Improvement of cutaneous delivery of methylene blue by liquid crystals

Garcı́a, Marı́a Teresa; Gonçalves, Thalita Pedralino; Martins, Éricka São Félix; Martins, Tereza Silva; Fantini, M.C.A.; Minarini, Paulo Roberto Regazi; Fernandez, Sandra Costa; Salata, Giovanna Cassone; Lopes, Luciana B.

doi:10.1016/j.ijpharm.2018.07.003

Cited by 27 publications

(7 citation statements)

References 51 publications

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“…Methylene blue is a blue dye that acts as a photosensitizer and has been widely employed in studies of transdermal drug penetration 34‐36 . Its advantages are that the depth of penetration into skin can be readily determined by light microscopy of biopsy samples.…”

Section: Discussionmentioning

confidence: 99%

Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma

Xin

Wen

Hamblin

et al. 2020

J of Cosmetic Dermatology

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Background Topical anesthetics are widely used in dermatology and cosmetology to alleviate the pain from nonsurgical cosmetic procedures, while the transdermal drug delivery is limited by the skin barrier. Cold atmospheric plasma (CAP) is a potential approach used for skin pretreatment to enhance transdermal delivery of topical medications. Aims To assess the efficacy of CAP as a pretreatment to improve the transdermal delivery of topical anesthetic. Methods First, we conducted ex vivo permeation studies on 30 mice with a Franz cell diffusion experiment. CAP irradiations of different intensity and duration were pretreated on the epidermal layer of mice before topical lidocaine applied, with the control group received no pretreatment. The amount of drug penetrated through the skin and drug flux were determined by high‐performance liquid chromatography. Then, we treated 3 living mice with CAP followed by application of methylene blue cream (MB) and used skin biopsies to measure penetration depth by microscope. Last, we measured the transepidermal water loss (TEWL) of mouse skin in vivo before and after CAP treatment to observe its effect on the skin barrier function. Results In the permeation study, the transdermal flux of lidocaine was enhanced to 1.97 times of the control samples by CAP pretreatment. We also observed that the accumulative amount of lidocaine varied with the duration of the CAP treatment in a biphasic manner. In the MB penetration study, significant amount of MB deposition was observed under the epidermis and deeper parts of the skin after CAP pretreatment compared with the control sample. A sharp increase in TEWL value was observed directly after the CAP treatment, but 30 minutes later, it began to decrease and recovered to baseline in the next 3 hours, indicating that the skin barrier property had been changed reversibly. Conclusions Our studies suggested that the transdermal absorption of topical lidocaine can be efficiently and safely enhanced by pretreatment of the skin with CAP. We believe that CAP could be used as an assistance to improve analgesia in dermatology.

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Section: Discussionmentioning

confidence: 99%

Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma

Xin

Wen

Hamblin

et al. 2020

J of Cosmetic Dermatology

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“…While the former causes alterations in the cutaneous structure, NPs, due to their greater surface area, accumulate in cutaneous appendages, such as hair follicles, which can bypass the formidable SC barrier. Currently, MB has obtained better penetration results when associated with nanocarriers, as in the study by Garcia et al, who, when developing liquid crystals and comparing the lamellar and hexagonal crystalline phases, obtained greater cutaneous delivery of MB with the phase lamellar, reaching values from 9.79 ± 1.22 to 15.70 ± 1.54 μg/cm 2 in 6 h. Working with another known photosensitizer, the use of sonophoresis increased dermal penetration of zinc phthalocyanine, resulting in reduced viability of melanoma cells [ 29 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

“…To quantify MB in skin layers, a previously developed method was employed with modifications [ 29 ]. Pieces of porcine ear skin obtained from a local slaughterhouse (Fortaleza, Ceará), with an area of 0.95 cm 2 , were used to develop a calibration matrix-based in triplicate.…”

Section: Methodsmentioning

confidence: 99%

Nanoencapsulation of Methylene-Blue for Enhanced Skin Cancer Cell Phototoxicity and Cutaneous Penetration in Association with Sonophoresis

et al. 2023

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Photodynamic therapy (PDT) using methylene blue (MB) as a photosensitizer has emerged as an alternative treatment for skin cancers, such as squamous cell carcinoma (SCC). To increase the cutaneous penetration of the drug, some strategies are used, such as the association of nanocarriers and physical methods. Thus, herein we address the development of nanoparticles based on poly-Ɛ-caprolactone (PCL), optimized with the Box–Behnken factorial design, for topical application of MB associated with sonophoresis. The MB-nanoparticles were developed using the double emulsification-solvent evaporation technique and the optimized formulation resulted in an average size of 156.93 ± 8.27 nm, a polydispersion index of 0.11 ± 0.05, encapsulation efficiency of 94.22 ± 2.19% and zeta potential of −10.08 mV ± 1.12. Morphological evaluation by scanning electron microscopy showed spherical nanoparticles. In vitro release studies show an initial burst compatible with the first-order mathematical model. The nanoparticle showed satisfactory generation of reactive oxygen species. The MTT assay was used to assess cytotoxicity and IC50; values of 79.84; 40.46; 22.37; 9.90 µM were obtained, respectively, for the MB-solution and the MB-nanoparticle without and with light irradiation after 2 h of incubation. Analysis using confocal microscopy showed high cellular uptake for the MB-nanoparticle. With regard to skin penetration, a higher concentration of MB was observed in the epidermis + dermis, corresponding to 9.81, 5.27 μg/cm2 in passive penetration and 24.31 and 23.81 μg/cm2 after sonophoresis, for solution-MB and nanoparticle-MB, respectively. To the best of our knowledge, this is the first report of MB encapsulation in PCL nanoparticles for application in skin cancer using PDT.

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“…This phenomenon should be explained based on the hydration of the corneocyte proteins when in contact with the liquid crystalline phase that may occur at the hydrophilic parts of the protein. This process determines the increase of the interlamellar volume of the lipid bilayer, leading to a disorganization of the stratum corneum barrier that favors the partitioning of hydrophilic drugs like MB [68].…”

Section: Methylene Blue Uses For In Vitro Studiesmentioning

confidence: 99%

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

et al. 2020

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Methylene blue and proflavine are fluorescent dyes used to stain nucleic acid from the molecular level to the tissue level. Already clinically used for sentinel node mapping, detection of neuroendocrine tumors, methemoglobinemia, septic shock, ifosfamide-induced encephalopathy, and photodynamic inactivation of RNA viruses, the antimicrobial, anti-inflammatory, and antioxidant effect of methylene blue has been demonstrated in different in vitro and in vivo studies. Proflavine was used as a disinfectant and bacteriostatic agent against many gram-positive bacteria, as well as a urinary antiseptic involved in highlighting cell nuclei. At the tissue level, the anti-inflammatory effects of methylene blue protect against pulmonary, renal, cardiac, pancreatic, ischemic-reperfusion lesions, and fevers. First used for their antiseptic and antiviral activity, respectively, methylene blue and proflavine turned out to be excellent dyes for diagnostic and treatment purposes. In vitro and in vivo studies demonstrated that both dyes are efficient as perfusion and tissue tracers and permitted to evaluate the minimal efficient concentration in different species, as well as their pharmacokinetics and toxicity. This review aims to identify the optimal concentrations of methylene blue and proflavine that can be used for in vivo experiments to highlight the vascularization of the skin in the case of a perforasome (both as a tissue tracer and in vascular mapping), as well as their effects on tissues. This review is intended to be a comparative and critical presentation of the possible applications of methylene blue (MB) and proflavine (PRO) in the surgical field, and the relevant biomedical findings from specialized literature to date are discussed as well.

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Improvement of cutaneous delivery of methylene blue by liquid crystals

Cited by 27 publications

References 51 publications

Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma

Transdermal delivery of topical lidocaine in a mouse model is enhanced by treatment with cold atmospheric plasma

Nanoencapsulation of Methylene-Blue for Enhanced Skin Cancer Cell Phototoxicity and Cutaneous Penetration in Association with Sonophoresis

Comparative Study Regarding the Properties of Methylene Blue and Proflavine and Their Optimal Concentrations for In Vitro and In Vivo Applications

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