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. 2017:2017:4875784.
doi: 10.1155/2017/4875784. Epub 2017 Nov 29.

Preparation, Characterization, and In Vivo Pharmacoscintigraphy Evaluation of an Intestinal Release Delivery System of Prussian Blue for Decorporation of Cesium and Thallium

Nidhi Sandal  1 , Gaurav Mittal  1 , Aseem Bhatnagar  1 , Dharam Pal Pathak  2 , Ajay Kumar Singh  1
Affiliations

Preparation, Characterization, and In Vivo Pharmacoscintigraphy Evaluation of an Intestinal Release Delivery System of Prussian Blue for Decorporation of Cesium and Thallium

Nidhi Sandal et al. J Drug Deliv. 2017.

Abstract

Background: Prussian blue (PB, ferric hexacyanoferrate) is approved by US-FDA for internal decorporation of Cesium-137 (137Cs) and Thallium-201 (201Tl).

Aim: Since PB is a costly drug, pH-dependent oral delivery system of PB was developed using calcium alginate matrix system.

Methods: Alginate (Alg) beads containing PB were optimized by gelation of sodium alginate with calcium ions and effect of varying polymer concentration on encapsulation efficiency and release profile was investigated. Scanning electron microscopy (SEM) was carried out to study surface morphology. Adsorption efficacy of Alg-PB beads for 201Tl was evaluated and compared with native PB. In vivo pH-dependent release of the formulation was studied in humans using gamma scintigraphy.

Results: Encapsulation efficiencies of Alg-PB beads with 0.5, 1.0, 1.5, and 2.0% polymer solution were 99.9, 91, 92, and 93%, respectively. SEM and particle size analysis revealed differences between formulations in their appearance and size distribution. No drug release was seen in acidic media (pH of 1-2) while complete release was observed at pH of 6.8. Dissolution data was fitted to various mathematical models and beads were found to follow Hixson-Crowell mechanism of release. The pH-dependent release of beads was confirmed in vivo by pharmacoscintigraphy in humans.

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Figures

Figure 1
Figure 1
SEM micrographs of (a) 0.5%, (b) 1%, (c) 1.5%, and (d) 2% PB-Alg beads and cross-sectional view of (e) 1%, (f) 1.5%, and (g) 2% PB-Alg beads.
Figure 2
Figure 2
Cumulative percent release of PB from Alg-PB beads. Error bars represent standard deviation about the means based on 3 × 6 replicates. The pH of dissolution media is 1-2 till 2 hrs. Thereafter pH of the dissolution media changes to 6.8, wherein PB gets released immediately.
Figure 3
Figure 3
PB release from 1% Alg-PB beads at pH of 3, 4, 5, 6, and 7. Error bars represent standard deviation about the means based on 3 × 6 replicates.
Figure 4
Figure 4
Adsorption efficiency of Alg-PB beads for 201Tl. Error bars represent standard deviation about the means based on three replicates.
Figure 5
Figure 5
Release profile of radioactivity (technetium-99m pertechnetate, 99mTcO4−) from 99mTcO4− loaded Alg-PB beads.
Figure 6
Figure 6
Image showing 32-minute continuous dynamic imaging of subject 1. Gamma camera was focused on lower abdomen and intestines. Each frame lasted for 30 sec and the movements of beads were observed in 38th frame (at 19 min).
Figure 7
Figure 7
Graph showing the blood pool activity as counts per sec as a function of time.
See this image and copyright information in PMC

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