Nanostructured Formulations in Skin Cancer: Challenges and Perspectives

The incidence of skin cancer, the most common malignant disease that mainly affects the Caucasian population, is increasing worldwide. There are three main types of skin cancers: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. The first two are grouped as non-melanoma skin cancers: BCC is characterized by local tissue damage and seldom leads to metastasization while SCC can recur and metastasize. Melanoma is a cancer with dark pigment that develops from the  pigment-containing cells known  as melanocytes.   Surgical  excision  of these malignancies has  been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including comorbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances, e.g. when the patients present with field cancerization or multiple clinical and subclinical lesions over a large anatomical area. Topical treatment potentially allows for higher drug levels  at  the  tumour  site,  and may  result  in  less  overall  toxicity than  systemic  agents.  Despite  the numerous positive  aspects, the topical way is also not without limitations, such as poor bioavailability, undesirable local side effects compromising the therapeutic efficacy (erythema, paresthesia, rash, edema, contact dermatitis). An ideal treatment should be developed taking into account the good patient compliance, a better overall efficiency of the treatment, a toxicity as low as possible, a high ability to  reach  the  target  site  in  an  amount  sufficient  to  give  the  therapeutic  effect.    The  success  of  the  topical  therapy  depends  on  both the pharmacologically active substance and the formulation strategy. Researchers have focused on developing new drugs and new combination of molecules, such as conventional cancer chemotherapeutics and phytochemical compounds promising as anti-cancer drugs or as lead compounds in the synthesis of new drugs. The physicochemical properties of molecules, such as size and Log P, are important issues in selecting a candidate for topical delivery.  Nanotechnology based formulations can help in achieving our goal: enhancement of drug bioavailability and reduction of 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 to overcome the stratum corneum, main barrier to penetration. The assessment of the drug penetration profile into the skin layers can be performed with in vitro penetration studies on porcine ear skin, allowing the determination of the amount of penetrated drug within the stratum corneum, epidermis and dermis and hair follicles and the relative penetration depth. .