scholarly journals Transungual Delivery of Ciclopirox Is Increased 3–4-Fold by Mechanical Fenestration of Human Nail Plate in an In Vitro Model

Pharmaceutics ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 29 ◽  
Author(s):  
Damian Cordoba Díaz ◽  
Marta Losa Iglesias ◽  
Ricardo Becerro de Bengoa Vallejo ◽  
Manuel Cordoba Diaz

Onychomycosis is a fungal infection of nails that is widespread and difficult to treat because of the impermeable nature of human nails. Topically applied anti-fungal agents cannot penetrate this structure, and treatment regimens often resort to systemic antifungals with concomitant side effects. One recent clinical study suggested that mechanical fenestration of the nail using an intelligent nail drill might be a possible solution to this problem. In this work, an in vitro model of the transungual delivery of antifungal agents is presented, which utilizes real nail tissue and an inline flow system. This system was deployed to measure transungual delivery of ciclopirox and determined that nail fenestration improved drug delivery by 3–4-fold after 42 days. This study bolsters the argument that nail fenestration should be accepted as a pretreatment for onychomycosis and offers a way of evaluating new drugs or formulations designed to combat this condition.

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1616
Author(s):  
Nicoletta di Leo ◽  
Stefania Moscato ◽  
Marco Borso' ◽  
Simona Sestito ◽  
Beatrice Polini ◽  
...  

Recent reports highlighted the significant neuroprotective effects of thyronamines (TAMs), a class of endogenous thyroid hormone derivatives. In particular, 3-iodothyronamine (T1AM) has been shown to play a pleiotropic role in neurodegeneration by modulating energy metabolism and neurological functions in mice. However, the pharmacological response to T1AM might be influenced by tissue metabolism, which is known to convert T1AM into its catabolite 3-iodothyroacetic acid (TA1). Currently, several research groups are investigating the pharmacological effects of T1AM systemic administration in the search of novel therapeutic approaches for the treatment of interlinked pathologies, such as metabolic and neurodegenerative diseases (NDDs). A critical aspect in the development of new drugs for NDDs is to know their distribution in the brain, which is fundamentally related to their ability to cross the blood–brain barrier (BBB). To this end, in the present study we used the immortalized mouse brain endothelial cell line bEnd.3 to develop an in vitro model of BBB and evaluate T1AM and TA1 permeability. Both drugs, administered at 1 µM dose, were assayed by high-performance liquid chromatography coupled to mass spectrometry. Our results indicate that T1AM is able to efficiently cross the BBB, whereas TA1 is almost completely devoid of this property.


2021 ◽  
Vol 11 (5) ◽  
pp. 1977
Author(s):  
Paola Perugini ◽  
Margherita Bonetti ◽  
Marta Guerini ◽  
Giorgio Musitelli ◽  
Pietro Grisoli

Nail fungal infection is often mistakenly considered a minor issue or a purely esthetic problem that is not worth solving. However, onychomycosis has been demonstrated to have a negative impact on a patient’s social life. Therefore, given the poor efficacy of various therapy types, there is strong interest in exploring new methods for evaluating antifungal treatments. As such, the aim of this work was to develop a new protocol, using bovine hoof membranes as a model of the human nail to evaluate the capability of a product claiming to prevent fungal adhesion, which is the first step of the infection. In this work, two specific and representative fungal strains, Trichophyton rubrum and Candida albicans, were used. In order to evaluate the possible protective activity of a product against fungal contamination of the nail plate, it was first necessary to test the affinity of the hoof membranes to be contaminated by the fungi. Then, a pharmaceutical product and a base coat were tested as a positive and negative control, respectively, by introducing the membranes (anti-fungal, basic or no treatment and single vs. multiple treatments) into the fungal suspensions for three different contact times (15 min, 5 h and 24 h). The results showed that the more significant antiadhesive effect (AE) was obtained against Trichophyton rubrum than against Candida albicans. Furthermore, taking into account the results obtained at all testing times, 5 h appeared to be the best time for testing the antiadhesive activity. The results obtained after three treatments with drugs and on washed membranes, in comparison to one single application of antifungal product (AP), demonstrated clearly that the drug was able to penetrate deeper into the membranes to exert itself, even after washing and also after only 15 min of contact. Thus, hoof membrane has been shown to be a valuable in vitro model for this kind of product assessment.


Author(s):  
Hoda Keshmiri Neghab ◽  
Mohammad Hasan Soheilifar ◽  
Gholamreza Esmaeeli Djavid

Abstract. Wound healing consists of a series of highly orderly overlapping processes characterized by hemostasis, inflammation, proliferation, and remodeling. Prolongation or interruption in each phase can lead to delayed wound healing or a non-healing chronic wound. Vitamin A is a crucial nutrient that is most beneficial for the health of the skin. The present study was undertaken to determine the effect of vitamin A on regeneration, angiogenesis, and inflammation characteristics in an in vitro model system during wound healing. For this purpose, mouse skin normal fibroblast (L929), human umbilical vein endothelial cell (HUVEC), and monocyte/macrophage-like cell line (RAW 264.7) were considered to evaluate proliferation, angiogenesis, and anti-inflammatory responses, respectively. Vitamin A (0.1–5 μM) increased cellular proliferation of L929 and HUVEC (p < 0.05). Similarly, it stimulated angiogenesis by promoting endothelial cell migration up to approximately 4 fold and interestingly tube formation up to 8.5 fold (p < 0.01). Furthermore, vitamin A treatment was shown to decrease the level of nitric oxide production in a dose-dependent effect (p < 0.05), exhibiting the anti-inflammatory property of vitamin A in accelerating wound healing. These results may reveal the therapeutic potential of vitamin A in diabetic wound healing by stimulating regeneration, angiogenesis, and anti-inflammation responses.


2011 ◽  
Vol 71 (05) ◽  
Author(s):  
M Salama ◽  
K Winkler ◽  
KF Murach ◽  
S Hofer ◽  
L Wildt ◽  
...  

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