Eunhye Lee

In vivo antitumor effects of chitosan-conjugated docetaxel after oral administration

The purpose of this study is to evaluate in vivo antitumor efficacy and subacute toxicity of docetaxel (DTX) prodrug comprising a conjugate between DTX and low molecular weight chitosan (LMWC) after oral administration. DTX was covalently attached to LMWC via a cleavable linker so as to be released from LMWC-DTX conjugate in body. In vitro cytotoxicity of LMWC-DTX conjugate was evaluated by MTT assay against two human cancer cell lines, showing similar IC(50) values to the parent DTX. The pharmacokinetic data of the conjugate after oral administration revealed that half-life in blood circulation was increased by approximately 15-fold and AUC((0-infinity)) was 3.8-6.2 times higher in comparison with the intravenously injected DTX (i.v.). In vivo antitumor efficacy was evaluated in nude mice bearing human non-small cell lung carcinoma (NCI-H358) and glioblastoma (U87MG), respectively. The orally administered LMWC-DTX conjugate (10 mg DTX equivalent/kg) showed comparable antitumor efficacy to the same dose of DTX (i.v.) for both NCI-H358 and U87MG models, but revealed much lower subacute toxicity as seen in body weight loss and hematological toxicity.

Amphiphilic drugs as surfactants to fabricate excipient-free stable nanodispersions of hydrophobic drugs for cancer chemotherapy.

Nanoformulations have been extensively explored to deliver water-insoluble drugs, but they generally use exotic new materials, for instance, amphiphilic block copolymers, which must first go through extensively clinical trials and be approved as drug excipients before any clinical uses. We hypothesize that using clinical amphiphilic drugs as surfactants to self-assemble with and thus solubilize hydrophobic drugs will lead to readily translational nanoformulations as they contain no new excipients. Herein, we show the first example of such excipient-free nanodispersions using an amphiphilic anti-tumor drug, irinotecan hydrochloride (CPT11). CPT11 self-assembles with its insoluble active parent drug, 7-ethyl-10-hydroxy camptothecin (SN38), into stable and water-dispersible nanoparticles, increasing SN38s water solubility by thousands of times up to 25 mg/mL with a loading efficiency close to 100%. The versatility of this approach is also demonstrated by fabricating nanodispersions of CPT11 with other water-insoluble drugs including paclitaxel (PTX) and camptothecin (CPT). These nanodispersions have much increased bioavailability and thereby improved anti-cancer activities. Thus, this strategy, using clinically proven amphiphilic drugs as excipients to fabricate nanodispersions, avoids new materials and makes readily translational nanoformulations of hydrophobic drugs.

Pancreatic cancer therapy using an injectable nanobiohybrid hydrogel

Nanobiohybrid hydrogels, which are composed of inorganic nanoparticles and biodegradable polymeric hydrogels, have received special attention in the field of drug and protein delivery. These systems exploit the unique advantages of each component to improve the efficacy of the therapeutic agents and minimize undesirable side effects. The objective of this study was to develop a gemcitabine-loaded nanobiohybrid hydrogel to overcome the limitations of this anticancer drug, such as the very short half-life of gemcitabine (GEM) in plasma, the systemic toxicity from high-dose therapy, and the need for repeated administration during treatment. The proposed injectable nanobiohybrid hydrogel for controlled release of GEM was prepared through intercalation and adsorption of GEM to interlayer galleries and surfaces of montmorillonite (MMT) nanoparticles (forming MMT–GEM complexes), followed by the dispersion of the MMT–GEM complexes into the injectable, biodegradable, temperature-sensitive poly(e-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(e-caprolactone-co-lactide) hydrogel. The MMT–GEM complex and the nanobiohybrid hydrogel were characterized by X-ray diffraction analysis, particle size and zeta potential measurements, Fourier transform infrared spectroscopy, and scanning electron microscopy. Improvements in the properties of nanobiohybrid hydrogel in comparison with the pristine hydrogel were confirmed through sol–gel phase transition diagram, rheological measurement, and in vivo stability. The non-cytotoxicity of the nanobiohybrid hydrogel was proven by MTT assay using the 293T cell line. Compared with the pristine hydrogel, the in vitro GEM release from the nanobiohybrid hydrogel showed a considerably prolonged GEM release time and a much lower initial burst. The antitumor efficacy studies on pancreatic tumor-bearing mice revealed a significant inhibition of tumor growth. Hence, these findings demonstrate that the nanobiohybrid hydrogel is a desirable carrier for controlled release of GEM in the treatment of pancreatic cancer.

ZnO films using a precursor solution irradiated with an electron beam as the cathode interfacial layer in inverted polymer solar cells

We demonstrate the possibility of irradiating sol–gel ZnO with an electron beam (EB-ZnO) to modify sol–gel ZnO, and EB-ZnO is explored as a cathode interfacial layer for inverted polymer solar cells. We investigate the effect of EB-ZnO on the surface, optical and electric properties of sol–gel ZnO films through morphology, chemical composition, optical band gap shift, various defect excitations (photoluminescence) and work function measurement. Oxygen vacancies and the formation of nitrogen on the surface of EB-ZnO films contribute to the formation of n-type degenerated EB-ZnO films. The electric properties of EB-ZnO strongly depend on the adsorbed dose, and EB-ZnO with a suitable dose of 100 kGy improved the power conversion efficiency of inverted polymer solar cells based on PTB7-Th: PC71BM from 8.05% for non-treated sol–gel ZnO to 9.36% for EB-ZnO with an enhanced fill factor.

Rabbit gastric ulcer models: comparison and evaluation of acetic acid-induced ulcer and mucosectomy-induced ulcer

In this study, we examined rabbit gastric ulcer models that can serve as more clinically relevant models. Two types of ulcer model were studied: acetic acid-induced ulcers (AAU) and mucosal resection-induced ulcers (MRU). For AAU, rabbit gastric mucosa was exposed by median laparotomy and treated with bottled acetic acid. MRU was examined as a model for endoscopic mucosal resection (EMR). Normal saline was injected into the submucosal layer and the swollen mucosa was resected with scissors. Endoscopic mucosal resection (EMR) is frequently performed for treatment of early gastric cancers. This procedure inevitably leads to ulcers and bleeding. Bleeding control is the major concern in endoscopic mucosectomy, and some endoscopic hemostatic agents are currently under clinical and preclinical studies. MRU was developed as a model for these induced ulcers and the evaluation of the healing process. The clinical relevancy of those models was compared with that of rat models. Progressive healing was observed for 7 days based on histology. Rabbit models demonstrate round, deep ulcers with clear margins and well-defined healing stages that were difficult to define in rat models.

Simple Formula to Place Central Venous Catheter Tip at T6 After Surgical Cutdown in Neonates

The objective of this paper was to develop a generally applicable formula to estimate correct catheter length after surgical cutdown in right internal jugular vein (RIJV) in neonates. The carina has been utilized as an anatomic landmark indicating superior vena cava-right atrium junction (SVC-RA) for the optimal placement of the central venous catheter (CVC) tip position. However, this landmark may not be accurate in neonates. Recent researches noted that the sixth vertebral body (T6) could better serve as a new landmark of SVC-RA in neonates and smaller children. We prospectively performed RIJV cutdown. For a controlled and reproducible surgical procedure, the venous entry site was consistently taken as the point where the omohyoid muscle crosses the RIJV. On intraoperative infantogram, the vertical distance between the venous entry site and T6 was measured and the catheter was inserted to this length. A linear regression model was investigated using the following variables to elicit the best prediction ...