A good drug should cure without harming. A lot depends, however, not so much on the therapeutic substance itself, as on the way it is administered—it should precisely reach the affected area, in a specific amount, for a sufficiently long period of time. This is exactly how mats made of polymer fibers containing the antibacterial metronidazole work.
The mats are produced using an electrospinning method at the Institute of Nuclear Physics of the Polish Academy of Sciences (IFJ PAN) in Cracow, Poland. The study is published in The Journal of Physical Chemistry B.
“Metronidazole is a drug used, among others, for mucous membrane infections of the skin, for example in the treatment of periodontal disease. However, it is known to have some harmful properties, occurring when it unintentionally spreads in the patient’s body,” says Ewa Juszynska-Galazka, professor at the IFJ PAN.
“We set ourselves the task of developing a molecular delivery system for metronidazole which would guarantee its controlled and prolonged release in small amounts exactly where it is needed,” says Prof. Juszynska-Galazka.
She emphasizes that the proposed method, consisting of placing metronidazole in electrospun polymeric fibers, including those with carefully selected coatings, is universal in nature and could potentially be adapted to carry other therapeutic substances.
Electrospinning is a fiber manufacturing technique that has been under development worldwide for a long time. The main role is played by an electrostatic field generated by a high-voltage generator between a needle and a collector plate. When the needle starts to release the spinning solution in a laminar manner, the surface of the expelled liquid starts to stretch and bend.
The identical (positive) electrical charges accumulated on it begin to attract, modifying the shape of the surface. It forms into a cone (called a Taylor cone) with an increasingly narrowing apex, which extends towards the negatively charged collector. The resulting fiber descends in a spiral motion, while undergoing chemical transformations that harden it (depending on the spinning solution, this may be solvent evaporation or polymer deposition).
In order to produce a physically stable multilayer mat, it is necessary to maintain constant environmental conditions (temperature, humidity) as well as system geometry (fixed needle-to-collector distance, type of collector) throughout the process.
In the course of the research at the IFJ PAN, fibers with homogeneous structures and those built from a polymer envelope and a polymer-drug core were produced. In the latter case, a coaxial needle, which can be imagined as a needle within a needle, plays a critical role during electrospinning.
In its outer part, which has a ring cross-section, a solution of the polymer selected for the coating material is introduced, while a mixture of the polymer with the target drug is directed into the central part, responsible for the core of the future fiber.
“In as much as the electrospinning process itself is well understood and in suitable, not particularly complicated, apparatus runs basically spontaneously, matching a polymer or coating to the characteristics of a specific drug is not an easy task.
“The problems that arise here are due to the fact that placing a molecular substance in a nano-restraint usually results in changes in its physical and chemical properties,” explains M. Sc. Olga Adamczyk, who started her research on electrospun fibers containing drugs under the supervision of IFJ PAN professor Małgorzata Jasiurkowska-Delaporte, and intends to continue it as part of her doctoral thesis.
In vitro baseline studies on metronidazole mats, carried out using two types of polymer, established that to provide an adequate surface area for absorption and release of the encapsulated drug, the fiber diameter should be between 0.7 and 1.3 micrometers.
During the storage period, the polymeric fibers with the drug provide an airtight seal to the dressing, while after application they become sufficiently porous in response to the fluids in the environment to start releasing the drug.
Measurements show that the metronidazole contained in the mats is gradually released from them over several hours. However, there is an additional time limitation: the mats can be stored for no more than one month prior to application. Importantly, this limitation is not due to the method of drug delivery, but to the properties of metronidazole itself, which starts to crystallize after this time.
The metronidazole-containing polymer fiber mats produced at IFJ PAN are 2×2 cm in size and in the form of a product potentially ready for therapeutic applications. Their physical and chemical properties are already well understood, so further stages of research will require cooperation with interested scientific and medical institutions.
