AUTHOR=Lee Yoontaek , Park Sun Mi , Song In Ho , Kim Bom Sahn , Park Hyun Soo , Moon Byung Seok , Kim Hyung-Ho 

TITLE=Pharmacokinetic evaluation of paclitaxel, albumin-binding paclitaxel, and liposomal-encapsulated albumin-binding paclitaxel upon gastric subserosal administration

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1381406

DOI=10.3389/fphar.2024.1381406

ISSN=1663-9812

ABSTRACT=<p><bold>Introduction:</bold> Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology.</p><p><bold>Method:</bold> Nine Sprague Dawley rats were divided into three groups: paclitaxel (<italic>n</italic> = 3), albumin-paclitaxel nano-particles (APNs; <italic>n</italic> = 3), and liposome-encapsulated APNs (<italic>n</italic> = 3). [<sup>123</sup>I]Iodo-paclitaxel ([<sup>123</sup>I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using <italic>tert</italic>-butylstannyl substituted paclitaxel as the precursor. Albumin-[<sup>123</sup>I]iodo-paclitaxel nanoparticles ([<sup>123</sup>I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[<sup>123</sup>I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography.</p><p><bold>Results:</bold> Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively.</p><p><bold>Conclusion:</bold> These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.</p>