Drugs administered by typical routes, oral in particular, often suffer from low absorption, short time of action, low activity and adverse effects. These shortcomings may be overcome or at least minimzed by the application of polymeric delivery systems. Polymers are particularly useful for this purpose since they can be used to manufacture various pharmaceutical forms such gels, tablets, films, and patches. They can be injected as millicylindrical implants, microparticles, and in situ-gelling depots. Finally, they may constitute micro- and nanosized carriers  such as microparticles, nanoparticles, nanofibers, polymer–drug conjugates and complexes, polymeric micelles, nanoliposomes, nanoemulsions, and polymersomes.

Goals of the research

The purpose of the study was to obtain delivery systems based on the cationically modified cyclodextrins, which are cyclic oligosaccharides known for their ability to form inclusion complexes with compounds whose molecules fit into the cavity inside the cyclodextrin ring-shaped molecule. This cyclodextrin property enables solubilization of sparingly-soluble drugs and thus enhances their bioavailability and biological activity. On the other hand, cationic modification changes physicochemical and biological properties of cyclodextrins. We have obtained a series of cationically-modified cyclodextrins and used them to improve the delivery of daidzein, a natural isoflavone present in soy, and berberine, an alkaloid compound extracted from the barberry plant.

Results of the research

Cationic derivatives of γ–cyclodextrin were obtained by the substitution with glycidyltrimethylammonium chloride (GTMAC) and ethylenediamine (EDA). They were used to form inclusion complexes with daidzein (DAI). It was found that the complexes were absorbed by the murine hippocampal neuronal cells and human fibroblasts, in which they decreased the level of cellular glycosaminoglycans (GAGs) indicating their potential application for the control the pathological accumulation of GAGs in lysosomal storage diseases. Daidzein complexed with γ–cyclodextrin substituted with ethylenediamine and administered intraperitoneally in rats was absorbed more quickly and its relative bioavailability was about 21 times greater than that of uncomplexed DAI. Daidzein concentration in brain and lungs was almost 90 and 45 times higher, respectively when administered in complex compared to the suspended daidzein

Cationic derivatives of γ–cyclodextrin obtained by substitution with diamines were also studied as delivery vehicles for berberine. The cationic cyclodextrin was found mucoadhesive and resistant to digestion with amylase suggesting that it may constitute an efficient oral delivery system. Berberine complex penetrated the lipid membranes more efficiently than uncomplexed berberine. Berberine was also more toxic to cancerous cells upon complexation and its cellular distribution was different than that of the noncomplexed one.

Collaboration

Poland

Prof. Małgorzata Kajta, Polish Academy of Sciences, Institute of Pharmacology, Department of Experimental Neuroendocrinology, Kraków

Prof. Maria Walczak, Jagiellonian University, Jagiellonian Centre for Experimental Pharmaceutics, Kraków

Czech Republic

Prof. Jana Rudá, Masaryk University, Faculty of Medicine, Department of Pharmacology, Brno