Controlled Release and Cell Viability of Ketoconazole Incorporated in PEG 4000 Derivatives

Abstract

In recent years, polymeric materials have been gaining prominence in studies of controlled release systems to obtain improvements in drug administration. These systems present several advantages compared with conventional release systems, such as constant maintenance in the blood concentration of a given drug, greater bioavailability, reduction of adverse effects, and fewer dosages required, thus providing a higher patient compliance to treatment. Given the above, the present work aimed to synthesize polymeric matrices derived from polyethylene glycol (PEG) capable of promoting the controlled release of the drug ketoconazole in order to minimize its adverse effects. PEG 4000 is a widely used polymer due to its excellent properties such as hydrophilicity, biocompatibility, and non-toxic effects. In this work, PEG 4000 and derivatives were incorporated with ketoconazole. The morphology of polymeric films was observed by AFM and showed changes on the film organization after drug incorporation. In SEM, it was possible to notice spheres that formed in some incorporated polymers. The zeta potential of PEG 4000 and its derivatives was determined and suggested that the microparticle surfaces showed a low electrostatic charge. Regarding the controlled release, all the incorporated polymers obtained a controlled release profile at pH 7.3. The release kinetics of ketoconazole in the samples of PEG 4000 and its derivatives followed first order for PEG 4000 HYDR INCORP and Higuchi for the other samples. Cytotoxicity was determined and PEG 4000 and its derivatives were not cytotoxic.

Keywords: cell viability; controlled release; ketoconazole; polymers; zeta potential.

Figure 1

Chemical structure of the ketoconazole drug [11].

Figure 2

Atomic force microscopy of polymers. PEG 4000 (a), PEG 4000 ACET (b), PEG 4000 HYDR (c), PEG 4000 ETHY (d), PEG 4000 HAL (e), PEG 4000 INCORP (f), PEG 4000 ACET INCORP (g), PEG 4000 HYDR INCORP (h), PEG 4000 ETHY INCORP (i), PEG 4000 HAL INCORP (j).

Figure 3

Photomicrographs of the polymers. PEG 4000 (a), PEG 4000 ACET (b), PEG 4000 ETHY (c), PEG 4000 HAL (d), PEG 4000 HYDR (e), PEG 4000 INCORP (f), PEG 4000 ACET INCORP (g), PEG 4000 ETHY INCORP (h), PEG 4000 HAL INCORP (i), PEG 4000 HYDR INCORP (j).

Figure 4

UV/VIS spectra of ketoconazole.

Figure 5

Controlled release graph of the incorporated polymers at pH 7.3 [11].

Figure 6

Cell viability of PEG 4000 derivatives.

Figure 7

Cell viability of ketoconazole and ketoconazole incorporated in PEG 4000 derivatives.