Formulacija i evaluacija monolitnih matriksnih polimernih filmova za transdermalnu isporuku nitrendipina

The objective of the present work was to develop a suitable transdermal drug delivery system for nitrendipine. Polymeric films of nitrendipine were prepared by the film casting technique (glass ring) on mercury substrate. They were evaluated for physicochemical parameters, in vitro release and ex vivo permeation (heat separated human epidermis). Release of the drug from the films followed anomalous transport (0.5 < n < 1). Polymeric combination containing Eudragit RL 100:PVP K 30 in 4:6 ratio showed the best results. Maximum drug release and skin permeability coefficient in 48 h were 85.8 % and 0.0142 cm h-1, respectively, in formulation C3 (Eudragit RL 100: Plasdone S 630; 4:6) and 88.0 % and 0.0155 cm h-1, respectively, in formulation D3 (Eudragit RL 100: PVP K 30; 4:6). FTIR and TLC studies indicated no drug and polymer interaction.Cilj rada bio je razvoj transdermalnog sustava nitrendipina. Polimerni filmovi nitrendipina pripravljeni su metodom lijevanja (stakleni prsten) na podlozi od žive. Ispitivani su fizičkokemijski parametri, in vitro oslobađanje i ex vivo permeacija (toplinom odvojena humana epiderma). Oslobađanje lijeka iz filmova slijedilo je anomalni transport (0,5 < n < 1). Najbolji rezultati postignuti su kombinacijom polimera Eudragit RL 100 i PVP K 30 u omjeru 4:6. Maksimalno oslobađanje ljekovite tvari i najbolji koeficijent permeacije kroz kožu tijekom 48 h bio je 85,8 %, odnosno 0,0142 cm h1 za formulaciju C3 (Eudragit RL 100 : Plasdone S 630; 4:6) i 88,0 %, odnosno 0,0155 cm h1 za formulaciju D3 (Eudragit RL 100 : PVP K 30; 4:6). FTIR i TLC ukazuju na to da nema interakcije između ljekovite tvari i polimera

Spacecraft Formation Dynamics and Design

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/76961/1/AIAA-13002-440.pd

Dysregulation of PRMT5 in chronic lymphocytic leukemia promotes progression with high risk of Richter's transformation

: Richter's Transformation (RT) is a poorly understood and fatal progression of chronic lymphocytic leukemia (CLL) manifesting histologically as diffuse large B-cell lymphoma. Protein arginine methyltransferase 5 (PRMT5) is implicated in lymphomagenesis, but its role in CLL or RT progression is unknown. We demonstrate herein that tumors uniformly overexpress PRMT5 in patients with progression to&nbsp;RT. Furthermore, mice with B-specific overexpression of hPRMT5 develop a B-lymphoid expansion with increased risk of death, and Eµ-PRMT5/TCL1 double transgenic mice develop a highly aggressive disease with transformation that histologically resembles RT; where large-scale transcriptional profiling identifies oncogenic pathways mediating PRMT5-driven disease progression. Lastly, we report the development of a SAM-competitive PRMT5 inhibitor, PRT382, with exclusive selectivity and optimal in vitro and in vivo activity compared to available PRMT5 inhibitors. Taken together, the discovery that PRMT5 drives oncogenic pathways promoting RT provides a compelling rationale for clinical investigation of PRMT5 inhibitors such as PRT382 in aggressive CLL/RT cases