Dendrimeric liquid crystals actively modulate cavitation, skin transport pathways, and drug fate during low-frequency sonophoresis

Raquel Petrilli, Patrícia Mazureki Campos, Tais de Cassia Ribeiro, Cristiano Luis Pinto Oliveira, Renata F.V. Lopez

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Abstract

This work presents the first exploration of dendrimeric liquid crystals (DLCs) as dual-function platforms for lowfrequency ultrasound (LFU)–mediated skin delivery. We hypothesized that, beyond acting as drug reservoirs, DLCs could actively modulate cavitation, the formation of localized transport regions (LTRs), and the intradermal microenvironment governing drug partitioning after insonation. Tetrasulfonated zinc phthalocyanine (ZnPcS4), a hydrophilic photosensitizer with poor intrinsic permeability, was selected as a model drug. NMR confirmed the supramolecular association between the PAMAM G2 dendrimer and a fluorinated acid. Polarized light microscopy and SAXS/WAXS demonstrated that when dispersed in a hydroxyethyl cellulose (HEC) hydrogel, DLCs formed stable and highly organized liquid crystalline domains. Drug incorporation and LFU exposure promoted additional rearrangements without disrupting matrix integrity, thereby supporting carrier robustness. Functionally, under LFU, DLC:HEC produced a complete rupture of the aluminum foil, whereas viscosity-matched HEC caused only partial damage, indicating stronger cavitation. This resulted in an approximately threefold expansion of the skin LTR surface coverage (24% vs. 7%). Despite this, DLCs strongly retained ZnPcS4, passively releasing <5% of it; 1 min LFU increased the release by approximately fourfold. In the skin, during direct drug formulation insonation, DLC:HEC enhanced drug deposition in the stratum corneum by nearly one order of magnitude compared to HEC. After LFU pretreatment with drug-free DLC:HEC, DLC-associated domains likely persisted within the LTRs formed in the stratum corneum, establishing a shared microenvironment for subsequently applied formulations. Under these conditions, no statistically significant differences in ZnPcS4 skin distribution or receptor delivery were observed between the HEC and DLC-containing donors, indicating that transport was primarily governed by the preformed LFU-induced pathways and the interaction environment established within the modified stratum corneum. Overall, DLCs actively shape both pathway generation and drug fate in LFU-treated skin, providing a versatile strategy for balancing local retention and transdermal
transport.

Keywords: Dendrimers; Liquid crystals; Ultrasound; Localized transport regions; Transdermal delivery; Zinc phthalocyanine.

Graphical Abstract

Electrospun PVA-PCL/HA nanofiber scaffolds containing mupirocin for surgical wound healing in Sprague Dawley rats

Joyce N. Amajuoyi, Okechukwu C. Ifegwu, Uloma N. Ubani-Ukoma, Bryan C. Okwuba, Chukwuemeka P. Azubuike, Samson O. Adeosun, Renata F.V. Lopez, Bianca Aparecida Martin, Margaret O. Ilomuanya.

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Abstract

Surgical site infections (SSIs) and wound dehiscence are significant postoperative complications that prolong hospital stays and increase treatment costs thus highlighting the need for effective wound dressing options to support healing and minimize scar formation. This study seeks to produce biodegradable electrospun scaffolds for initial burst release and subsequent prolonged release of bioactive substances to enhance wound closure after surgical procedures. Five nanofibrous scaffolds were fabricated using keratin, PCL-PVA blend with CoQ10, mupirocin, and hyaluronic acid at a voltage of 25 – 27 kV, a flow rate of 1 mL/h, at a collection distance of 15 cm. Formulations S1 {PCL, PVA, Keratin}, S2 {PCL, PVA, keratin, Co-enzyme Q10}, S3 {PCL, PVA, keratin, mupirocin}, S4 {PCL, PVA, keratin, CoQ10, mupirocin} SH (PVA, HA) and S5 (bi-layer formulation of SH and S4 with S4 as the bottom layer) were made. Morphological, mechanical, and chemical analyses were conducted on the fabricated nanofibrous scaffolds. Biological characterization, including in vitro cell adhesion, proliferation tests, and drug release, was conducted to assess the scaffolds’ biocompatibility, toxicity, and drug release. The suitability of the scaffolds was tested in surgical wound models in Sprague Dawley rats. Fiber diameters ranged from 1330 nm in S1 to 330 nm in S4, with drug release from S3 and S4 nanofibers sustained for about 36 h. While mupirocin release kinetics were quantified, the inclusion of CoQ10, keratin, and HA was primarily for functional enhancement (antioxidant, hemostatic, ECM-mimetic effects). The incorporation of hyaluronic acid as a second layer in S5 also reduced scar formation. All scaffolds were non-cytotoxic with cell viability above 80%. Scaffold (S5) attained 84.9 ± 3.1% porosity, 310 ± 15% swelling capacity, and a 72° ± 2° contact angle. S5 exhibited 100% wound closure in 9 days and a collagen deposition index of 4.8 ± 0.2. FTIR confirmed additive compatibility, and SEM showed smooth, porous beadless fibers, except in S2 mats. Co-electrospun PVA/PCL- HA fibers offer great potential for controlled delivery of bioactive substances necessary to protect the wound site from infection and minimize scar formation after surgery.

Skin Hydration Potential of a Fluid Gel-Based Formulation of Kappaphycus alvarezii (Rhodophyta, Gigartinales)

Laiara Torres, Bianca Aparecida Martin, Laura de Martin Coletti, Bruna de Souza Altoé Adorno, Juliana da Silva Coppede, Renata Fonseca Vianna Lopez, Suzelei de Castro França, Ana Lucia Fachin and Mozart Marins.

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Abstract

The red alga Kappaphycus alvarezii is a rich source of bioactive compounds with potential applications in the cosmetic industry. This study aimed to characterize a cosmetic serum containing K. alvarezii and evaluate its immediate moisturizing effect on the skin. A randomized, triple-blind, parallel-group clinical trial was conducted with 28 healthy participants, allocated 1:1 to receive either a control formulation with hyaluronic acid or a test formulation with K. alvarezii. The formulations were assessed for stability over 60 days using organoleptic, microbiological, pH, and rheological analyses. Mechanical and bioadhesive properties were assessed using a texture analyzer, while the water content of the stratum corneum on the palms and backs of the hands was measured in vivo using a Corneometer^® CM 825 (Courage & Khazaka Electronic GmbH). Both formulations showed similar stability and rheological behavior. Texture analysis indicated comparable compressibility and elasticity, with a slight reduction in bioadhesive strength for the test formulation. In vivo results demonstrated a moisturizing effect for both formulations, with a significant increase in palmar hydration 60 min after application of the K. alvarezii serum. These findings indicate that the formulation containing K. alvarezii can improve short term skin surface hydration; potential contributions of film formation and barrier modulation remain hypothetical and were not directly assessed in this study.

Sustained insulin-delivery as a growth factor for modulating oral mucosa healing: A case series

Manuela Maria Viana Miguel, Ana Carolina Ferreira Bonafé , Ingrid Fernandes Mathias-Santamaria, Camila Lemos Nunes, Lucas de Paula Ramos, Luciane Dias de Oliveira, Renata Fonseca Vianna Lopez, Renato Corrêa Viana Casarin, Mauro Pedrine Santamaria

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Chlorhexidine antiseptic is a harmful protection due to keratitis and blindness potential

Diego Rocha Gutierrez , Tais de Cassia Ribeiro , Marcelo Caram Ribeiro Fernades, Marianne de Aguiar Vitório Praxedes, Renata Fonseca Vianna Lopez , Fernando Chahud, Eduardo Melani Rocha

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Medical and biological applications of Langevin-type ultrasonic transducers: A narrative review

Gutemberg S. Cardoso, Yugo A. Martins, Renata F.V. Lopez, Antonio A.O. Carneiro, José H. Lopes, Theo Z. Pavan

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Abstract

Power ultrasound is increasingly important in healthcare applications involving non-ionizing radiation. The evolution of piezoelectric-based transducers has enabled the expansion and cost reduction of high-power ultrasonic systems. Among these, Langevin-type transducers are prominent due to their low cost, versatility, and ability to generate high acoustic intensity, which significantly affects the propagation medium. Structurally simple, these devices consist of two metal masses compressing piezoelectric ceramics, secured by a tensioning bolt. For applications demanding high acoustic pressure, mechanical amplifiers can be coupled to intensify ultrasound output. Langevin transducers find extensive use in medical and biological fields. In medicine, they are applied in surgical tools, targeted drug delivery, and cellular stimulation, offering advantages such as cutting precision and tissue selectivity. In biology, they support enzyme activation, microbial control in food, and environmentally friendly biofuel production. Their capacity to enhance biological responses while minimizing invasiveness makes them valuable in both research and clinical contexts. This review explores the main applications of Langevin transducers in biomedical and biotechnological areas. It highlights their functional advantages, operational challenges, and future prospects. By consolidating current knowledge, this paper aims to clarify their role and potential in advancing health-related technologies and sustainable biotechnological solutions.

Keywords: Acoustic cavitation; Langevin transducers; Low-frequency ultrasound; Power ultrasound; Ultrasound in medicine and biology.

Graphical Abstract

Quinazolinones as Bioisosteres of Naphthoquinones: A Path to Potent HsDHODH Inhibitors with Optimized Properties

Bruna F. Godoi, Jéssica D. Bueno, Wemenes J. L. Silva, Aline D. da Purificação, Pedro I. P. Leite, Thiago dos Santos, Murillo Freitas, Daniel G. Silva, Tais C. Silva, Josué de Moraes, Caroline S. Freitas, Mayara Mattos, Thiago M. L. Souza, Bianca A. Martin, Renata F. V. Lopez, M. Cristina Nonato, Carolina H. Andrade, Flavio S. Emery

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Abstract

Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme in pyrimidine biosynthesis and a target for antiviral therapies against RNA viruses like SARS-CoV-2. Building on prior quinone-based inhibitors, we explored quinazolinones as bioisosteric replacements to reduce cytotoxicity and off-target effects. Through structure-based design, we synthesized quinazolinone derivatives aimed at maintaining critical binding interactions. First-generation compounds showed moderate HsDHODH inhibition (up to 60% at 250 μM), with compound 10c having an IC50 of 25 μM. Using computational modeling, we optimized secondgeneration derivatives, with 10e showing the highest potency (IC50 = 0.59 ± 0.03 μM) and significant antiviral activity against SARSCoV-2 (EC50 = 0.15 ± 0.03 μM). These compounds demonstrated improved selectivity compared to naphthoquinone analogs, though challenges with aqueous solubility remain. These results highlight quinazolinones as promising scaffolds for further development of anti-SARS-CoV-2 therapies targeting HsDHODH.

Keywords: human dihydroorotate dehydrogenase, quinazolinones, host-directed therapy, SBDD, SARS-CoV-2

Novel Wide-Spectrum Virucidal Lipid Nanoparticles

Yugo Araújo Martins, Louise Bondeelle, Arnaud Charles-Antoine Zwygart,Thais Melquiades de Lima, Juliano de Paula Souza, Han Kang Tee, Fernando Chahud,Eurico de Arruda Neto, Francesco Stellacci, Renata Fonseca Vianna Lopez, Caroline Tapparel

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Abstract

Viral infections remain a global health challenge, highlighting the urgent need for innovative antiviral strategies. Broad-spectrum antivirals offer a promising solution. Virustatic compounds fail due to their reversible mechanisms, while existing virucidal agents are frequently limited by toxicity. Here, POSTAN, a novel, biocompatible virucidal lipid nanoparticle engineered for direct antiviral activity is presented. Composed of polyoxyethylene sorbitan oleate (PO) and sodium taurodeoxycholate (ST), POSTAN mimics heparan sulfate (HS) proteoglycans and lipid rafts—host cell structures commonly exploited by viruses for attachment. POSTAN demonstrates optimal physicochemical properties for pulmonary delivery, minimal to no toxicity in Vero cells and human airway epithelial (HAE) cultures, and a favorable safety profile in neonatal mice. It exhibits broad-spectrum virucidal activity at micromolar concentrations against herpes simplex virus (HSV), respiratory syncytial virus (RSV), Zika virus, Chikungunya virus (CHIKV), and SARS-CoV-2 by disrupting viral envelopes. In HAE cultures, POSTAN reduced SARS-CoV-2 titers by 5- and 3-log before and after infection. In a neonatal RSV mouse model, intranasal POSTAN led to 6-, 10-, and 19-fold reductions in lung viral titers following prophylactic, therapeutic, or combined prophylactic and therapeutic treatments. It mitigated lung pathology and prevented hemorrhage. These findings support POSTAN as a safe, effective, broad-spectrum antiviral platform for respiratory infections.

Silk-fibroin chitosan film for palatal wounds: Material development, in vitro study, and pilot clinical trial

Ingrid Fernandes Mathias-Santamaria, Manuela Maria Viana Miguel, Ana Carolina Ferreira Bonafé, Camila Nunes Lemos, Lucas de Paula Ramos, Luciane Dias de Oliveira, Renato Correia Vianna Casarin, Renata Fonseca Vianna Lopez, Mauro Pedrine Santamaria

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Abstract

This study aimed to evaluate a novel silk fibroin and chitosan film for treating palatal mucosa wounds. The films were sterilized, tested for physical properties, such as thickness, tensile strength, elongation, water vapor permeability, and swelling, and subjected to scanning electron microscopy. In vitro tests using human oral and skin cells assessed the film’s toxicity. Ten patients undergoing graft-harvesting procedures received the film, and their healing was monitored clinically, immunologically, and histologically. The film demonstrated appropriate physical properties, and laboratory results indicated high cell viability and low toxicity. Clinically, the wounds demonstrated considerable closure by Day 7 and almost full closure by Day 14. Immunological assessments indicated elevation in some healing markers, and histology revealed no residual biomaterial at 12 months post treatment. Complete epithelialization occurred by Day 21, with no tissue thickness loss at 90 days, and patients reported low discomfort and minimal analgesic use. These findings suggest that the silk-fibroin/chitosan film may be beneficial for oral wound healing, warranting further clinical studies to confirm its efficacy.

Keywords: biomaterials, gingival recession, palate, soft tissue therapy, tissue scaffolds, wound healing

Iontophoresis impact on corneal properties using an ex vivo bovine eye model

Gabriela Fávero Galvão, Izabella Cristina Bernardo Maríngolo, Yugo Araújo Martins, Janette Bezebeth Villarruel Muñoz, Marina Zilio Fantucci, Ricardo Roberto da Silva a, Eduardo Melani Rocha, Eloísa Berbel Manaia, Gilles Ponchel, Renata Fonseca Vianna Lopez

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Abstract

This study addresses the challenge of low drug bioavailability in topical ocular administration by developing and validating an ex vivo bovine eye model chamber to evaluate the effects of iontophoresis on drug delivery and corneal properties. Transepithelial electrical resistance (TEER) was assessed as a predictor of corneal epithelial integrity in dissected bovine eyes. TEER measurements were correlated with methylene blue permeation, confirming a threshold of 4.2 kOhm·cm2 as an indicator of epithelial integrity. The model chamber enabled the application of drug solutions around a defined area of the cornea without leakage, facilitating the placement of electrodes and the application of constant electric currents. Applying iontophoresis at 2 mA/cm2 for 6 min significantly increased rhodamine B penetration into the cornea by nearly sixfold compared to passive diffusion (approximately 1.3 µg/cm2 vs. 0.24 µg/cm2), allowing detectable drug levels in the aqueous humor (27.9 ± 0.5 ng/mL). Morphological analyses revealed temporary changes in the cornea, including a 2.3-fold increase in surface roughness (from 44.6 nm to 105.3 nm) and mild collagen disorganization in the stroma, while Bowman’s membrane remained intact. A significant increase in corneal stiffness was noted, with a 200 % rise in the area under the stress–strain curve after iontophoresis. These findings provide insights into iontophoresis-induced changes and highlight the model’s potential for optimizing ocular drug delivery systems. Additionally, the model aligns with the 3Rs principles and could be instrumental in advancing the understanding of anterior segment diseases driven by structural and biomechanical alterations.

Keywords: Ex vivo model; Iontophoresis; Ocular drug delivery systems

Grapphical abstract

Development of a Sensory Neuron-Integrated Skin Spheroid Model for the Evaluation of Neuropeptide-Based Topical Delivery Systems

Bianca Aparecida Martin, Juliana Viegas, Luciana Facco Dalmolin, Emerson de Souza Santos, Izabela Pereira Vatanabe, Sabrina Francesca Lisboa, Renata Fonseca Vianna Lopez, Bruno Sarmento

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Abstract

The skin is a complex organ composed of multiple layers and diverse cell types, including keratinocytes, fibroblasts, adipocytes, and sensory neurons, which maintain its structural and functional integrity together. Conventional in vitro and ex vivo models help investigate drug permeation and selected biological effects. However, they are limited in replicating neural interactions critical for assessing the efficacy of neuropeptide-based therapies. To address this limitation, a sensory neuron-integrated skin spheroid (SS) model was established, incorporating key skin cell types and providing a rapid, adaptable, and physiologically relevant platform for screening the biological activity of topical delivery systems targeting neuronal pathways. The model’s responsiveness was demonstrated using acetyl hexapeptide-3 (HEX-3), a neuropeptide that inhibits acetylcholine release. HEX-3 was internalized by spheroid cells, with preferential accumulation around sensory neurons, confirming targeted cellular uptake. In parallel, ex vivo human skin studies confirmed that HEX-3 can traverse the stratum corneum and accumulate in deeper layers. Treatment with this film enhanced skin hydration, reduced scaling, and improved the structural organization of the stratum corneum after 48 h. Functional assays using the SS model showed that HEX-3 treatment suppressed acetylcholine release, upregulated the antioxidant enzyme SOD2, and stimulated type I collagen synthesis. In aged skin samples, the application of HEX-3 significantly increased collagen levels. This effect was mirrored in the spheroid model, which reached collagen levels comparable to those of aged human skin upon treatment. These findings establish the SS model as a robust platform for evaluating the biological activity of neuropeptide-based topical therapies, offering valuable insights for developing advanced strategies for skin rejuvenation and repair.

Keywords: Aged skin; Acetyl hexapeptide-3; Skin spheroids; Neuronal model; Aging products

Enhancing pulmonary delivery and immunomodulation of respiratory diseases through virus-mimicking nanoparticles

Yugo Araújo Martins, Isabel Cristina Guerra-Gomes, Tamara Silva Rodrigues, Caroline Tapparel, Renata Fonseca Vianna Lopez

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Abstract

This study introduces the nanobromhexine lipid particle (NBL) platform designed for effective pulmonary drug delivery. Inspired by respiratory virus transport mechanisms, NBL address challenges associated with mucus permeation and inflammation in pulmonary diseases. Composed of low molecular weight polyethylene glycol-coated lipid nanoparticles with bromhexine hydrochloride, NBL exhibit a size of 118 ± 24 nm, a neutral zeta potential, osmolarity of 358 ± 28 mOsmol/kg, and a pH of 6.5. Nebulizing without leakage and showing no toxicity to epithelial cells, NBL display mucoadhesive properties with a 60% mucin-binding efficiency. They effectively traverse the dense mucus layer of Calu-3 cultures in an air-liquid interface, as supported by a 55% decrease in MUC5AC density and a 29% increase in nanoparticles internalization compared to non-exposed cells. In assessing immunomodulatory effects, NBL treatment in SARS-CoV-2-infected lung cells leads to a 40-fold increase in anti-inflammatory MUC1 gene expression, a proportional reduction in pro-inflammatory IL-6 expression, and elevated anti-inflammatory IL-10 expression. These findings suggest a potential mechanism to regulate the excessive IL-6 expression triggered by virus infection. Therefore, the NBL platform demonstrates promising potential for efficient pulmonary drug delivery and immunomodulation, offering a novel approach to addressing mucus permeation and inflammation in pulmonary diseases.

Keywords: Lipid nanoparticles; Mucus density reduction; Inflammatory response modulation; Viral respiratory diseases; Coronavirus

Iontophoresis impact on corneal properties using an ex vivo bovine eye model

Gabriela Fávero Galvão, Izabella Cristina Bernardo Maríngolo, Yugo Araújo Martins, Janette Bezebeth Villarruel Muñoz, Marina Zilio Fantucci, Ricardo Roberto da Silva, Eduardo Melani Rocha, Eloísa Berbel Manaia, Gilles Ponchel, Renata Fonseca Vianna Lopez

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Abstract

This study addresses the challenge of low drug bioavailability in topical ocular administration by developing and validating an ex vivo bovine eye model chamber to evaluate the effects of iontophoresis on drug delivery and corneal properties. Transepithelial electrical resistance (TEER) was assessed as a predictor of corneal epithelial integrity in dissected bovine eyes. TEER measurements were correlated with methylene blue permeation, confirming a threshold of 4.2 kOhm·cm2 as an indicator of epithelial integrity. The model chamber enabled the application of drug solutions around a defined area of the cornea without leakage, facilitating the placement of electrodes and the application of constant electric currents. Applying iontophoresis at 2 mA/cm2 for 6 min significantly increased rhodamine B penetration into the cornea by nearly sixfold compared to passive diffusion (approximately 1.3 µg/cm2 vs. 0.24 µg/cm2), allowing detectable drug levels in the aqueous humor (27.9 ± 0.5 ng/mL). Morphological analyses revealed temporary changes in the cornea, including a 2.3-fold increase in surface roughness (from 44.6 nm to 105.3 nm) and mild collagen disorganization in the stroma, while Bowman’s membrane remained intact. A significant increase in corneal stiffness was noted, with a 200 % rise in the area under the stress–strain curve after iontophoresis. These findings provide insights into iontophoresis-induced changes and highlight the model’s potential for optimizing ocular drug delivery systems. Additionally, the model aligns with the 3Rs principles and could be instrumental in advancing the understanding of anterior segment diseases driven by structural and biomechanical alterations.

Keywords: Ex vivo model; Iontophoresis; Ocular drug delivery systems

Iontophoresis-driven alterations in nanoparticle uptake pathway and intracellular trafficking in carcinoma skin cancer cells

Gabriela Fávero Galvão, Raquel Petrilli, Vanessa Cristina Arfelli, Andréia Nogueira Carvalho, Yugo Araújo Martins, Roberta Ribeiro Costa Rosales, Leticia Fröhlich Archangelo, Luis Lamberti Pinto daSilva, Renata Fonseca Vianna Lopez

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Abstract

Effective treatment of squamous cell carcinoma (SCC) poses challenges due to intrinsic drug resistance and limited drug penetration into tumor cells. Nanoparticle-based drug delivery systems have emerged as a promising approach to enhance therapeutic efficacy; however, they often face hurdles such as inadequate cellular uptake and rapid lysosomal degradation. This study explores the potential of iontophoresis to augment the efficacy of liposome and immunoliposome-based drug delivery systems for SCC treatment. The study assessed iontophoresis effects on SCC cell line (A431) viability, nanoparticle uptake dynamics, and intracellular distribution patterns. Specific inhibitors were employed to delineate cellular internalization pathways, while fluorescence microscopy and immunohistochemistry examined changes in EGFR expression and lysosomal activity. Results demonstrated that iontophoresis significantly increased cellular uptake of liposomes and immunoliposomes, achieving approximately 50 % uptake compared to 10 % with passive treatment. This enhancement correlated with modifications in endocytic pathways, favoring macropinocytosis and caveolin-mediated endocytosis for liposomes, and macropinocytosis and clathrin-mediated pathways for immunoliposomes. Moreover, iontophoresis induced alterations in EGFR distribution and triggered syncytium-like cellular clustering. It also attenuated lysosomal activity, thereby reducing nanoparticle degradation and prolonging intracellular retention of therapeutic agents. These findings underscore the role of iontophoresis in modulating nanoparticle internalization pathways, offering insights that could advance targeted drug delivery strategies and mitigate therapeutic resistance in SCC and other malignancies.

Keywords: EGFR; Lysosome degradation; Endocytic routes

Electrostimulable polymeric films with hyaluronic acid and lipid nanoparticles for simultaneous topical delivery of macromolecules and lipophilic drugs

© 2024. Controlled Release Society.

Liquid crystalline nanogel targets skin cancer via low-frequency ultrasound treatment

Tatiana Aparecida Pereira ^a, Danielle Nishida Ramos ^a, Lays Martin Sobral ^a, Yugo Araújo Martins ^a, Raquel Petrilli ^a b, Márcia de Abreu Carvalho Fantini ^c, Andréia Machado Leopoldino ^a, Renata Fonseca Vianna Lopez ^a

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Abstract

The potential of low-frequency ultrasound (LFU) combined with nanotechnology-based formulations in improving skin tumors topical treatment was investigated. The impact of solid lipid nanoparticles (SLN) and hydrophilic nanogels as coupling media on LFU-induced skin localized transport regions (LTR) and the penetration of doxorubicin (DOX) in LFU-pretreated skin was evaluated. SLN were prepared by the microemulsion technique and liquid crystalline nanogels using Poloxamer. In vitro, the skin was pretreated with LFU until skin resistivity of ∼1 KΩ.cm2 using the various coupling media followed by evaluation of DOX penetration from DOX-nanogel and SLN-DOX in skin layers. Squamous cell carcinoma (SCC) induced in mice was LFU-treated using the nanogel with the LFU tip placed 5 mm or 10 mm from the tumor surface, followed by DOX-nanogel application. LFU with nanogel coupling achieved larger LTR areas than LFU with SLN coupling. In LFU-pretreated skin, DOX-nanogel significantly improved drug penetration to the viable epidermis, while SLN-DOX hindered drug transport through LTR. In vivo, LFU-nanogel pretreatment with the 10 mm tip distance induced significant tumor inhibition and reduced tumor cell numbers and necrosis. These findings suggest the importance of optimizing nanoparticle-based formulations and LFU parameters for the clinical application of LFU technology in skin tumor treatment.

Graphical abstract

Keywords: Low frequency ultrasound Doxorubicin Skin cancer therapy Sonophoresis Topical treatment.

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Investigation of the antimicrobial effect of anodic iontophoresis on Gram-positive and Gram-negative bacteria for skin infections treatment

Sofia Gerotto Viola, Luciana Facco Dalmolin, Janette Betzabeth Villarruel Muñoz, Yugo Araújo Martins, Ana Carolina dos Santos Ré, Carolina Patrícia Aires, Renata Fonseca Vianna Lopez

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Highlights

• E. coli is more susceptible to iontophoretic parameter changes than S. epidermidis
• Iontophoresis altered bacteria morphology and induced high rates of E. coli death.
• Anodic iontophoresis can control Gram-negative bacterial proliferation in wounds.

Abstract

Iontophoresis, a non-invasive application of a constant low-intensity electric current, is a promising strategy to accelerate wound healing. Although its mechanisms are not yet fully elucidated, part of its action seems related to inhibiting bacteria growth. This work aimed to investigate the antimicrobial effect of iontophoresis using Staphylococcus epidermidis and Escherichia coli strains, Gram-positive and Gram-negative bacteria, respectively. Anodic iontophoresis was applied to each bacterial suspension using Ag/AgCl electrodes, and bacteria viability was evaluated after 24 h incubation by counting colony-forming units. A Quality-by-Design approach was performed to assess the influence of the iontophoresis’ intensity and application time on bacterial viability. Cell morphology was evaluated by scanning electron microscopy. Iontophoresis showed antimicrobial effects on the Gram-positive bacteria only at 5 mA and 60 min application. However, a linear relationship was observed between intensity and application time for the Gram-negative one, causing drastic morphological changes and up to 98 % death. The cell wall of Gram-negative bacteria seems more susceptible to disorganization triggered by iontophoresis-induced ion transport than Gram-positive ones. Therefore, anodic iontophoresis can be a powerful ally in controlling Gram-negative bacteria proliferation in wounds.

Graphical abstract