Combined Poly(Lactide-Co-Glycolide) Microspheres Containing Diphtheria Toxoid for a Single-shot Immunization.

To develop a single-shot vaccine containing diphtheria toxoid (DT) with a sufficient immune response, poly(lactide-co-glycolide) (PLGA) microspheres were prepared by water-in-oil-in-water double emulsification and solvent extraction techniques using low or high-molecular-weight PLGA (LMW-MS or HMW-MS). Stearic acid (SA) was introduced to HMW-MS (HMW/SA-MS) as a release modulator. Mean particle sizes (dvs, µm) varied between the prepared microspheres, with LMW-MS, HMW-MS, and HMW/SA-MS having the sizes of 29.83, 110.59, and 69.5 µm, respectively; however, the protein entrapment and loading efficiency did not vary, with values of 15.2-16.8 µg/mg and 61-75%, respectively. LMW-MS showed slower initial release (~ 2 weeks) but faster and higher release of antigen during weeks 3~7 than did HMW-MS. HMW/SA-MS showed rapid initial release followed by a continuous release over an extended period of time (~ 12 weeks). Mixed PLGA microspheres (MIX-MS), a combination of HMW/SA-MS and LMW-MS (1:1), demonstrated a sufficient initial antigen release and a subsequent boost release in a pulsatile manner. Serum antibody levels were measured by ELISA after DT immunization of Balb/c mice, and showed a greater response to MIX-MS than to alum-adsorbed DT (control). A lethal toxin challenge test with MIX-MS (a DT dose of 18 Lf) using Balb/c mice revealed complete protection, indicating a good candidate delivery system for a single-shot immunization.

Impact of Postoperative Naples Prognostic Score to Predict Survival in Patients with Stage II-III Colorectal Cancer.

BACKGROUND: The Naples prognostic score (NPS) is a scoring system that reflects a patient's systemic inflammatory and nutritional status. This study aimed to evaluate whether postoperative NPS is effective in assessing the prognosis of stage II-III colorectal cancer (CRC) patients compared with preoperative NPS. METHODS: Between 2005 and 2012, a total of 164 patients diagnosed with stage II-III CRC, who underwent curative resection followed by adjuvant chemotherapy, were divided into two groups: Group 0-1 (NPS = 0-2) and Group 2 (NPS = 3 or 4). Preoperative NPS was calculated based on the results before surgeries, and postoperative NPS was assessed using the results obtained before adjuvant chemotherapy. RESULTS: The overall survival of Group 0-1 was higher than that of Group 2 in both pre- and postoperative NPS assessments. According to the ROC curve analysis, the Area Under the Curve (AUC) ratio for postoperative NPS was 0.64, compared with 0.57 for preoperative NPS, 0.52 for the preoperative neutrophil-lymphocyte ratio (p = 0.032), and 0.51 for the preoperative platelet-lymphocyte ratio (p = 0.027). CONCLUSIONS: Postoperative NPS is effective in predicting the prognosis of stage II-III CRC patients who underwent curative resection followed by adjuvant chemotherapy. The use of NPS could be beneficial in evaluating the prognosis of CRC patients after surgeries.

Efficacy of a bleomycin microneedle patch for the treatment of warts.

Warts are a common skin disease caused by infection of the human papilloma virus. Most treatments involving physical destruction of the infected cells, such as cryotherapy and electrocautery, are limited by intense pain, failure, or recurrences. Our aim was to compare the therapeutic effects of a newly developed bleomycin microneedle patch with cryotherapy in the treatment of warts. Forty-two patients with more than two wart lesions were included in the study. The two treatment modalities were randomly applied to different warts on each patient. Treatment efficacy was assessed using the Physician's Global Assessment (PGA) and the Patient's Global Assessment (PaGA). Mean PGA and PaGA scores were not significantly different between cryotherapy and bleomycin microneedle patch treatment. It was also determined that the mean size of all the warts treated with either modality shrank about equally at weeks 8 and 16 after initial treatment. Thus, treatment efficacy of the bleomycin microneedle patch was comparable to that of conventional cryotherapy. According to a visual analogue scale of pain, bleomycin microneedle patch treatment was significantly less painful than cryotherapy (p < .0001). In addition, use of the bleomycin microneedle patch was more tolerable for patients who were reluctant to receive the painful treatment. Thus, the bleomycin microneedle patch can be an effective, convenient, and innovative treatment modality for warts.

Formulation of a modified-release pregabalin tablet using hot-melt coating with glyceryl behenate.

A modified-release (MR) tablet of the anti-anxiety drug pregabalin (PRE) was prepared by hot-melt coating PRE with glyceryl behenate (GB) as a release retardant and compressing to form a matrix with microcrystalline cellulose (MCC) as a hydrophilic diluent. GB-coated PRE had a size in the range of 177-290 µm with good to acceptable flowability. Tablet hardness decreased slightly as GB content increased. PRE release from the tablet matrices was successfully modified by altering the ratio of MCC and GB, and it was found that dissolution- or diffusion-controlled release depended on the amount of GB used. Drug release was pH-independent. An accelerated stability test on the most promising MR tablet at 40°C and 75% relative humidity for 6 months showed no significant changes in PRE content, and the occurrence of total impurities--including PRE-lactam--was within acceptable limits. After oral administration of the selected MR tablet or a commercial IR capsule (Lyrica) to healthy human volunteers, pharmacokinetic parameters including Tmax, Cmax, AUC0-24, and T1/2 were compared. The confidence interval of AUC0-24 was within the adequate range, but that of Cmax was inadequate. This study demonstrated the potential use of GB for PRE-containing MR formulations.

Enhanced dissolution of celecoxib by supersaturating self-emulsifying drug delivery system (S-SEDDS) formulation.

A supersaturating self-emulsifying drug delivery system (S-SEDDS) was prepared and evaluated for enhanced dissolution of celecoxib (CXB), a poorly water-soluble drug. The selected CXB-dissolved SEDDS formulation consisting 10 % Capryol 90 (oil), 45 % Tween 20 (surfactant), and 45 % Tetraglycol (cosurfactant) had the characteristics of small droplet size and great solubility as 208 nm and 556.7 mg/mL in average, respectively. CXB dissolution from SEDDS in simulated gastric fluid was increased to about 20 % for the initial period of 5 min, but decreased to a half level as time elapsed. Thus, precipitation inhibitors were screened to stabilize the supersaturation. The stabilizing effect of Soluplus, an amphiphilic copolymer, was concentration-dependent, revealing the greatest dissolution of approximately 90 % level with delayed drug crystallization by the addition of the copolymer. CXB dissolution from S-SEDDS was pH-independent. We concluded that S-SEDDS formulation would be very useful in the future for developing oral delivery product of poorly water-soluble drugs.