Non-melanoma skin cancer (NMSC) represents the most common cancer among white skinned people. The term NMSC refers to keratinocyte cancer and essentially to two types of cancer: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC is characterize by local tissue damage and seldom leads to metastatization while SCC can recur and metastasize.
The step that often precedes the onset of this latter tumoral form is called actinic keratosis (AK), that occurs on sun expose skin and may progress to invasive SCC in up to 10% of cases. The treatment of AK and SCC includes invasive approaches (excisional surgery, laser ablation, cryosurgery, curettage and electrodessication), and non-invasive approaches (medical and photodynamic therapy).
Topical pharmaco therapy
Specifically, when surgical treatment is not feasible, topical pharmaco therapy can a viable alternative. Diclofenac, a nonsteroidal anti-inflammatory drug, is the most commonly use topical agent to treat AK, due to its effectiveness, poor side effects, tolerability and low cost. Topical diclofenac, effective use for NMSC, is also report in recent clinical trials. Another therapeutic approach, especially for AK, may derive from the protection of skin keratinocytes from UV induce damages.
In fact, the link between sun exposure and AK skin lesions is well recognize. Excessive exposure to UV radiations may cause mutations in keratinocytes, in particular, UV-A and UV-B radiations induce production of reactive oxygen species (ROS), provoking DNA damage and abnormal cell proliferation. It has been report that the topical use of antioxidants contributes to decreasing the oxidative damage mediate by UV radiation.
In recent years the increasing incidence and morbidity of SCC patients has direct the research towards design of new drug therapies. The multi target approach is consider innovative in drug discovery with encouraging results in various therapeutic fields, especially in the treatment of cancer.
Multi target approach
In conclusion, in the last few years, the multi-target approach seems advantageous for the treatment of complex diseases. For this reason, many hybrids for the treatment of different types of pathologies are propose with encouraging results. However, there are few examples of hybrids use for AK and SCC diseases.
In this work, they synthetize compounds obtaine by combining diclofenac with T and HT; so natural molecules for which antioxidant and anti proliferative activity previously describe; also they evaluate their in vitro activity against AK and SCC models. The hybrid compound 1 has shown a higher antiproliferating activity; hence with respect to native compounds in both AK and SCC models.
Self assembling nanomicelles have been use as carriers for the delivery of the drug; hence to the site of action and in particular the Nano3Hybrid20 result the most effective since; it produce a lower amount of drug permeate through the skin with a consequent reduction of systemic side effects.
Besides, Nano3Hybrid20 formulation improve an adequate drug accumulation; so into the cutaneous layers to provide the same therapeutic activity; so as the commercial reference formulation load with an amount of drug about 5-fold higher. The lower amount of drug coming into contact with the skin contribute; hence to reduce irritative local phenomena, more common for long-term therapy in the precancerous skin lesions.