A novel photodynamic therapy-based drug delivery system layered on a stent for treating cholangiocarcinoma.

This study aimed to investigate the drug delivery efficacy and bio-effectiveness of a novel photodynamic therapy (PDT)-matrix drug delivery system for cholangiocarcinoma (CCA). Metallic stents were coated with polyurethane (PU) as the first layer. A 2-hydroxyethyl methacrylate (2-HEMA)/ethylene glycol dimethacrylate (EGDMA)/benzoyl peroxide (BPO) layer and a poly(ethylene-co-vinyl acetate) (PEVA)/poly(n-butyl methacrylate) (PBMA)/polyvinylpyrrolidone K30 (K30) layer containing various concentrations of Photofrin were then incorporated onto the stent as the second and third layers. After incubating the layered membranes with cultured CCA cell line, the release of Photofrin, cell viability, the intracellular uptake of Photofrin, reactive oxygen species (ROS) generation, and apoptosis were determined. Using a single-layer diffusion model, the maximum release of Photofrin from the 5 to 10% K30 formulas was 80 and 100%, respectively, after 24 h. When using the multiple-layer diffusion model, the released Photofrin showed an initial burst of the loading dose from the PEVA/PBMA/K30 layer. In the immobilized model, less than 5% of the Photofrin from the 2-HEMA/EGDMA/BPO layer was released over the 24-h period. Cell viability decreased linearly with increasing Photofrin concentrations, and ROS generation and apoptosis were shown to increase significantly with increasing Photofrin concentrations, until the concentration of Photofrin reached a saturation point of 1.5 µg/ml. This new, multiple-layered, PDT-based stent with dual-release mechanisms is a promising treatment for CCA and cancer-related ductal stenosis.

Prototype of biliary drug-eluting stent with photodynamic and chemotherapy using electrospinning.

BACKGROUND: The combination of biliary stent with photodynamic and chemotherapy seemed to be a beneficial palliative treatment of unresectable cholangiocarcinoma. However, by intravenous delivery to the target tumor the distribution of the drug had its limitations and caused serious side effect on non-target organs. Therefore, in this study, we are going to develop a localized eluting stent, named PDT-chemo stent, covered with gemcitabine (GEM) and hematoporphyrin (HP). METHODS: The prototype of PDT-chemo stent was made through electrospinning and electrospraying dual-processes with an electrical charge to cover the stent with a drug-storing membrane from polymer liquid. The design of prototype used PU as the material of the backing layer, and PCL/PEG blends in different molar ratio of 9:1 and of 1:4 were used in two drug-storing layers with GEM and HP loaded respectively. RESULTS: The optical microscopy revealed that the backing layer was formed in fine fibers from electrospinning, while drug-storing layers, attributed to the droplets from electrospraying process. The covered membrane, the morphology of which was observed by scanning electron microscopy (SEM), covered the stent surface homogeneously without crack appearances. The GEM had almost 100% of electrosprayed efficiency than 70% HP loaded on the covered membrane due to the different solubility of drug in PEG/PCL blends. Drug release study confirmed the two-phased drug release pattern by regulating in different molar ratio of PEG/PCL blends polymer. CONCLUSIONS: The result proves that the PDT-chemo stent is composed of a first burst-releasing phase from HP and a later slow-releasing phase from GEM eluting. This two-phase of drug eluting stent may provide a new prospect of localized and controlled release treatment for cholangiocarcinoma disease.

Non-invasive monitoring method for lower-leg compartment syndrome using a wireless sensor system and finite element analysis.

In this study, a non-invasive pressure monitoring system that is portable and convenient was designed for detecting compartment syndrome. The system combines a wireless module and smartphone, which aids in the achievement of mHealth objectives, specifically, the continuous monitoring of the compartment pressure in patients. A compartment syndrome detecting method using a wireless sensor system and finite element analysis is developed and verified with an in vitro lower-leg model by rapid prototyping. The sensor system is designed to measure a five point pressure variation from the outside of the lower leg and transmit the data to a smartphone via Bluetooth. The analysis model based on the finite element method is employed to calculate the change of pressure and volume inside the four compartments of the lower leg. The in vitro experimental results show that the non-invasive detecting method can monitor the compartment pressure and provide a warning for the occurrence of compartment syndrome if the compartment pressure is higher than 30 mmHg. Furthermore, the theoretical simulation of the real lower leg shows similar trends to those of the in vitro experiments and can promptly detect the occurrence of compartment syndrome. Measured pressure values exceeding 6.3, 2.7, and 2.8 kPa for the three sensors contacting the outside centers of the superficial posterior, anterior, and lateral compartments, respectively, can indicate that each compartment contains a pressure higher than 30 mmHg. These results can provide a warning for the risk of compartment syndrome of each compartment. In addition, the measured values from the three sensors contacting the superficial posterior compartment at the outside center, close to the tibia, and close to the lateral compartment exceeding 1.8, 0.7, and 0.7 kPa, respectively, can indicate the risk of deep posterior compartment syndrome.

Development and clinical trial of a smartphone-based colorimetric detection system for self-monitoring of blood glucose.

Blood glucose measurements help to guide insulin therapy, thus reducing disease severities, secondary complications, and related mortalities. Efforts are underway to allow diabetes patients to experience a more convenient way to measure blood glucose and consequently increase their adherence to regular self-monitoring of blood glucose (SMBG). This study demonstrated a new SMBG system that integrated all components of a glucometer via a smartphone's optical sensing module to detect the colorimetric blood strip and obtains the blood glucose concentration with calculations performed by an application install in the smartphone. To validate the accuracy and applicability of the new SMBG system regarding the ISO15197:2013 accuracy criteria and patient requirements, a clinical trial and usability survey involving participants from different age groups were conducted in collaboration with the China Medical University, where enrolled 120 diabetic patients were asked to operate the new SMBG system to measure their blood glucose concentration, and feedback was obtained from their user experience. The results showed that three different reagent system lots fulfilled the accuracy requirements with values of 97.4-97.5% , and all of the data were within zones A and B of the consensus error grid, which satisfies the ISO 15197:2013 requirement. The usability survey showed that 97.5% of the participants found the operations convenient, and 100% found the design easy for carrying. This new system could lead to improvements in blood glucose monitoring by people with diabetes, and thus, better management of the disease.

Design, fabrication, and feasibility analysis of a colorimetric detection system with a smartphone for self-monitoring blood glucose.

Maintaining appropriate insulin levels is very important for diabetes patients. Effective monitoring of blood glucose can aid in maintaining the body's insulin level, and thus reduce disease severities, secondary complications, and related mortalities. However, existing blood glucose measurement devices are inconvenient to carry and involve complex procedures, reducing the willingness of diabetes patients to regularly measure blood glucose. We aim to provide a rapid, convenient, and portable meter for diabetes patients. We introduce an integrated blood glucose detection device (IBGDD) that has no electronic component and uses the optical sensing module of a smartphone to inspect colorimetric blood strips. To demonstrate accuracy conformance of the developed device to the ISO 15197:2013 standard for blood glucose measurement, 20 diabetes mellitus patients used the IBGDD with smartphones to measure their blood glucose level. The measurement results revealed an accuracy of 100%, completely satisfying the requirements of the ISO 15197:2013 standard. Overall, our specially designed IBGDD with a smartphone could achieve high accuracy and convenient usage for the measurement of blood glucose concentration. Furthermore, the device is highly portable and simple to operate. This contributes toward achieving self-monitoring of blood glucose by diabetes patients and improved mobile health in the future.