Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB

Neuropathic complications after 157 procedures of continuous popliteal nerve block for hallux valgus surgery. A retrospective study

SummaryBackgroundContinuous peripheral nerve block (CPNB), in particular at the popliteal fossa, is widely used in orthopedic surgery, allowing good postoperative analgesia. Possible neuropathic complications, however, remain poorly known.ObjectiveTo review the characteristics of peripheral neuropathy (PN) after sciatic CPNB at the popliteal fossa, estimating prevalence, severity, evolution and possible risk factors, especially those relating to the procedure.MethodsRetrospective study of PN associated with popliteal fossa CPNB for hallux valgus surgery, between November 1st, 2005 and November 1st, 2009. All procedures were analyzed (type of anesthesia, approach, nerve location technique, number of procedures by operator) with, for each case of PN, analysis of clinical and electromyographic data.ResultsOne hundred and fifty seven sciatic CPNBs were performed (92% women; mean age, 55 years). The approach was lateral (n=62), posterior (n=74) or unknown (n=21). Ultrasound guidance was combined to neurostimulation for 69 patients (44%). Three women (prevalence=1.91%), aged 19, 24 and 65 years respectively, developed associated common superficial peroneal and sural nerve injury (2), axonal on electromyography, with motor (n=1) and/or sensory (n=3) residual dysfunction.DiscussionThe higher prevalence found in the present study than in the literature (0 to 0.5%) raises questions of methodological bias or technical problems. The common peroneal and sural nerves seem to be exposed, unlike the tibial. Several mechanisms can be suggested: anesthetic neurotoxicity, direct mechanical lesion, or tourniquet-related ischemia and conduction block. Further studies are necessary to determine the ideal anesthetic procedure.ConclusionPatients should be informed of the potential risk, however rare, even during mild surgery. The best possible technique should be implemented, with reinforced surveillance.Level of evidenceLevel IV retrospective study