RESUMO
Gemcitabine (Gem) is a key drug for pancreatic cancer, yet limited by high systemic toxicity, low bioavailability and poor pharmacokinetic profiles. To overcome these limitations, Gem prodrug amphiphiles were synthesised with oleyl, linoleyl and phytanyl chains. Self-assembly and lyotropic mesophase behaviour of these amphiphiles were examined using polarised optical microscopy and Synchrotron SAXS (SSAXS). Gem-phytanyl was found to form liquid crystalline inverse cubic mesophase. This prodrug was combined with phospholipids and cholesterol to create biomimetic Gem-lipid prodrug nanoparticles (Gem-LPNP), verified by SSAXS and cryo-TEM to form liposomes. In vitro testing of the Gem-LPNP in several pancreatic cancer cell lines showed lower toxicity than Gem. However, in a cell line-derived pancreatic cancer mouse model Gem-LPNP displayed greater tumour growth inhibition than Gem using a fraction (<6 %) of the clinical dose and without any systemic toxicity. The easy production, improved efficacy and low toxicity of Gem-LPNP represents a promising new nanomedicine for pancreatic cancer.
Assuntos
Materiais Biomiméticos/uso terapêutico , Desoxicitidina/análogos & derivados , Nanopartículas/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Animais , Materiais Biomiméticos/química , Carboxilesterase/metabolismo , Linhagem Celular Tumoral , Desoxicitidina/metabolismo , Desoxicitidina/uso terapêutico , Dimiristoilfosfatidilcolina/química , Lipossomos/química , Camundongos Endogâmicos NOD , Camundongos SCID , Nanopartículas/química , Pâncreas/patologia , Neoplasias Pancreáticas/patologia , Pró-Fármacos/química , Pró-Fármacos/metabolismo , Suínos , GencitabinaRESUMO
Incisional hernia is a relatively frequent complication of abdominal surgery. The use of mesh to repair incisional and ventral hernias results in lower recurrence rates compared with primary suture techniques. The laparoscopic approach may be associated with lower postoperative morbidity compared with open procedures. Long-term recurrence rates after laparoscopic ventral and incisional hernias are not well defined. A prospective study of the initial experience of a standardized technique of laparoscopic incisional and ventral hernia repair carried out in a tertiary referral hospital was undertaken between January 2003 and February 2007. Laparoscopic hernia repair was attempted in 71 patients and was successful in 68 (conversion rate 4%). The mean age of the patients identified was 63.1 years (39 men and 31 women). Multiple hernial defects were identified in 38 patients (56%), and the mean overall size of the fascial defects was 166 cm(2). The mean mesh size used was 403 cm(2). The mean operative time was 121 minutes. There were six (9%) major complications in this series, but there were no deaths. Hernia recurrence was noted in four patients (6%) at a mean follow up of 20 months. Our preliminary experience indicates that laparoscopic incisional and ventral hernia repair is technically feasible and has acceptable postoperative morbidity and low early recurrence rates.