Controlled delivery of follicle-stimulating hormone in cattle.

Embryo transfer in cattle is a key issue requiring in vivo production of several mature follicles as opposed to the normal production of only one. In vivo produced embryos can then be transferred to recipient cows for gestation to occur. To obtain a large number of transferable embryos, the superovulation step is crucial. To allow the growth of ovarian follicles, the most commonly used protocol consists of 2 intramuscular injections per day over 4 days of a saline solution of the follicle-stimulating hormone. To reduce workload, technical errors in the injected dose and animal stress, different strategies have been investigated to sustain the release of this hormone over 4 days in 1 or 2 injections. This review introduces the physicochemical properties of the follicle-stimulating hormone and discusses the limitations of marketed products and all the research that has been conducted to overcome these limitations. In particular, the field of subcutaneous administrations, the development of new formulations such as viscous solutions, implants and microspheres and the modification of the structure of the follicle-stimulating hormone are overviewed and discussed.

Degradable polymer prodrugs with adjustable activity from drug-initiated radical ring-opening copolymerization.

Degradable polymer prodrugs based on gemcitabine (Gem) as an anticancer drug were synthesized by 'drug-initiated' nitroxide-mediated radical ring-opening copolymerization (NMrROP) of methacrylic esters and 2-methylene-4-phenyl-1,3-dioxolane (MPDL). Different structural parameters were varied to determine the best biological performances: the nature of the monomer [i.e., oligo(ethylene glycol) methacrylate (OEGMA) or methyl methacrylate (MMA)], the nature of the Gem-polymer linker (i.e., amide or amide and diglycolate) and the MPDL content in the copolymer. Depending on the nature of the methacrylate monomer, two small libraries of water-soluble copolymer prodrugs and nanoparticles were obtained (M n ∼10 000 g mol-1, D = 1.1-1.5), which exhibited tunable hydrolytic degradation under accelerated conditions governed by the MPDL content. Drug-release profiles in human serum and in vitro anticancer activity on different cell lines enabled preliminary structure-activity relationships to be established. The cytotoxicity was independently governed by: (i) the MPDL content - the lower the MPDL content, the greater the cytotoxicity; (ii) the nature of the linker - the presence of a labile diglycolate linker enabled a greater Gem release compared to a simple amide bond and (iii) the hydrophilicity of the methacrylate monomer-OEGMA enabled a greater anticancer activity to be obtained compared to MMA-based polymer prodrugs. Remarkably, the optimal structural parameters enabled reaching the cytotoxic activity of the parent (free) drug.