Preparation and characterization of amylose-pyrazinamide inclusion complexes

Abstract

Amylose is a linear polymer composed almost entirely of α-1,4-linked units. This biopolymer tends to form single helical inclusion complexes with suitable agents. The study of these complexes presents a great interest since the guest molecules that have been trapped at some stage can be release later, thus leading to many applications, especially in the pharmaceutical and food industry. Amylose is considered as a promising carrier biomaterial of prodrugs [1]. Pyrazinamide (PZA) has long been recognized as an active drug against Mycobacterium tuberculosis, however the administration of PZA in high dosage can cause bacterial resistance. Therefore there is a need for new methodologies which would reduce the administration time and improve therapeutic effect of PZA [2]. The aim of our study was to characterize the amylose-PZA complex. The inclusion complex was prepared by acidification of an alkali solution. Formation and characterization (particle size) of the inclusion complexes in solution were characterized by dynamic light scattering and UV spectroscopy. As the complexation causes changes in the absorption spectrum of a guest molecule, change in the colour of the solution from yellow to colourless was noticed. Furthermore, differences in intensity of the bands, and a slight shift of the absorption spectrum of inclusion complexes, in comparison with the pure amylose solution were observed. The UV analyses confirmed the formation of the amylose-PZA inclusion complexes. DLS analysis has been made for: complexes with pure amylose (without PZA), with PZA (without amylose) and amylose-PZA complexes. The amylose particle size, without the guest molecule, was (101,16±2,60) nm and its relative average poly dispersity index was 0,41±0,04. For the PZA particle the size was (223,70±13,76) nm and its relative average polydispersity index was 0,27±0,10. On the other hand for the amylose-PZA inclusion complexes the size (81,11±1,43) nm was observed and its relative average polydispersity index was 0,26±0,02. As can be seen the size of the complex is smaller than of the pure amylose or PZA particle in solution. This can be attributed to the presence of PZA that induces hydrophobic interactions resulting in the contraction of the complexes and providing a relatively hydrophilic surface. Furthermore, PDI results also indicated that sizes generated from inclusion complexes have a narrow size distribution. Thus, new analysis tests will be conducted to provide more information about structure and morphology of inclusion complexes.