HPMA copolymer-doxorubicin-gadolinium conjugates: synthesis, characterization, and in vitro evaluation

This study describes the synthesis, characterization, and in vitro evaluation of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-gadolinium (Gd)-doxorubicin (Dox) conjugates. Copolymers of HPMA were derivatized to incorporate side chains for Gd chelation and Dox conjugation. The conjugates were characterized by their side chain contents, T(1) relaxivity (r(1)), stability, and in vitro cytotoxicity. High stability and relaxivity of these conjugates coupled with low toxicity show their potential for monitoring the in vivo fate of HPMA-based drug delivery systems by magnetic resonance imaging techniques.     

How the elliptic integrals K and E arise from circles and points in the Minkowski plane

Various self-circumferences of unit circles placed on a Minkowskian plane are expressed in terms of elliptic integrals of the first and second kinds. Landen's transformation is interpreted in this geometric context, and the self-circumferences are estimated asymptotically in the case of circles whose boundaries come very close to the origin.     

Polymeric conjugates for drug delivery

The field of polymer therapeutics has evolved over the past decade and has resulted in the development of polymer-drug conjugates with a wide variety of architectures and chemical properties. Whereas traditional non-degradable polymeric carriers such as poly(ethylene glycol) (PEG) and N-(2-hydroxypropyl methacrylamide) (HPMA) copolymers have been translated to use in the clinic, functionalized polymer-drug conjugates are increasingly being utilized to obtain biodegradable, stimuli-sensitive, and targeted systems in an attempt to further enhance localized drug delivery and ease of elimination. In addition, the study of conjugates bearing both therapeutic and diagnostic agents has resulted in multifunctional carriers with the potential to both "see and treat" patients. In this paper, the rational design of polymer-drug conjugates will be discussed followed by a review of different classes of conjugates currently under investigation. The design and chemistry used for the synthesis of various conjugates will be presented with additional comments on their potential applications and current developmental status.     

Weak and cyclic amenability for Fourier algebras of connected Lie groups

Using techniques of non-abelian harmonic analysis, we construct an explicit, non-zero cyclic derivation on the Fourier algebra of the real ax+b$ax+b$ group. In particular this provides the first proof that this algebra is not weakly amenable. Using the structure theory of Lie groups, we deduce that the Fourier algebras of connected, semisimple Lie groups also support non-zero, cyclic derivations and are likewise not weakly amenable. Our results complement earlier work of Johnson (1994) [15], Plymen (2001) [18] and Forrest, Samei, and Spronk (2009) [9]. As an additional illustration of our techniques, we construct an explicit, non-zero cyclic derivation on the Fourier algebra of the reduced Heisenberg group, providing the first example of a connected nilpotent group whose Fourier algebra is not weakly amenable.     

GRP78‐Targeted HPMA Copolymer‐Photosensitizer Conjugate for Hyperthermia‐Induced Enhanced Uptake and Cytotoxicity in MCF‐7 Breast Cancer Cells

Photodynamic therapy (PDT) is a promising cancer treatment approach. However, the photosensitizers (PS) used for PDT are often limited by their poor solubility and selectivity for tumors. The goal of this study is to improve water solubility and delivery of the photosensitizer 2‐[1‐hexyloxyethyl]‐2‐divinyl pyropheophorbide‐a (HPPH) to breast cancer cells. An N‐(2‐hydroxypropyl)methacrylamide (HPMA) copolymer–HPPH photosensitizer conjugate is synthesized with heat shock receptor glucose‐regulated protein 78 (GRP78), targeting to GRP78 receptors of MCF‐7 cells, which are upregulated under mild hyperthermia. It is found that the uptake of the GRP78 targeted pep‐HPMA‐HPPH copolymer conjugate in MCF‐7 cells is improved through heat induction. Under mild hyperthermia the targeted copolymers are more effective compared to free HPPH. These results show potential for the utility of mild hyperthermia and copolymer delivery vehicles to enhance the efficacy of photodynamic therapy.     

Kinetic studies of nucleophilic substitution of various halothiadiazoles with methoxide ion

A number of halo-substituted 1,2,3 and 1,3,4-thiadiozoles have been prepared, their reactivity towards methoxide ion have been studied and the kinetic parameters are reported.     

Amenability constants for semilattice algebras

For any finite commutative idempotent semigroup S, a semilattice, we show how to compute the amenability constant of its semigroup algebra ℓ ¹(S). This amenability constant is always of the form 4n+1. We then show that these give lower bounds to amenability constants of certain Banach algebras graded over semilattices. We also give example of a commutative Clifford semigroups G _n whose semigroup algebras ℓ ¹(G _n ) admit amenability constants of the form 41+4(n−1)/n. We also show there is no commutative semigroup whose semigroup algebra has an amenability constant between 5 and 9. N. Spronk’s research was supported by NSERC Grant 312515-05.     

N‐(2‐Hydroxypropyl)methacrylamide (HPMA) Copolymer‐Linked Nitroxides: Potential Magnetic Resonance Contrast Agents

N‐(2‐Hydroxypropyl)methacrylamide (HPMA) copolymer‐linked nitroxides were synthesized as macromolecular contrast agents for MR imaging. Molar relaxivities of HPMA copolymer‐linked nitroxides increased linearly in proportion to the number of nitroxides attached per gram of copolymer. HPMA copolymer‐linked nitroxides with 15, 20 and 30 mol‐% nitroxide exhibited higher relaxivities than gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). These results demonstrate the potential of HPMA copolymer‐linked nitroxides as MR contrast agents for solid tumors.

Structure of HPMA copolymer‐linked nitroxides.