Co-delivery drug systems based on ionic graft polymers carrying pharmaceutical anions with antibacterial activities for combined therapy
The studies performed within the project addresses several important issues, i.e. i) biofunctionalization of polymers by the presence of units of choline derivative, ii) the use of amphiphilic graft polymers as stable drug carriers, iii) generating a therapeutic property through the effective exchange of chloride anions with pharmaceutical anions, iv) designing systems containing one or two types of drugs.
Choline has a salt structure containing the 2-hydroxyethyltrimethylammonium cation, where the most common counterion is the chloride anion. This biologically active compound is necessary for the functioning of the body, because it is part of a phospholipid such as lecithin, it is a precursor of acetylcholine, it belongs to vitamin-like substances. In turn, when the counterion is a salicylate anion, then this compound exhibits anti-inflammatory properties and can be used in the acute treatment of sore throats, it also has an analgesic effect, and most importantly is well tolerated by the body. Chemically, choline salts belong to the ionic liquids exhibiting biocompatibility and antibacterial activity. In addition, choline can be used as a monomer in polymer chemistry, which requires the presence of a polymerizable group. Such a methacrylic derivative of choline, i.e. 2-(trimethylammonium)ethyl methacrylate, is a commercially available product, thanks to which the biofunctionalized polymer carriers were obtained.
The control of properties, including biological/biochemical ones, is possible due to the adjustment of structural parameters, which in comparison to the linear polymers are offered in wider range by the grafted polymers, including the degree of grafting and the length of side chains. In turn, the biocompatibility of polymers opens up the possibility of their use as drug carriers that are conjugated with chemical bonds or encapsulated in a polymer matrix through physical interactions. The presence of a polymeric carrier increases the solubility of the drug, but also extends the time of its transport, which allows the critical concentration of free drug in the body to be not exceeded.
Studies have confirmed that poly(ionic liquid)s have great potential for transport of drug that can be introduced in ionic form by counter-ion exchange in the polymer or in a polymerizable ionic liquid. The synthesized polymers delivered the drugs with antibacterial/anti-tuberculosis activity, but the scope could be extended to pharmaceuticals targeting other therapeutic activities.
Moreover, dual bioactive systems for combination therapy containing two different pharmaceuticals were prepared in order to prevent the common drug resistance effect and increase the effectiveness of the treatment. In the bacterial infections, combining two or more drugs is implemented in special situations when the previously used monotherapy has failed. In the case of the conducted studies, the pharmaceutical anions were combined with the second type of pharmaceutical anion (fusidate anions and cloxacillin anions) or drug encapsulated in a polymer matrix (for example salicylic anions and erythromycin, fusidate anions and rifampicin or clindamycin, piperacillin anions and tazobactam, p-aminosalicylate anions and isoniazid, clavulanate anions anions and amoxicillin), which did not reduce the drug content and the effectiveness of its release compared to single drug systems in the form of a pharmaceutical anion, and gained increased biological activity through a controlled co-release mechanism that facilitated the treatment process.
The research was planned taking into account mainly bacterial diseases, i.e. pneumonia, tuberculosis (caused by Streptococcus pneumoniae and Mycobacterium tuberculosis), which belong to the group of civilization diseases due to the current life style, and their ineffective treatments may lead to chronic states supporting the development of tumors. Such a mechanism shows the importance of scientific research, grounded in chemical sciences, which are designed to improve the conventional drugs by designing and implementing polymer drug delivery systems, including combination drug systems, reducing the number of doses taken and extending their duration and therapy effectiveness.
