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Delivery of medical drugs

Particles deliver water-soluble drugs to the body

IPTNanometric spheres with pharmacological agents inside themIPT

Agência FAPESP – A new generation of nanometric systems that deliver medical drugs to the part of the body, where they have to act, is the result of a joint project by researchers from the School of Philosophy, Sciences and Arts of Ribeirão Preto, of the University of São Paulo (FFCLRP-USP) and from the Institute of Technological Research (IPT). The research project generated the filing of a patent and was presented at the 2nd Conference on Innovation in Drug Delivery, which focused on innovation in the delivery of pharmaceuticals. The event was held in Aix-en-Provence, France, in October. “This is a nanocarrier that can deliver hydrophilic (water-soluble) drugs – a veritable feat”, professor Antonio Cláudio Tedesco, from the Chemistry Department of the FFCLRP-USP, told Agência FAPESP.
“Brazil is doing very well in this field; we have been working with more modern systems that sustain the release of the active principle and increase its efficacy”, Tedesco said after the conference. He added that the existing nanocarriers were only successful when they transported hydrophobic substances, which do not dissolve in water. This factor restricted the field of application.  Tedesco studies the development of pharmacological nanocarriers applied to health problems, such as cancer and degenerative diseases of the central nervous system, among others. The delivery system of medical dugs, created in partnership with IPT, stemmed from the doctoral project of biochemist-pharmacist Natália Neto Pereira Cerize, whose advisor is professor Tedesco. Natália got a grant directly from FAPESP up to 2010, when she passed a test to fill a research position at IPT’s Laboratory of Chemical Processes and Particle Technology (LPP). The research study, which has been conducted since 2008 at USP, in partnership with the institute, was coordinated by researcher Maria Inês Ré with the collaboration of researcher Adriano Marim, both of whom are from LPP.

“We made sure we used biocompatible substances that wouldn’t cause any problems in future applications on humans”, said Natália. She also pointed out that the product is versatile and can be used to encapsulate different active principles. “This is why we filed a patent concerning the nanocarrier’s manufacturing process rather than filing a patent related to a medical drug or a specific application”, she explained. Unlike conventional drugs, administered in higher doses so that some of the dosage reaches the desired place, the nanocarriers can deliver much smaller amounts of the active principle. In addition to saving the amount of medication required, this feature reduces the adverse side effects of drugs, as the nanoparticles are designed to aim at a specific biological target. Another advantage is that the nanometric particles control the release of the drug. This characteristic avoids the dose peaks that occur with conventional drugs. The extended release allows the active principles to remain at constant levels in the body.

Industrial scale
The new nanocarrier will be applied in laboratory tests to treat skin cancer in the so-called photodynamic therapy. In this procedure, a topical solution with a photosensitive pharmacological agent is applied to the skin. The solution targets the cancer cells. The action of the medication is activated through exposure to a source of light, which can be a laser or a LED. Exposure to light for a specific amount of time – depending on the case – allows the substances in the medication to kick off a complex process that results in the release of free radicals, the molecules that trigger the apoptosis (programmed cell death) of the affected cells.

“Cancer cells don’t trigger apoptosis. They act as if they had forgotten to die and thus reproduce indefinitely. When free radicals, induced by the beam of light on the photosensitive pharmacological agent, hit the cell, apoptosis is reactivated”, explained Tedesco. Natália points out that another concern of the team was to produce a nanocarrier that could be manufactured on a large scale, using the current equipment of the pharmaceutical industry. “Many research projects generate efficient products that are commercially unfeasible, because they are incompatible with the current pharmaceutical technology”, she explained.

Although it has enormous potential, the patented technology still has a long way to go before it becomes available in pharmacies, say the researchers. The research team has just begun the lab stage of the trials. The next steps include in vitro tests, in vivo animal tests and, finally, clinical tests, with many active principles of interest. “This is an innovative and promising product, with good application prospects. However, many trials must be conducted before it is ready for marketing”, says Natália.

The project
Study of nanocarrier systems for aminolevulinic acid and by-products in photodynamic therapy (nº 2007/07941-4); Type Direct doctoral grant; Advisor Antonio Cláudio Tedesco – USP; Grant holder Natália Neto Pereira Cerize – IPT; Investment R$28,098.56 (FAPESP)