Pseudoboehmite as a drug delivery system for acyclovir

Abstract

Herpes simplex virus is among the most prevalent sexually transmitted infections. Acyclovir is a potent, selective inhibitor of herpes viruses and it is indicated for the treatment and management of recurrent cold sores on the lips and face, genital herpes, among other diseases. The problem of the oral bioavailability of acyclovir is limited because of the low permeability across the gastrointestinal membrane. The use of nanoparticles of pseudoboehmite as a drug delivery system in vitro assays is a promising approach to further the permeability of acyclovir release. Here we report the synthesis of high purity pseudoboehmite from aluminium nitrate and ammonium hydroxide containing nanoparticles, using the sol-gel method, as a drug delivery system to improve the systemic bioavailability of acyclovir. The presence of pseudoboehmite nanoparticles were verified by infrared spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. In vivo tests were performed with Wistar rats to compare the release of acyclovir, with and without the addition of pseudoboehmite. The administration of acyclovir with the addition of pseudoboehmite increased the drug content by 4.6 times in the plasma of Wistar rats after 4 h administration. We determined that the toxicity of pseudoboehmite is low up to 10 mg/mL, in gel and the dried pseudoboehmite nanoparticles.

Figure 1

DTA and TG analysis of a pseudoboehmite sample containing acyclovir.

Figure 2

DTA and TG analysis of acyclovir.

Figure 3

SEM image of a pseudoboehmite sample.

Figure 4

X-ray diffraction data of a pseudoboehmite sample.

Figure 5

N₂ adsorption isotherm of pseudoboehmite sample.

Figure 6

FTIR spectrum of a pseudoboehmite/acyclovir sample.

Figure 7

FTIR spectrum of acyclovir sample.

Figure 8

TEM image of an aggregate of pseudoboehmite nanoparticles.

Figure 9

Zeta potential of pseudoboehmite gel.

Figure 10

Results of pseudoboehmite gel toxicity using Caco-2 cell line (ATCC) for the (a) dried sample and the (b) pseudoboehmite gel.

Figure 11

Typical chromatograms of acyclovir in different concentrations (22, 108, 542, 1084 and 1626 µg/L).

Figure 12

Calibration curve of acyclovir.

Figure 13

Chromatograms of serum samples of Wistar rats treated without (blue) and with pseudoboehmite (magenta).

Figure 14

Acyclovir concentration in the blood of Wistar rats. Blue is without pseudoboehmite and orange is with pseudoboehmite.