Drug-loaded PCL electrospun nanofibers as anti-pancreatic cancer drug delivery systems

Cancer is one of the main causes of death worldwide, being pancreatic cancer the second deadliest cancer in Western countries. Surgery, chemotherapy and radiotherapy form the basis of pancreatic cancer's current treatment. However, these techniques have several disadvantages, such as surgery complications, chemotherapy systemic side effects and cancer recurrence. Drug delivery systems can reduce side effects, increasing the effectivity of the treatment by a controlled release at the targeted tumor cells. In this context, coaxial electrospun fibers can increase the control on the release profile of the drug. The aim of this study was to encapsulate and release different anticancer drugs (5-Fluorouracil and Methotrexate) from a polymeric fiber mat. Different flows and ratios were used to test their effect on fiber morphology, FTIR spectrum, drug encapsulation and release. Good integration of the anticancer drugs was observed and the use of a desiccator for 24 h showed to be a key step to remove solvent remanence. Moreover, the results of this study demonstrated that the polymeric solution could be used to encapsulate and release different drugs to treat cancers. This makes coaxial electrospinning a promising alternative to deliver complex chemotherapies that involve more than one drug, such as FOLFIRINOX, used in pancreatic cancer treatment

TARTESSUS: A customized electrospun drug delivery system loaded with Irinotecan for Local and sustained chemotherapy release in pancreatic cancer

Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL). The mechanical properties and the release kinetics of the drug were adjusted by the electrospinning parameters and by the polymer ratio between 10 w.t.% and 14 w.t.% of PCL in formic acid:acetic acid:chloroform (47.5:47.5:5). The irinotecan release analysis was performed and three different release periods were obtained, depending on the concentration of the polymer in the dissolution. The TARTESSUS device was tested in 2D and 3D cell cultures and it demonstrated a decrease in cell viability in 2D culture between 72 h and day 7 from the start of treatment. In 3D culture, a decrease in viability was seen between 72 h, day 7 (p < 0.001), day 10 (p < 0.001), 14 (p < 0.001), and day 17 (p = 0.003) as well as a decrease in proliferation between 72 h and day 10 (p = 0.030) and a reduction in spheroid size during days 10 (p = 0.001), 14 (p < 0.001), and 17 (p < 0.001). In conclusion, TARTESSUS showed a successful encapsulation of a chemotherapeutic drug and a sustained and delayed release with an adjustable releasing period to optimize the therapeutic effect in pancreatic cancer treatment

Survival of patients receiving a liver transplant for hepatocellular carcinoma, and risk of tumor recurrence

Objective: the goal of this research has been to evaluate the survival, in long and short term, of the patient receiving liver transplant for hepatocellular carcinoma (HCC), the risk of posttransplant tumor relapse and factors related to this complication. Design: retrospective study of a consecutive series of patients having had liver transplant for HCC. Patients and methodology: transplant patients for HCC from 1989 to November 2003. Patients were selected due to general limitations of nodule size and quantity, which were subsequently published as Milan criteria. Also, criteria agreed in the Conference of Barcelona were followed in the pre-transplant diagnosis. Results: the survival of this 81 patients group was of the 80, 61 and 52% for 1, 5 and 10 years respectively. In the 32% of the cases the HCC was an incidental finding in the explant. In the 12.3%, the tumor relapse was verified. The multivariate research identified the size of the nodule (OR = 1,7944) (IC 95% = 1,1332-2,8413) and the vascular invasion (OR = 6,6346) (IC 95% = 1,4624-30,1003) as risk factors of relapse. Conclusions: the liver transplant in selected patients with HCC has good results in medium and long term. The risk of post-transplant tumor relapse becomes notably reduced and is associated with the size of the nodule and the microscopic vascular invasion

Drug-loaded PCL electrospun nanofibers as anti-pancreatic cancer drug delivery systems

Cancer is one of the main causes of death worldwide, being pancreatic cancer the second deadliest cancer in Western countries. Surgery, chemotherapy and radiotherapy form the basis of pancreatic cancer's current treatment. However, these techniques have several disadvantages, such as surgery complications, chemotherapy systemic side effects and cancer recurrence. Drug delivery systems can reduce side effects, increasing the effectivity of the treatment by a controlled release at the targeted tumor cells. In this context, coaxial electrospun fibers can increase the control on the release profile of the drug. The aim of this study was to encapsulate and release different anticancer drugs (5-Fluorouracil and Methotrexate) from a polymeric fiber mat. Different flows and ratios were used to test their effect on fiber morphology, FTIR spectrum, drug encapsulation and release. Good integration of the anticancer drugs was observed and the use of a desiccator for 24 h showed to be a key step to remove solvent remanence. Moreover, the results of this study demonstrated that the polymeric solution could be used to encapsulate and release different drugs to treat cancers. This makes coaxial electrospinning a promising alternative to deliver complex chemotherapies that involve more than one drug, such as FOLFIRINOX, used in pancreatic cancer treatment

TARTESSUS: A customized electrospun drug delivery system loaded with Irinotecan for Local and sustained chemotherapy release in pancreatic cancer

Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL). The mechanical properties and the release kinetics of the drug were adjusted by the electrospinning parameters and by the polymer ratio between 10 w.t.% and 14 w.t.% of PCL in formic acid:acetic acid:chloroform (47.5:47.5:5). The irinotecan release analysis was performed and three different release periods were obtained, depending on the concentration of the polymer in the dissolution. The TARTESSUS device was tested in 2D and 3D cell cultures and it demonstrated a decrease in cell viability in 2D culture between 72 h and day 7 from the start of treatment. In 3D culture, a decrease in viability was seen between 72 h, day 7 (p < 0.001), day 10 (p < 0.001), 14 (p < 0.001), and day 17 (p = 0.003) as well as a decrease in proliferation between 72 h and day 10 (p = 0.030) and a reduction in spheroid size during days 10 (p = 0.001), 14 (p < 0.001), and 17 (p < 0.001). In conclusion, TARTESSUS showed a successful encapsulation of a chemotherapeutic drug and a sustained and delayed release with an adjustable releasing period to optimize the therapeutic effect in pancreatic cancer treatment

TARTESSUS: A Customized Electrospun Drug Delivery System Loaded with Irinotecan for Local and Sustained Chemotherapy Release in Pancreatic Cancer

Post-surgical chemotherapy in pancreatic cancer has notorious side effects due to the high dose required. Multiple devices have been designed to tackle this aspect and achieve a delayed drug release. This study aimed to explore the controlled and sustained local delivery of a reduced drug dose from an irinotecan-loaded electrospun nanofiber membrane (named TARTESSUS) that can be placed on the patients' tissue after tumor resection surgery. The drug delivery system formulation was made of polycaprolactone (PCL)..