Pharmacokinetic/pharmacodynamic analysis of adjuvant pegylated interferon α-2b in patients with resected high-risk melanoma

PurposeHigh-dose pegylated interferon α-2b (peginterferon α-2b) significantly decreased disease recurrence in patients with resected stage III melanoma in a clinical study. We investigated the pharmacokinetics (PK) and safety of high-dose peginterferon α-2b in patients with high-risk melanoma.MethodsFor PK analysis, 32 patients received peginterferon α-2b 6 μg/(kg week) subcutaneously for 8 weeks (induction) then 3 μg/(kg week) for 4 weeks (maintenance). PK profiles were determined at weeks 1, 8, and 12. Exposure-response relationships between peginterferon α-2b and absolute neutrophil count (ANC) and alanine aminotransferase (ALT) level were also studied.ResultsPeginterferon α-2b was well-absorbed following SC administration, with a median T (max) of 24 h. Mean half-life estimates ranged from 43 to 51 h. The accumulation factor was 1.69 after induction therapy. PK parameters showed moderate interpatient variability. PK profiles were described by a one-compartmental model with first-order absorption and first-order elimination. Toxicity was profiled and was acceptable; observed side effects were similar to those previously described. Dose reduction produced proportional decreases in exposure and predictable effects on ANC in an Imax model; however, a PK/pharmacodynamic (PK/PD) relationship between peginterferon α-2b and ALT could not be established with high precision.ConclusionsPeginterferon α-2b was well-absorbed and sustained exposure to peginterferon α-2b was achieved with the doses tested. These data confirm and extend previous PK observations of peginterferon α-2b in melanoma and solid tumors. Our PK/PD model of exposure and ANC effect provides useful information for prediction of peginterferon α-2b-related hematologic toxicity

The Synthesis, Self-Assembly and Self-Organisation of Polysilane Block Copolymers

Block copolymers containing polysilane blocks are unique in that the polysilane components possess electro-active properties and are readily photodegradable. This review will discuss and assess the two major approaches to the synthesis of polysilane block copolymers via pre-formed polymer chain coupling and living polymerisation techniques. The self-organisation of polysilane block copolymers and the morphologies adopted in thin films are reviewed. Amphiphilic polysilane-containing block copolymers self-assemble in solvents selective for one block and a number of examples are highlighted. The versatility of these materials is highlighted by recent significant applications including the preparation of hollow crosslinked micellar aggregates in aqueous solutions and in patterned thin film generation subsequently employed as templates for the growth of cell cultures and CaCO (3.

Triply Periodic Minimal Surfaces (TPMS) for the Generation of Porous Architectures Using Stereolithography

International audienceA new generation of sophisticated tissue engineering scaffolds are developed using the periodicity of trigonometric equations to generate triply periodic minimal surfaces (TPMS). TPMS architectures display minimal surface energy that induce typical pore features and surface curvatures. Here we described a series of TPMS geometries and developed a procedure to build such scaffolds by stereolithography using biocompatible and biodegradable photosensitive resin

Templated synthesis of cubic crystalline single networks having large open-space lattices by polymer cubosomes

The synthesis of biophotonic crystals of insects, cubic crystalline single networks of chitin having large open-space lattices, requires the selective diffusion of monomers into only one of two non-intersecting water-channel networks embedded within the template, ordered smooth endoplasmic reticulum (OSER). Here we show that the topology of the circumferential bilayer of polymer cubosomes (PCs)-polymeric analogues to lipid cubic membranes and complex biological membranes-differentiate between two non-intersecting pore networks embedded in the cubic mesophase by sealing one network at the interface. Consequently, single networks having large lattice parameters (> 240 nm) are synthesized by cross-linking of inorganic precursors within the open network of the PCs. Our results pave the way to create triply periodic structures of open-space lattices as photonic crystals and meta-materials without relying on complex multi-step fabrication. Our results also suggest a possible answer for how biophotonic single cubic networks are created, using OSER as templates