The aim of this study was to investigate the effects of various stabilizers on the encapsulation efficiency and release of exenatide-loaded PLGA (poly(lactic-co-glycolic acid)) microspheres prepared by the water-in-oil-in-water (W/O/W) solvent evaporation (SE) method. It was shown that the stabilizers affected exenatide stability in aqueous solutions, at water/dichloromethane interfaces, on PLGA surfaces, or during freeze-thawing and freeze-drying procedures. Sucrose predominantly reduces instability generated during freeze-thawing and freeze-drying. Phenylalanine prevents the destabilization at the water–dichloromethane (DCM) interface through decreased adsorption. Poloxamer 188 enhances stability in aqueous solutions and prevents adsorption to PLGA. Proline and lysine decrease adsorption on PLGA surfaces. Fourier transform infra-red spectroscopy (FT-IR) was used to find the molecular interaction of additives with exenatide or PLGA. Additives used in stability assessments were then added stepwise into the inner or outer water phase of the W/O/W double emulsion, and exenatide-loaded microspheres were prepared using the solvent evaporation method. The effect of each stabilizer on the encapsulation efficiency and release behavior of microspheres correlated well with the stability assessment results, except for the negative effect of poloxamer 188. Particle size analysis using laser diffractometry, scanning electron microscopy (SEM), water vapor sorption analysis, differential scanning calorimetry (DSC), and circular dichroism (CD) spectroscopy were also employed to characterize the prepared exenatide-loaded PLGA microsphere. This study demonstrated that an adequate formulation can be obtained by the study about the effect of stabilizers on peptide stability at the preformulation step. In addition, it can help to overcome various problems that can cause the destabilization of a peptide during the microsphere-manufacturing process and sustained drug release.

The purpose of this study was to develop a resveratrol nanosuspension with enhanced oral bioavailability, based on an understanding of the formulation and process parameters of nanosuspensions and using a quality by design (QbD) approach. Particularly, the antisolvent method, which requires no solvent removal and no heating, is newly applied to prepare resveratrol nanosuspension. To ensure the quality of the resveratrol nanosuspensions, a quality target product profile (QTPP) was defined. The particle size (z-average, d90), zeta potential, and drug content parameters affecting the QTPP were selected as critical quality attributes (CQAs). The optimum composition obtained using a 3-factor, 3-level Box–Behnken design was as follows: polyvinylpyrrolidone vinyl acetate (10 mg/mL), polyvinylpyrrolidone K12 (5 mg/mL), sodium lauryl sulfate (1 mg/mL), and diethylene glycol monoethyl ether (DEGEE, 5% v/v) at a resveratrol concentration of 5 mg/mL. The initial particle size (z-average) was 46.3 nm and the zeta potential was −38.02 mV. The robustness of the antisolvent process using the optimized composition conditions was ensured by a full factorial design. The dissolution rate of the optimized resveratrol nanosuspension was significantly greater than that of the resveratrol raw material. An in vivo pharmacokinetic study in rats showed that the area under the plasma concentration versus time curve (AUC0–12h) and the maximum plasma concentration (Cmax) respectively, than those of the resveratrol raw material. Therefore, the prepara values of the resveratrol nanosuspension were approximately 1.6- and 5.7-fold higher,tion of a resveratrol nanosuspension using the QbD approach may be an effective strategy for the development of a new dosage form of resveratrol, with enhanced oral bioavailability.

In this study, we observed unique clinicopathologic features with a very low LNM rate in EGCLS. We consider ESD a potentially curative treatment strategy for EGCLS despite deep submucosal invasion, especially in patients with poor performance status and significant comorbidities.

In our study, advanced stage, C-reactive protein, and treatment with chemotherapeutic agents were related to the occurrence of VTE in patients with cholangiocarcinoma. VTE was an independent unfavorable prognostic factor for survivors of cholangiocarcinoma.

Background/Aims: Recent studies have reported the potentials of endoscopic papillary large balloon dilatation (EPLBD) with minor endoscopic sphincterotomy (EST) for the complete removal of common bile duct (CBD) stone in the high risk groups. However, there have been no reports about the recurrence of the CBD stone after EPLBD with minor EST. The aim of this study was to evlauate the recurrence of CBD stone after EPLBD with minor EST. Methods: A total of 1,036 patients who underwent endoscopic treatment due to CBD stones at Pusan University Hospital were enrolled. The patients were classified into two groups: those who underwent EPLBD with minor EST (group 1) and those who underwent EST treatment (group 2). We investigated clinical factors and recurrence rate between two groups. Results: The recurrence of CBD stone occurred in total of 74 patients (7%), and the recurrence rates of CBD stone were 21/321 (6.5%) in Group 1 and 53/715 (7.4%) in Group 2. There were no difference in the presence of diverticulum and the number and size of recurrent CBD stone between the two groups. In case of diverticulum existence, recurrence rates were 12/158 (7.6%) in Group 1 and 21/101 (20.8%) in Group 2. When compared to the case of no diverticulum existence (Group 1: 9/163 [5.5%], Group 2: 32/614 [5.2%]), the recurrence rate of CBD stone was significantly lower if treated after EPLBD with minor EST (p＜0.01). Conclusions: CBD stone that recurs after going through EPLBD with minor EST can be successfully removed with an endoscopic treatment. The recurrence of CBD stone was especially lower in cases with periampullary diverticulum and treated with EPLBD with minor EST. Our results will be helpful in endoscopic retreatment and preventing the recurrence of CBD stone. (Korean J Gastroenterol 2011;57:352-357)