the GMSC and MG63 cell viability of control, 80ºC-treated and 180ºC-treated high molecular weight PEO, respectively. Table 2 demonstrates these comparisons for the GMSC and MG63 cells.…”

Section: Effect Of Peo Molecular Weightmentioning

confidence: 99%

“…This can be attributed to the excellent film-forming capability of low molecular weight PEO that enhances the adhesiveness as well as the integrity of the tablet composition. 5,6 When an oral ADF no longer offers the same euphoric feeling, abusers may manipulate the formulation to achieve a greater or faster euphoria. 6 Thermal manipulation is one of the major tools used by abusers to overcome crush resistance and extraction resistance of drug products.…”

Section: Introductionmentioning

confidence: 99%

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Functional properties of thermally tampered poly(ethylene oxide)

et al. 2022

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Introduction: Poly(ethylene oxide) (PEO) is the most common polymer used in commercial abuse-deterrent tablets. Due to its vulnerability to high-temperature manipulation, we investigated abuse-deterrent capability and the toxicity of this polymer upon thermal treatments at 80°C and 180°C for 1 hour. Methods: Tablets (200 mg PEO and 300 mg Avicel®) were directly compressed under 2000 lb. The thermally manipulated PEOs were evaluated for their viscosity, crushability, structural changes, and cell toxicity. Results: Our findings showed that 180°C-treated tablets underwent some degrees of oxidative degradation with profound toxicity in both mesenchymal stem cells and MG63 cells. The 180°C-treated tablets exhibited almost no resistance against crushing and were prone to abuse. While thermal processing of PEO at around its melting temperature is a common approach to enhance crush resistance of its dosage forms, thermal manipulation at close to the PEO’s oxidation temperature can lead to structural changes, dramatic loss of crush and extraction resistance, and significant cell toxicity. Conclusion: Similar to the low molecular weight PEO, when thermally manipulated at its thermo-oxidative temperature, the high molecular weight PEO loses its deterrence performance and causes severe cell toxicity.

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