A rapid screening method to select microdialysis carriers for hydrophobic compounds

Abstract

Microdialysis is a minimally invasive sampling technique which is widely applied in many fields including clinical studies. This technique usually has limitation on sampling hydrophobic compounds as aqueous solutions are commonly used as the perfusates. The relative recovery of hydrophobic compounds is often low and irreproducible because of the non-specific binding to microdialysis membranes or catheter tubing. Carriers such as cyclodextrins have been used to improve the recovery and consistency, however the identification of an optimal carrier can only be achieved after time-consuming and costly microdialysis experiments. We therefore developed a rapid, convenient, and low-cost method to identify the optimal carriers for sampling hydrophobic compounds with the use of centrifugal ultrafiltration. Doxorubicin was used as the model compound and its relative recoveries obtained from centrifugal ultrafiltration and from microdialysis were compared. The results show that the relative recoveries are highly correlated (correlation coefficient ≥ 0.9) between centrifugal ultrafiltration and microdialysis when different types or different concentrations of cyclodextrins were used as the carriers. In addition to doxorubicin, this method was further confirmed on three other drugs with different hydrophobicity. This method may facilitate and broaden the use of microdialysis perfusion on sampling or delivering hydrophobic substances in various applications.

Fig 1. Correlation between the RR_U and the RR_M of doxorubicin when using different types of cyclodextrins as carriers.

The cross marks represent the mean values, and the side lengths of the rectangles represent the SD. The Pearson’s correlation analysis shows a correlation coefficient of 0.90 (p = 0.006) which exhibits a high correlation between ultrafiltration and microdialysis.

Fig 2. Correlation between the RR_U and the RR_M of doxorubicin when using different concentrations of γ-CD as carriers.

The cross marks represent the mean values, and the side lengths of the rectangles represent the SD. The Pearson’s correlation analysis shows a correlation coefficient of 0.94 (p = 0.016) which exhibits a high correlation between ultrafiltration and microdialysis.

Fig 3. Carrier screening and method examination on three different drugs.

The RR_U of (A) risperidone, (C) temozolomide, and (E) albumin-bound paclitaxel were tested and screened when different cyclodextrins were used in centrifugal ultrafiltration. Cyclodextrins with high, middle, and low RR_U in (A), (C), and (E) were selected to test their RR_M in (B), (D), and (F) to examine this screening method. The selected groups were respectively filled with dots, slashes, and cross lines. All experimental data are presented in solid circles.