The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts

Ferreira, Luiz Eduardo Nunes; Muniz, Bruno Vilela; Burga-Sánchez, Jonny; Volpato, Maria Cristina; Paula, Eneida de; Rosa, Edvaldo Antônio Ribeiro; Groppo, Francisco Carlos

doi:10.1111/jphp.12680

Cited by 21 publications

(14 citation statements)

References 55 publications

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“…The same amounts of hydrogel (6.25 to 100 mg/mL) free of local anesthetics (CN and C) were diluted and used as placebos. The percentages of viable cells were determined after incubation in the presence of MTT for 3 h at 37 °C, with measurement of the amount of MTT converted to insoluble formazan by mitochondrial dehydrogenases 61,62 . A 100 μL volume of ethanol was added to each well in order to dissolve the formazan crystals, resulting in a purple solution.…”

Section: Methodsmentioning

confidence: 99%

Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia

Muniz

Baratelli

Carla

et al. 2018

Sci Rep

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This study reports the development of nanostructured hydrogels for the sustained release of the eutectic mixture of lidocaine and prilocaine (both at 2.5%) for intraoral topical use. The local anesthetics, free or encapsulated in poly(ε-caprolactone) nanocapsules, were incorporated into CARBOPOL hydrogel. The nanoparticle suspensions were characterized in vitro in terms of particle size, polydispersity, and surface charge, using dynamic light scattering measurements. The nanoparticle concentrations were determined by nanoparticle tracking analysis. Evaluation was made of physicochemical stability, structural features, encapsulation efficiency, and in vitro release kinetics. The CARBOPOL hydrogels were submitted to rheological, accelerated stability, and in vitro release tests, as well as determination of mechanical and mucoadhesive properties, in vitro cytotoxicity towards FGH and HaCaT cells, and in vitro permeation across buccal and palatal mucosa. Anesthetic efficacy was evaluated using Wistar rats. Nanocapsules were successfully developed that presented desirable physicochemical properties and a sustained release profile. The hydrogel formulations were stable for up to 6 months under critical conditions and exhibited non-Newtonian pseudoplastic flows, satisfactory mucoadhesive strength, non-cytotoxicity, and slow permeation across oral mucosa. In vivo assays revealed higher anesthetic efficacy in tail-flick tests, compared to a commercially available product. In conclusion, the proposed hydrogel has potential for provision of effective and longer-lasting superficial anesthesia at oral mucosa during medical and dental procedures. These results open perspectives for future clinical trials.

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Section: Methodsmentioning

confidence: 99%

Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia

Muniz

Baratelli

Carla

et al. 2018

Sci Rep

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“…Cell culture. Immortalized human keratinocytes (HaCaT) were chosen due to their good proliferative capacity in culture and their use in previous in vitro cytotoxicity studies of local anesthetics and drug delivery systems [24,25]. The HaCaT cells (BCRJ 0100, Rio de Janeiro Cell Bank, Rio de Janeiro, RJ, Brazil) were grown in 75 cm 2 TPP 1 bottles (Techno Plastic Products AG, Trasadingen, Switzerland) containing Dulbecco's Modified Eagle Medium (DMEM, Vitrocell, Campinas, SP, Brazil) supplemented with 10% (v/v) fetal bovine serum (Vitrocell), 10,000 U/mL penicillin (Vitrocell), and 100 μg/mL streptomycin (Vitrocell), at 37˚C, in a humid atmosphere with 5% CO 2 [24,25] .…”

Section: In Vitro Modelsmentioning

confidence: 99%

Promising potential of articaine-loaded poly(epsilon-caprolactone) nanocapules for intraoral topical anesthesia

et al. 2021

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To determine whether the permeation capacity and analgesic efficacy of articaine (ATC) could be increased and cytotoxicity decreased by encapsulation in poly(ɛ-caprolactone) nanocapsules (ATCnano), aiming at local or topical anesthesia in dentistry. Cellular viability was evaluated (using the MTT test and fluorescence microscopy) after 1 h and 24 h exposure of HaCaT cells to ATC, ATCnano, ATC with epinephrine (ATCepi), and ATC in nanocapsules with epinephrine (ATCnanoepi). The profiles of permeation of 2% ATC and 2% ATCnano across swine esophageal epithelium were determined using Franz-type vertical diffusion cells. Analgesic efficacy was evaluated with a von Frey anesthesiometer in a postoperative pain model in rats, comparing the 2% ATC, 2% ATCnano, 2% ATCepi, and 2% ATCnanoepi formulations to 4% ATCepi (a commercially available formulation). We show that use of the nanocapsules decreased the toxicity of articaine (P<0.0001) and increased its flux (P = 0.0007). The 2% ATCepi and 4% ATCepi formulations provided higher analgesia success and duration (P<0.05), compared to 2% ATC, 2% ATCnano, and 2% ATCnanoepi. Articaine-loaded poly(ɛ-caprolactone) nanocapsules constitute a promising formulation for intraoral topical anesthesia (prior to local anesthetic injection), although it is not effective when injected in inflamed tissues for pain control, such as irreversible pulpitis.

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“…Inflammatory signals initiate the proliferation and maturation of these two cell types, which is necessary for wound healing 21,22. These two cell lineages have been used in well-defined experimental models in several pharmacology studies, which were designed to investigate intracellular signaling pathways and responses to different types of stimulation 23. The aim of the study was to investigate the influence of 2nd and 3rd generation PAMAM dendrimers on keratinocyte and fibroblast skin cells.…”

Section: Introductionmentioning

confidence: 99%

<p>Effect of 2nd and 3rd generation PAMAM dendrimers on proliferation, differentiation, and pro-inflammatory cytokines in human keratinocytes and fibroblasts</p>

Czarnomysy¹,

Bielawska²,

Bielawski³

2019

IJN

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Background Poly(amidoamine) (PAMAM) dendrimers are of considerable interest when used as a carrier for topical drugs for the skin, although little is known about their possible side effects. Therefore, our study was about the impact of 2nd and 3rd generation PAMAM dendrimers on human keratinocytes and fibroblasts cells. Methods The effect of the tested compounds on collagen biosynthesis was determined using 5[ 3 H]-proline incorporation bioassay. Morphological changes accompanying cell growth inhibition were observed using a confocal microscope. To evaluate the percentage of apoptotic/necrotic cells and the cell growth dynamic of apoptotic features, we performed Annexin V/PI double staining assay, assessed caspase activity, and performed cell cycle analysis by flow cytometry. The flow cytometry method was also used to determine the effect of dendrimers on pro-inflammatory cytokines (IL-6, IL-8 IL-1β). Results The obtained results showed that as the concentration and the generation of dendrimers increased, collagen biosynthesis decreased. We also observed abnormalities in cell differentiation, which may have caused disturbed secretion of pro-inflammatory cytokines. We found that dendrimers cause chronic inflammation which may cause adverse changes in the skin, ultimately– leading to apoptosis in the case of dendrimers in lower concentrations or necrosis at higher concentrations (especially 3rd generation dendrimers). In addition, the inflammatory path induced by the tested compounds was caused by damage in the mitochondria, which we observed as a significant decrease in the mitochondrial membrane potential. Conclusion The results of our study showed that PAMAM dendrimers can cause disorders of cell proliferation and differentiation and may be the cause of cell cycle deregulation and chronic adverse inflammation.

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The effect of two drug delivery systems in ropivacaine cytotoxicity and cytokine release by human keratinocytes and fibroblasts

Abstract: The loss in cell viability was not related to cellular apoptosis. Ropi complexed with HP-β-CD showed a similar cytokine release pattern when compared to the plain formulation. Thus, the HP-β-CD form was a better drug carrier than the MLV form for ropivacaine drug delivery.

Cited by 21 publications

References 55 publications

Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia

Hybrid Hydrogel Composed of Polymeric Nanocapsules Co-Loading Lidocaine and Prilocaine for Topical Intraoral Anesthesia

Promising potential of articaine-loaded poly(epsilon-caprolactone) nanocapules for intraoral topical anesthesia

<p>Effect of 2nd and 3rd generation PAMAM dendrimers on proliferation, differentiation, and pro-inflammatory cytokines in human keratinocytes and fibroblasts</p>

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