Pharmaceutical Research

Ekins, Sean; Williams, Antony

doi: 10.1007/s11095-010-0059-0pmid: 20107873

Shah, Vinod; Besancon, Luc; Stolk, Pieter; Tucker, Geoffrey; Crommelin, Daan

doi: 10.1007/s11095-009-0048-3pmid: 20107875

The Board of Pharmaceutical Sciences (BPS) of the International Pharmaceutical Federation (FIP) has developed a view on the future of pharmaceutical sciences in 2020. This followed an international conference with invited participants from various fields (academicians, scientists, regulators, industrialists, venture capitalists) who shared their views on the forces that might determine how the pharmaceutical sciences will look in 2020. The commentary here provides a summary of major research activities that will drive drug discovery and development, enabling technologies for pharmaceutical sciences, paradigm shifts in drug discovery, development and regulations, and changes in education to meet the demands of academia, industry and regulatory institutions for pharmaceutical sciences in 2020.

Lund, Paul E.; Hunt, Ryan C.; Gottesman, Michael M.; Kimchi-Sarfaty, Chava

doi: 10.1007/s11095-009-0012-2pmid: 19998056

Over the last two decades, small interfering RNA (siRNA)-mediated gene silencing has quickly become one of the most powerful techniques used to study gene function in vitro and a promising area for new therapeutics. Delivery remains a significant impediment to realizing the therapeutic potential of siRNA, a problem that is also tied to immunogenicity and toxicity. Numerous delivery vehicles have been developed, including some that can be categorized as pseudovirions: these are vectors that are directly derived from viruses but whose viral coding sequences have been eliminated, preventing their classification as viral vectors. Characteristics of the pseudovirions discussed in this review, namely phagemids, HSV amplicons, SV40 in vitro-packaged vectors, influenza virosomes, and HVJ-Envelope vectors, make them attractive for the delivery of siRNA-based therapeutics. Pseudovirions were shown to deliver siRNA effector molecules and bring about RNA interference (RNAi) in various cell types in vitro, and in vivo using immune-deficient and immune-competent mouse models. Levels of silencing were not always determined directly, but the duration of siRNA-induced knockdown lasted at least 3 days. We present examples of the use of pseudovirions for the delivery of synthetic siRNA as well as the delivery and expression of DNA-directed siRNA.

Hureaux, José; Lagarce, Frédéric; Gagnadoux, Frédéric; Rousselet, Marie-Christine; Moal, Valérie; Urban, Thierry; Benoit, Jean-Pierre

doi: 10.1007/s11095-009-0024-ypmid: 20054705

This study demonstrates that a five-day i.v. injection schedule of paclitaxel-loaded LNC dispersions induces no histological or biochemical abnormalities in mice and improves paclitaxel efficacy and therapeutic index in comparison with Taxol®.

Vélez de Mendizábal, Nieves; Martínez-Forero, Iván; Garrido, María; Bandrés, Eva; García-Foncillas, Jesús; Segura, Cristina; Trocóniz, Iñaki

doi: 10.1007/s11095-009-0025-xpmid: 20101520

The major contribution of the model is its new structure and the dynamical consequences, demonstrating an independent behavior between mature and immature B-cells during recovery. The final model could represent a good basis for the optimization of cytotoxic drugs oriented to attain a maximum antitumor efficacy while minimizing hematological toxicity.

Tachibana, Tatsuhiko; Kitamura, Satoshi; Kato, Motohiro; Mitsui, Tetsuya; Shirasaka, Yoshiyuki; Yamashita, Shinji; Sugiyama, Yuichi

doi: 10.1007/s11095-009-0026-9pmid: 20135207

The established kinetic model was found to be rational based on the results that the Km values of P-gp substrates were about the same for cells expressing various levels of P-gp, while the Vmax values were proportional to the expression levels of P-gp.

Mason, Bruce; McCracken, Melissa; Bures, Edward; Kerwin, Bruce

doi: 10.1007/s11095-009-0032-ypmid: 20127149

The presence of oxidants and trace concentrations of metal ions in high purity L-histidine solutions results in the formation of 4(5)-imidazolecarboxaldehyde which has the potential to covalently modify proteins.

Yu, Jing-yu; Rosania, Gus

doi: 10.1007/s11095-009-0034-9pmid: 20099073

The cell-based mechanistic model developed herein is an important step towards the rational design of local, lung-targeted medications, facilitating the design and interpretation of experiments aimed at optimizing drug transport properties in lung.

Bechet, Denise; Tirand, Loraine; Faivre, Béatrice; Plénat, François; Bonnet, Corinne; Bastogne, Thierry; Frochot, Céline; Guillemin, François; Barberi-Heyob, Muriel

doi: 10.1007/s11095-009-0035-8pmid: 20087632

Avdeef, Alex

doi: 10.1007/s11095-009-0036-7pmid: 20069445

R and ε/δ are negatively correlated to a large extent. P app can be rate-limited by either factor, with a wide range of possible combinations still indicating nearly constant leakiness for a given marker.