Oleg Kouzbit, Online News Managing Editor

Researchers from Moscow’s Bioengineering Center are harnessing the nano to ease delivery of medicines to afflicted body tissues. With their nano-particles based on sea-born chitosan the scientists aim to minimize adverse side effects of today’s cancer therapies while aiding a drug in getting to the root of a problem.

In its innovative response to the long-standing challenge of safe and efficient drug delivery to an ailing organ, a research team from Moscow’s Bioengineering Center is using a widely known gift of the sea. What they suggest as a nonstop vehicle to give cancer drugs a ride to a neoplasm is nano-modified chitosan, a linear polysaccharide derived commercially from the chitin-rich shells of crabs, shrimps and some other crustaceans, as well as from cell walls of fungi, and already used in bandages and hemostatic agents due to its ability to rapidly clot blood.

The developers claim that nano-particles of this hyaluronic acid polymer are an answer to what has been a plague for many antibiotic-based cancer therapies—quick degradability and toxicity of drugs used. Working with one of the most ‘wayward’ antibiotics, doxorubicine, the Bioengineering Center team is believed to have ‘taught’ chitosan nano-particles to keep the antibiotic from degrading and adversely affecting the heart and kidneys and take doxorubicine straight to the nucleus of a malignant cell.

The particle-sorbed antibiotic is assumed to retain the tumor-fighting power of the original drug while showing much lower toxicity in the human body. This reportedly results in doxorubicine’s longer circulation in blood, which facilitates its delivery to afflicted cells.

According to the developers, the project has been financed from two government grants allocated through the Russian Fund for Fundamental Research and from a 2009-2013 federal program aimed at supporting innovative science. The research’s total cost has yet to be specified.

The developer

Bioengineering Center is a Moscow-based research arm of the Russian Academy of Sciences. Over the past 21 years it has focused on a wide range of fundamental and applied research in genomics; genetic, cell and protein engineering; nano- and biotechnology; bioinformatics; bioethics.

Most advanced areas of the Center’s work also include heterologous gene expression, genetic engineering for agricultural plants and mammalian cells, bio-security issues, and computer-aided solutions for molecular biology and bioinformatics.

Bioengineering Center has 43 Russian patents, its official website says.

Facing a fine line between help and harm…

Years of clinical practice have revealed that anti-tumor pharma solutions present some difficulties when used directly on a neoplastic tissue. For example, doxorubicine, an antibiotic widely used to kill cancer in chemotherapy, quickly decomposes in bloodstream and often causes renal and cardiotoxicity.

To avoid the debilitating side effects researchers typically offer techniques that bind an ‘unruly’ drug with an inert carrier, biologically affined to the human body and unreactive to its chemical compounds and substances. In the Bioengineering Center project, succinylated chitosan used in its nano-modified form is said to help doxorubicine safely penetrate the organic barriers like cell and nuclear membranes, move unswervingly to cancerous cells, and stay in the body much longer than the antibiotic in its conventional form.

…and how it can be remedied

The research team actually ‘crammed’ chitosan nano-particles with doxorubicine to bind and bring the troublesome antibiotic under control while stabilizing its anti-carcinogenic properties.

It was a three-stage process, the developers say. At inception, succinic acid residues were added to chitosan; the ‘hybrid’ was then used to produce a nano-particle suspension. In phase three, doxorubicine molecules were bedded in the nano-particles.

Upon reaching a neoplasm antibiotic-loaded nano-particles disintegrate inside cancerous cells. To monitor the process the researchers labeled the nano-particles with fluorescein, a special dye.

In the experiments, up to 170 micrograms of doxorubicine were attached to one milligram of nano-particles. Being part of the nano-particles the antibiotic reportedly proved as active as unmodified one dissolved in water; both worked their way into cell nuclei at a comparable speed. There was no functional difference between conventional doxorubicine and antibiotic-loaded nano-particles, either, which shows that encapsulating the drug in particles doesn’t affect its full integrity.

Identical to a pure antibiotic in behavior, the new drug carrier beats it in improved toxicity characteristics and much better therapeutic performance, the Bioengineering Center team claims.