Title : Drug delivery to the skin: Nanostructures for the treatment of precancerous actinic keratosis
Actinic keratosis (AK) is a common skin disease characterized by cutaneous lesions in the sun-exposed areas of the skin; it is often asymptomatic, but if left untreated it may be the precursor of squamous cell carcinoma (SCC), a non- melanoma skin cancer. The treatment of early clinical lesions can reduce the potential for malignant trasformation that, although treatable, may potentially lead to metastasis or death.
The treatment of AK and SCC includes invasive approaches (excisional surgery, laser ablation…), and non-invasive approaches (medical and photodynamic therapy). Specifically, in case of presence of multiple lesions, topical pharmacotherapy represents an effective way of eradicating both evident and subclinical lesions. Field therapy alone, or in combination with lesion directed therapy, is able to produce high rates of sustained clearance.
Among the topical agents employed to treat AK, diclofenac, a nonsteroidal anti-inflammatory drug, is the most commonly used, due to its effectiveness, poor side effects, tolerability and low cost; side effects include pruritus, erythema, dry skin and rare photosensitivity reactions. Anyway the treatment duration of 60–90 days with twice daily applications might have an impact on practicability and lead to poor adherence.
Besides, as the link between sun exposure and AK skin lesions is well recognised, further therapeutic approaches may derive from the protection of skin keratinocytes from UV-induced damages. It has been reported that the topical use of antioxidants, that have recently showed antiproliferative activity in different types of cancer, contributes to decreasing the oxidative damage mediated by UV radiation. In this context, researchers have focused on developing new drugs and new combination of molecules, such as diclofenac and phytochemical compounds promising as anti- cancer drugs or as lead compounds in the synthesis of new drugs with suitable physicochemical properties for topical delivery (such as size, log P).
In recent years, nanocarriers have been studied to enhance drug bioavailability and reduce skin irritation by avoiding direct contact of the drug with the skin's surface. Delivery of drugs using nanotechnologies, not only can improve drug stability, but also can help overcome the stratum corneum, main barrier to penetration. Moreover, since the main target of AK treatment is the epidermis, in particular the basal layer and in a major extent the granular and cornified layers, nanotechnology-based delivery systems could be able to improve selective tissue distribution, while minimizing systemic side effects.
The assessment of the drug permeation profile and the amount of penetrated drug into the skin layers can be performed with in vitro studies on porcine ear skin, a widely accepted model for human skin.
Audience take away:
• Design of new therapeutics approaches to deliver drugs into the skin
• Influence of nanotechnologies in overcoming skin barriers
• Techniques to investigate drug distribution into the skin