Tests with topical treatment strategy for fighting skin cancer yield positive results

October 06, 2017

Researchers at the University of São Paulo (USP), in Brazil, are testing a technique in mice that combines low-intensity electric current with a formulation containing nanoencapsulated chemotherapy to treat skin cancer.

Applying a low-intensity unidirectional current is one of the ways to ensure that chemical substances penetrate the skin, pushed into the bloodstream through the electric field using a technique known as iontophoresis.

According to preliminary results of the study, cancer-induced mice which received the formulation combined with iontophoresis presented a significantly greater reduction in the size of the tumor than those that received it through injection.

"One of the challenges involved in this type of topical treatment is ensuring that the drug penetrates the stratum corneum - the outermost layer of the epidermis, composed mainly of dead cells. It is an important tissue barrier against the entry of microorganisms, but it also makes it more difficult for medicines to penetrate," explained Renata Fonseca Vianna Lopez, who supervises the Thematic Project supported by the São Paulo Research Foundation - FAPESP and is also a at the School of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP).

In the case of skin cancer, however, the intent is not that the drug penetrates the tissue to get into the bloodstream, but rather that it becomes concentrated in the area below the stratum corneum that requires treatment. This is the reason why, in the study led by Lopez, she chose to place the chemotherapeutic agent inside nanoparticles.

In vivo tests

Using mice, the researchers induced the formation of a tumor associated with one of the most common types of skin cancer - squamous cell carcinoma - through a subcutaneous injection of human tumor cells that overexpress the epidermal growth factor receptor (EGFR). Lopez explained that the presence of this protein causes the tumor to become more aggressive.

The treatment was conducted using a formulation containing chemotherapy agent 5-fluorouracil encapsulated in a nanoparticle (liposome) that functions as an anti-EGFR antibody. The malignant cells are able to capture a larger quantity of the drug encapsulated in these liposomes.

One group of rodents received the tumor formulation through subcutaneous injections and another group received it through topical application combined with iontophoresis. Lopez compared both methods and thus assessed:

"In addition to reducing the size of the tumor, the topical treatment left the tumor less aggressive. We believe that this method combined with iontophoresis allows the drug to be dispersed over the entire area of the tumor, whereas the subcutaneous application causes it to be concentrated in a single location," Lopez noted.

Versatile technique

In another study, Lopez' group used a stiffer type of polymeric nanoparticle, one containing the anti-inflammatory dexamethasone associated with iontophoresis for the treatment of uveitis - an inflammation of the eye tissue. The results, published in 2015 in the Journal of Controlled Release, is the outcome of the doctoral thesis of Joel Gonçalves Souza, winner of the 2015 Capes Thesis Award in Pharmacy.

"When we apply the medicine directly to the eye, it is quickly eliminated through the defense mechanisms, such as tears. Increased penetration and better results are obtained by using the application method combined with iontophoresis," Lopez said.

Currently, in dissertation research by Camila Lemos, the group plans to test a method that uses iontophoresis in the treatment of chronic wounds such as those that develop in patients with diabetes.

"In this case, we are not dealing with the stratum corneum barrier. We use iontophoresis to assess its influence on release of the substance of interest in a formulation, and to investigate its effect on the growth of microorganisms," Lopez explained.

The strategy consists of placing a peptide having anti-inflammatory properties on a film made of fibers extracted from the cocoon of a silkworm (fibroin). The film is placed on the wound as a dressing, to which an electric current is then applied.

"When we placed the peptide directly on the wound, it degraded very quickly. When placed on the film, however, release occurs in a slower and more sustained way. Iontophoresis allows a larger amount of the peptide to be released from the film at the start of treatment to accelerate healing," the researcher explained.

Lopez went on to say that preliminary results suggest that iontophoresis also stops the proliferation of some types of microorganisms (particularly gram-positive bacteria) that could aggravate wounds.
-end-
About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. For more information: http://www.fapesp.br/en.

Fundação de Amparo à Pesquisa do Estado de São Paulo

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.