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Tumor-associated macrophages (TAMs) are an important component of the leukocytic infiltrate of the tumor microenvironment. There is persuasive preclinical and clinical evidence that TAMs induce cancer inanition and malignant progression of primary tumors toward a metastatic state through a highly conserved and fundamental process known as epithelial-mesenchymal transition (EMT). Tumor cells undergoing EMT are distinguished by increased motility and invasiveness, which enable them to spread to distant sites and form metastases. In addition, besides becoming resistant to apoptosis and antitumor drugs, they also contribute to immunosuppression and get a cancer stem-cell like phenotype. Here, we will focus on selected molecular pathways underlying EMT-in particular, the role of TAMs in the induction and maintenance of EMT-and further discuss how the targeting of TAMs through the application of nanotechnology tools allows the development of a whole new range of therapeutics.

Inflammation accounts as one of the major phases in wound healing, while prolonged and chronic inflammation may lead to adverse pathological conditions. Therefore, transdermal delivery of nonsteroidal anti‐inflammatory (NSAIDs) such as encapsulated piroxicam into a nanocarrier seems to be promising. For the first time, a nanoethosomal piroxicam of <200 nm was prepared and combined with iontophoresis. Results showed that there was a critical point at the concentration of 5 mg lecithin with the smallest particle size. Besides, lecithin concentration had direct and inverse linear relationships with turbidity and pH of nanocarriers, respectively. Moreover, as there was no linear relationship between the lecithin concentration and particle size, the effect of lecithin concentration was dominant on turbidity compared with particle size. It seems that a pH higher than 5.5 disturbed the linear relationship of pH and entrapment efficacy percentage (EE%) while at the pH range of 4 to 5.5, the relationship was linear and EE% gradually decreased with increasing pH. These data showed that an optimised nanocarrier with special physicochemical properties is dominant to the just particle size. Besides, ex vivo permeation studies in rat skin showed that there was no significant difference between the permeation of free drug and ethosomal ones. However, iontophoresis significantly enhanced ethosomal piroxicam permeation compared with the free drug. Overall, these data emphasise the superiority of iontophoresis for the transdermal delivery of nanoethosomal medications while nanoethosomal delivery without iontophoresis did not show significant transdermal potential. To sum up, transdermal nanoethosomal piroxicam along with iontophoresis seems to be promising in wound healing.

Prescription of anti‐inflammatory drugs may be considered as a promising strategy in chronic wound healing where the inflammatory disturbance has delayed the healing process. It seems that hydrocortisone 17‐butyrate (HB17) would be promising in the form of a nano‐formulation to enhance drug delivery efficacy. In the present study, transdermal delivery of nano‐HB17 in combination with iontophoresis was investigated ex vivo. Ethosomal‐HB17 was synthesised using lecithin, ethanol and cholesterol with a different ratio by hot method. The negative ethosomal‐HB17 particle size was around 244 ± 4.3 nm with high stability of up to 30 days. Additionally, evaluated entrapment efficiency of HB17 in ethosomes by high performance liquid chromatography was 40.6 ± 2.21%. Moreover, the permeation speed and amount of H17B in complete‐thickness rat skin in the presence and absence of iontophoresis showed that the penetration of free H17B and ethosomal‐H17B formulations were zero and 7.98 μg/cm2 in 120 min, respectively. Whereas in the case of applying iontophoresis, permeation amount obtained was zero and 19.69 μg/cm2 in 30 min in free H17B and ethosomal‐H17B formulations, respectively. It has been concluded that transdermal delivery of ethosomal‐H17B is an effective strategy to enhance drug delivery and it will be improved when it is combined with iontophoresis.