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

초록

Introduction: 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.Method: Nine Sprague Dawley rats were divided into three groups: paclitaxel (n = 3), albumin-paclitaxel nano-particles (APNs; n = 3), and liposome-encapsulated APNs (n = 3). [123I]Iodo-paclitaxel ([123I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using tert-butylstannyl substituted paclitaxel as the precursor. Albumin-[123I]iodo-paclitaxel nanoparticles ([123I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[123I]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.Results: 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.Conclusion: 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.

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