Iron Binding and Iron Removal Efficiency of Desferrioxamine Based Polymeric Iron Chelators: Influence of Molecular Size and Chelator Density.

Desferrioxamine (DFO) is a clinically approved, high affinity iron chelator used for the treatment of iron overload. Due to its short half-life and toxicity, DFO is administered for 8-12 h per day, 5-7 d per week. In this manuscript, the influence of molecular properties of hyperbranched polyglycerol (HPG)-DFO conjugates on their iron binding by isothermal titration calorimetry, iron removal efficiency from ferritin in presence and absence of a low molecular weight (MW) iron chelator, and protection against iron mediated oxidation of proteins is reported.

In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator.

Desferrioxamine (DFO) is currently in clinical use to remove iron from transfusion-dependent patients with β-thalassemia major, sickle-cell anemia and the myelodysplastic syndromes. However, its short half-life, burdensome, subcutaneous mode of administration and propensity to cause neurotoxicity at high doses greatly hinder its use. Thus, developing an optimized version of DFO with extended half-life, and reduced toxicity is a major goal.

Clinically approved iron chelators influence zebrafish mortality, hatching morphology and cardiac function.

Iron chelation therapy using iron (III) specific chelators such as desferrioxamine (DFO, Desferal), deferasirox (Exjade or ICL-670), and deferiprone (Ferriprox or L1) are the current standard of care for the treatment of iron overload. Although each chelator is capable of promoting some degree of iron excretion, these chelators are also associated with a wide range of well documented toxicities. However, there is currently very limited data available on their effects in developing embryos.

Hybrid polyglycerols with long blood circulation: synthesis, biocompatibility, and biodistribution.

Multifunctional polymers with defined structure and biocompatibility are critical to the development of drug delivery systems and bioconjugates. In this article, the synthesis, in vitro blood compatibility, cell viability, in vivo circulation, biodistribution, and clearance of hybrid copolymers based on linear and branched polyglycerol are reported. Hybrid polyglycerols (M(n) ≈ 100 kDa) are synthesized with different compositions (15-80 mol% linear polyglycerol).

Design of long circulating nontoxic dendritic polymers for the removal of iron in vivo.

Patients requiring chronic red blood cell (RBC) transfusions for inherited or acquired anemias are at risk of developing transfusional iron overload, which may impact negatively on organ function and survival. Current iron chelators are suboptimal due to the inconvenient mode of administration and/or side effects. Herein, we report a strategy to engineer low molecular weight iron chelators with long circulation lifetime for the removal of excess iron in vivo using a multifunctional dendritic nanopolymer scaffold.

Biodegradable polyglycerols with randomly distributed ketal groups as multi-functional drug delivery systems.

Biodegradable multi-functional polymeric nanostructures that undergo controlled degradation in response to physiological cues are important in numerous biomedical applications including drug delivery, bio-conjugation and tissue engineering. In this paper, we report the development of a new class of water soluble multi-functional branched biodegradable polymer with high molecular weight and biocompatibility which demonstrates good correlation of in vivo biodegradation and in vitro hydrolysis. Main chain degradable hyperbranched polyglycerols (HPG) (20-100 kDa) were synthesized by the introduction of acid labile groups within the polymer structure by an anionic ring opening copolymerization of glycidol with ketal-containing epoxide monomers with different ketal structures.

Influence of architecture of high molecular weight linear and branched polyglycerols on their biocompatibility and biodistribution.

The availability of long circulating, multifunctional polymers is critical to the development of drug delivery systems and bioconjugates. The ease of synthesis and functionalization make linear polymers attractive but their rapid clearance from circulation compared to their branched or cyclic counterparts, and their high solution viscosities restrict their applications in certain settings. Herein, we report the unusual compact nature of high molecular weight (HMW) linear polyglycerols (LPGs) (LPG - 100; M(n) - 104 kg mol(-1), M(w)/M(n) - 1.

Observational analysis of BOA free-papers (2001): from presentation to publication and comparison with the American Academy of Orthopaedic Surgeons (AAOS).

Aim: The objectives of this study were to: determine the presentation to publication conversion rate (PPCR) in peer-reviewed indexed journals of free papers and posters presented at 12-14th September 2001 British Orthopaedic Association (BOA) annual meeting and to compare the publication rate with the American Academy of Orthopaedic Surgeons (AAOS) meeting in 2001.

Methodology: We looked at all presentations including both podium and poster presentations at British Orthopaedic Association meeting held in 2001 and assessed for subsequent publication as full-text article with a fixed PubMed search protocol. Once the abstract was identified as being published, we noted the name of the journal, citation, and time to presentation.

Phase behavior of ketoprofen-poly(lactic acid) drug particles formed by rapid expansion of supercritical solutions.

The present contribution investigates whether it is possible to form stable amorphous particles of ketoprofen-poly(lactic acid), naproxen-poly(lactic acid), and indomethacin-poly(lactic acid). Amorphization and micronization of these poorly water-soluble drugs offer a combined way to improve the solubility and enhance the dissolution rate. The particles were formed by pulsed rapid expansion of supercritical CO(2) solutions and characterized in the aerosol phase with rapid-scan infrared spectroscopy and after collection with scanning electron microscopy and X-ray diffraction.