By pretreating the skin with silicone oil, a team of researchers led by Dr. Munia Ganguli from the Delhi-based Institute of Genomics and Integrative Biology (CSIR-IGIB) has been successful in delivering plasmid DNA into the skin with greater efficiency and without destroying the integrity of the skin. Unlike other enhancers currently being used, preliminary studies show that silicone oil did not get into the skin nor cause any harm. Enhancing the ability of the plasmid DNA, packaged as a nanometer-sized complex with a peptide, to penetrate the skin will go a long way in efficiently delivering drugs for skin disorders. The results were published in the journal Molecular Therapy.
“Topical application of silicone oil on the skin prior to applying the DNA-peptide (which acts as a carrier of DNA) complex allows the DNA to reach the lower part of the epidermal layer of the skin; a little bit of DNA gets into the dermis as well,” says Dr. Ganguli, the corresponding author of the paper.
The skin with its three layers — stratum corneum (top layer), the epidermis (middle layer) and dermis (inner layer) — acts as a tough barrier for the entry of any foreign substance. Since the top layer of the skin is rich in lipids it becomes particularly difficult for the DNA (which is water-loving or hydrophilic) to penetrate it.
Only 30% of cells have the DNA complex when the skin is not pretreated with silicone oil. It increases to 45% once the skin is pretreated. “Silicone oil forms an occlusive layer which prevents water loss from the skin and keeps it well hydrated. The rise in hydration pressure, in turn, opens up many porous pathways for entry of the DNA complexes into the skin,” says Dr. Manika Vij from CSIR-IGIB and the first author of the paper. Besides increased hydration, there are also minor changes in the lipid and protein organisation in the skin.
The use of another enhancer (sodium laureth sulfate-phenyl piperazine — SLA-PP) in place of silicone oil also improves DNA penetration but it was found to damage the skin and was highly toxic to the skin cells; when applied on cell lines, plenty of cells died after 24 hours.
The researchers used hairless mice (the absence of hair follicles makes the skin more closely comparable to human skin) to test the penetration of DNA into the skin. Since the DNA is labelled with fluorescein, it was possible to measure the amount of nanocomplexes that got into the skin by measuring the fluorescence. Other tests revealed that topical application of silicone oil does not damage the integrity of the skin or damage the tissues.
Other potential applications
Talking about potential use of the DNA nanocomplexes along with silicone oil, Dr. Vij says: “In the DNA we can put any gene that encodes for any specific therapeutic protein. This way we can address several skin diseases.”
The researchers are planning to test the ability of the peptide-DNA complexes to cross the skin and enter the blood. “If it does, then it increases the potential to address diseases of other organs,” Dr. Vij says. “We are yet to carry out studies to see if the DNA gets into the blood circulation or gets locally degraded in the skin cells.”