Molecular dynamics and physical stability of amorphous nimesulide drug and its binary drug-polymer systems

yesIn this paper we study the effectiveness of three well known polymers: inulin, Soluplus and PVP in stabilizing amorphous form of nimesulide (NMS) drug. The re-crystallization tendency of pure drug as well as measured drug-polymer systems were examined at isothermal conditions by using broadband dielectric spectroscopy (BDS), and at non-isothermal conditions by differential scanning calorimetry (DSC). Our investigation has shown that the crystallization half-life time of pure NMS at 328 K is equal to 33 minutes. We found that this time can be prolonged to 40 years after adding to NMS 20% of PVP polymer. This polymer proved to be the best NMS’s stabilizer, while the worst stabilization effect was found after adding the inulin to NMS. Additionally, our DSC, BDS and FTIR studies indicate that for suppression of NMS’s re-crystallization in NMS-PVP system, the two mechanisms are responsible: the polymeric steric hindrances as well as the antiplastization effect excerted by the excipient.The authors J.K., Z.W., K.G. and M.P., are grateful for the financial support received within the Project No. 2015/16/W/NZ7/00404 (SYMFONIA 3) from the National Science Centre, Poland. H.M. and L.T. are supported by Science Foundation Ireland under grant No. 12/RC/2275 (Synthesis and Solid State Pharmaceuticals Centre)

Dendritic cell immunotherapy versus bevacizumab plus irinotecan in recurrent malignant glioma patients: a survival gain analysis

Stefan-Alexandru Artene,1 Adina Turcu-Stiolica,2 Richard Hartley,1 Marius Eugen Ciurea,3 Oana Daianu,1 Corina Brindusa,1 Oana Alexandru,4 Ligia Gabriela Tataranu,5 Stefana Oana Purcaru,1 Anica Dricu1 1Unit of Biochemistry, 2Department of Biostatistics, 3Department of Plastic and Reconstructive Surgery, 4Department of Neurology, University of Medicine and Pharmacy of Craiova, Craiova, 5Department of Neurosurgery, “Bagdasar–Arseni” Emergency Hospital, Bucharest, Romania Background: The bevacizumab and irinotecan protocol is considered a standard treatment regimen for recurrent malignant glioma. Recent advances in immunotherapy have hinted that vaccination with dendritic cells could become an alternative salvage therapy for the treatment of recurrent malignant glioma.Methods: A search was performed on PubMed, Cochrane Library, Web of Science, ScienceDirect, and Embase in order to identify studies with patients receiving bevacizumab plus irinotecan or dendritic cell therapy for recurrent malignant gliomas. The data obtained from these studies were used to perform a systematic review and survival gain analysis.Results: Fourteen clinical studies with patients receiving either bevacizumab plus irinotecan or dendritic cell vaccination were identified. Seven studies followed patients that received bevacizumab plus irinotecan (302 patients) and seven studies included patients that received dendritic cell immunotherapy (80 patients). For the patients who received bevacizumab plus irinotecan, the mean reported median overall survival was 7.5 (95% confidence interval [CI] 4.84–10.16) months. For the patients who received dendritic cell immunotherapy, the mean reported median overall survival was 17.9 (95% CI 11.34–24.46) months. For irinotecan + bevacizumab group, the mean survival gain was -0.02±2.00, while that for the dendritic cell immunotherapy group was -0.01±4.54.Conclusion: For patients with recurrent malignant gliomas, dendritic cell immunotherapy treatment does not have a significantly different effect when compared with bevacizumab and irinotecan in terms of survival gain (P=0.535) and does not improve weighted survival gain (P=0.620). Keywords: malignant glioma, irinotecan, bevacizumab, dendritic cell, systematic analysi