Nanodelivery Strategies for Skin Diseases with Barrier Impairment: Focusing on Ceramides and Glucocorticoids

The human epidermis has a characteristic lipidic composition in the stratum corneum, where ceramides play a crucial role in the skin barrier homeostasis and in water-holding capacity. Several skin diseases, such as atopic dermatitis and psoriasis, exhibit a dysfunction in the lipid barrier with altered ceramide levels and increased loss of transepidermal water. Glucocorticoids are normally employed in the therapeutical management of these pathologies. However, they have shown a poor safety profile and reduced treatment efficiency. The main objective of this review is to, within the framework of the limitations of the currently available therapeutical approaches, establish the relevance of nanocarriers as a safe and efficient delivery strategy for glucocorticoids and ceramides in the topical treatment of skin disorders with barrier impairment.

Topical Drug Delivery to the Posterior Segment of the Eye

Topical drug delivery to the posterior segment of the eye is a very complex challenge. However, topical delivery is highly desired, to achieve an easy-to-use treatment option for retinal diseases. In this review, we focus on the drug characteristics that are relevant to succeed in this challenge. An overview on the ocular barriers that need to be overcome and some relevant animal models to study ocular pharmacokinetics are given. Furthermore, a summary of substances that were able to reach the posterior segment after eye drop application is provided, as well as an outline of investigated delivery systems to improve ocular drug delivery. Some promising results of substances delivered to the retina suggest that topical treatment of retinal diseases might be possible in the future, which warrants further research.

Treatment with intralesional methotrexate injection in a patient with nail psoriasis

Psoriasis vulgaris is an inflammatory skin disease involving the skin, nails, and joints. While nail involvement is observed in 70–80% of patients with psoriasis, the rate of patients with isolated nail involvement is 5–10%. Dystrophies arising in the nails in psoriasis affect the patient’s quality of life, and local and systemic therapies may be used as treatment. Intralesional methotrexate or corticosteroid injection might be an option in the treatment of patients with the involvement of one nail or some nails or without the involvement of the skin and joints, due to the side effects of systemic and biological agents. Herein, we report a female patient with nail psoriasis resistant to a previously applied topical treatment, the efficacy of intralesional methotrexate without the use of a systemic antipsoriatic agent, and no progression of side effects.

Enhanced Transdermal Delivery of Pranoprofen Using a Thermo-Reversible Hydrogel Loaded with Lipid Nanocarriers for the Treatment of Local Inflammation

A biocompatible topical thermo-reversible hydrogel containing Pranoprofen (PF)-loaded nanostructured lipid carriers (NLCs) was studied as an innovative strategy for the topical treatment of skin inflammatory diseases. The PF-NLCs-F127 hydrogel was characterized physiochemically and short-time stability tests were carried out over 60 days. In vitro release and ex vivo human skin permeation studies were carried out in Franz diffusion cells. In addition, a cytotoxicity assay was studied using the HaCat cell line and in vivo tolerance study was performed in humans by evaluating the biomechanical properties. The anti-inflammatory effect of the PF-NLCs-F127 was evaluated in adult male Sprague Daw-ley® rats using a model of inflammation induced by the topical application of xylol for 1 h. The developed PF-NLCs-F127 exhibited a heterogeneous structure with spherical PF-NLCs in the hydrogel. Furthermore, a thermo-reversible behaviour was determined with a gelling temperature of 32.5 °C, being close to human cutaneous temperature and thus favouring the retention of PF. Furthermore, in the ex vivo study, the amount of PF retained and detected in human skin was high and no systemic effects were observed. The hydrogel was found to be non-cytotoxic, showing cell viability of around 95%. The PF-NLCs-F127 is shown to be well tolerated and no signs of irritancy or alterations of the skin’s biophysical properties were detected. The topical application of PF-NLCs-F127 hydrogel was shown to be efficient in an inflammatory animal model, preventing the loss of stratum corneum and reducing the presence of leukocyte infiltration. The results from this study confirm that the developed hydrogel is a suitable drug delivery carrier for the transdermal delivery of PF, improving its dermal retention, opening the possibility of using it as a promising candidate and safer alternative to topical treatment for local skin inflammation and indicating that it could be useful in the clinical environment.

Phenytoin: A promising non-antibiotic drug for the topical treatment of digital dermatitis in dairy cows

Background and Aim: Digital dermatitis (DD) is one of the most common causes of lameness in dairy cattle. It is seen in nearly all dairy herds across the world and has substantial welfare and economic implications. In this study, we aimed to investigate the efficacy of phenytoin sodium topical treatment on painful ulcerative stage of bovine digital dermatitis (BDD). Materials and Methods: In total, 45 Holstein-Friesian dairy cows with DD were randomly assigned to one of the three topical treatment trials (15 each): Saline solution (first treatment, negative control), chlortetracycline spray (second treatment, positive control), or phenytoin sodium powder (third treatment, positive control) (third treatment). On day 0 (pre-treatment) and on days 7, 14, 21, and 28 post-treatment, the response of DD-affected cows to the medications used was evaluated by measuring lesion depth and size, as well as the total clinical score (lameness, pain, and discomfort). Results: The cure rate in cows treated with phenytoin (86.66%) on day 28 was significantly improved compared to cows treated with either chlortetracycline (60%) or normal saline (6.66 %). Conclusion: Our findings highlight the superiority of phenytoin over the commonly used antibacterial agent, chlortetracycline, in the topical treatment of BDD, and subsequently suggest that phenytoin should be considered a suitable alternative treatment option for the treatment of BDD.