Chemotherapy can destroy tumors and arrest cancer progress. Unfortunately, severe side effects (treatment is usually a series of injections of highly toxic drugs) often restrict the frequency and size of dosages, much to the detriment of tumor inhibition. Most chemotherapeutic drugs have pharmacokinetic profiles with tremendous potential for improvement. Water-soluble polymers offer the potential to increase drug circulation time, improve drug solubility, prolong drug residence time in a tumor, and reduce toxicity. Cytotoxic drugs that are covalently attached to water-soluble polymers via reversible linkages more effectively target tumor tissue than the drugs alone. Macromolecules passively target solid tumor tissue through a combination of reduced renal clearance and exploitation of the enhanced permeation and retention (EPR) effect, which prevails for fast-growing tumors. Effective drug delivery involves a balance between (i) elimination of the polymeric drug conjugate from the bloodstream by the kidneys, liver, and other organs and (ii) movement of the drug out of the blood vasculature and into the tumor (that is, extravasation). Polymers are eliminated in the kidney by filtration through pores with a size comparable to the hydrodynamic diameter of the polymer; in contrast, the openings in the blood vessel structures that traverse tumors are an order of magnitude greater than the diameter of the polymer. Thus, features that may broadly be grouped as the "molecular architecture" of the polymer, such as its hydrodynamic volume (or molecular weight), molecular conformation, chain flexibility, branching, and location of the attached drug, can greatly impact elimination of the polymer from the body through the kidney but have a much smaller effect on the extravasation of the polymer into the tumor. Molecular architecture can in theory be adjusted to assert essentially independent control over elimination and extravasation. Understanding how molecular architecture affects passage of a polymer through a pore is therefore essential for designing polymer drug carriers that are effective in passively delivering a drug payload while conforming to the requirement that the polymers must eventually be eliminated from the body. In this Account, we discuss examples from in vivo studies that demonstrate how polymer architectural features impact the renal filtration of a polymer as well as tumor penetration and tumor accumulation. In brief, features that inhibit passage of a polymer through a pore, such as higher molecular weight, decreased flexibility, and an increased number of polymer chain ends, help prevent elimination of the polymer by the kidneys and can improve blood circulation times and tumor accumulation, thus improving therapeutic effectiveness.

/pdf/soluble-polymer-carriers-for-the-treatment-of-cancer-the-3mxk5qjuly.pdf

Soluble polymer carriers for the treatment of cancer: The importance of molecular architecture

PROBLEM TO BE SOLVED: To perform molecular weight measurement and separation of a fluorine containing organic substance slightly soluble in a general organic solvent by means of size exclusion chromatography by using a solvent containing dichloro pentafluoropropane as a mobile phase and using polymethyl methacrylate with a known molecular weight as a molecular weight measurement standard specimen. SOLUTION: As a mobile phase. a solvent containing HCFC225 such as a solvent containing only HCFC225 and a mixture solvent containing HCFC225 and other solvents are available. HCFC225 is selected from one or more kinds of substances selected from chlorinated fluorinated hydrocarbons with a molecular formula represented by C3 HF3 Cl2 . As the HCFC225, several kinds of isomers with the same molecular formula and different structures are known, however, HCFC225ca (CF3 CF2 CHCl2 ), HCFC225cb (CF2 ClCF2 CFHC1), and a mixture of them are desirable. As a molecular weight measurement standard specimen, polymethyl methacrylate with a known molecular weight is used.

https://www.springer.com/productFlyer_978-3-540-65635-7.pdf?SGWID=0-0-1297-1427978-0

Size Exclusion Chromatography

Block and graft copolymer micelles in solution

Materials with a ribbon- or ladder-type framework possess a two-dimensional geometry and are thus intermediate between linear and three-dimensional systems. The limited conformational freedom of ladder polymers is particularly relevant in the case of conjugated ladder-type materials since the steric inhibition of electron delocalization is drastically reduced.Up until today two general routes have been used to prepare ladder-type materials: (1) the polymerisation of multifunctional monomers, in which both strands of the ladder structure are generated in a single reaction; and (2) the cyclisation of suitably functionalized open-chain (single-stranded) precursor polymers in a polymer-analogous process. Both strategies pre-suppose certain essentials to arrive at structurally defined ladder polymers, especially the exclusion of side-reactions and an almost quantitative conversion of the starting materials.The main attention of this article is focused on an active physical function of ladder-type materials. Among others, ladder-type poly( p-phenylene)s (LPPPs) represent an outstanding class of ladder-type materials. They are characterized by an extraordinarily low concentration of active traps (topological defects, impurities) and display a set of attractive electronic properties (very intensive photo- and electroluminescence, high charge carrier mobilities). This unique performance has established the solution processable LPPPs as standard materials for organic polymer based light emitting diodes (LEDs) and optically pumped solid state lasers.

Ladder-type materials

The intrinsic viscosity of biological macromolecules. Progress in measurement, interpretation and application to structure in dilute solution.

The Influence of Solvents on Unperturbed Dimensions of Polymer in Solution

Etude du comportement d'une série de polystyrènes linéaires dans des mélanges de solvants

Linear representation of viscosity data as a function of molecular weight

A very sharp crossover is observed in the variation of the reduced viscosity ηsp/c as a function of the concentration c for mixtures of 1:1 by weight mixtures of polystyrene and poly(methylmethacrylate) in benzene at 20°C and a 1:1 by weight mixture of poly(ethylene glycol) and polystyrene in benzene at 20°C. The crossover is attributed to the critical to the concentration of the two respective polymers in the solution and its sharpness is due to the incompatibility between the two different polymers.

Anastasios Dondos

Papers

The Influence of Solvents on Unperturbed Dimensions of Polymer in Solution

Etude du comportement d'une série de polystyrènes linéaires dans des mélanges de solvants

Linear representation of viscosity data as a function of molecular weight

Hydrodynamic crossover in two‐polymer mixtures from viscosity measurements

Viscometric study of aggregation phenomena in polymer dilute solutions and determination of the critical concentration c