Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles

Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting

Stereotactic Excision of Additional Lesions Detected with Intraoperative Ultrasound Examination During Radiofrequency Dissecting Sealar (Habib®) Assisted Hepatic Metastasectomy: Report of 4 Cases

Intraoperative ultrasound has been using to achieve a proper resection strategy in patients undergoing a hepatic colorectal metastasectomy. This study aims to describe and reveal the place of stereotactic metastasectomy in nonpalpable colorectal liver metastases (CLM). A chart review was initiated for all patients underwent resection for CLM between 2006 and 2011. The data concerning perioperative data and intraoperative strategy were abstracted. Among the 58 patients, who underwent a resection for CLM, 4 (6.9 %) (all men, median age 65.5, range 49–72, years) necessitated a stereotactic metastasectomy. Preoperative evaluations showed 1 (n = 1), 2 (n = 2), or 3 (n = 1) lesions, and intraoperative ultrasound (IUS) found an additional lesion in a case. Stereotactic marking was performed for nonpalpable lesions located in segments IVA, II, and VI and at the junction of segments V and VI. The margins were negative for all lesions both resected with conventional and stereotactic techniques. The examinations of the stereotactic resection materials revealed metastatic adenocarcinoma (patients n = 2), focal nodular hyperplasia (n = 1), and abnormal benign liver histology probably induced by chemotherapy (n = 1). The median (range) operation and hospitalization periods were 217.5 (150–310) minutes and 5.5 (2–9) days. No complications were observed except biliary fistula in a case, which spontaneously disappeared within 2 weeks. A patient died due to systemic disease including hepatic metastases 33 months after the liver surgery. Stereotactic metastasectomy may be feasible for the removal of nonpalpable CLM. Further evaluations are necessitated to understand the accurate place of this novel technique