The controlled release of macromolecules from macroporous hydrophyllic polymer matrices

This work has used novel polymer design and fabrication technology to generate bead form polymer based systems, with variable, yet controlled release properties, specifically for the delivery of macromolecules, essentially peptides of therapeutic interest. The work involved investigation of the potential interaction between matrix ultrastructural morphology, in vitro release kinetics, bioactivity and immunoreactivity of selected macromolecules with limited hydrolytic stability, delivered from controlled release vehicles. The underlying principle involved photo-polymerisation of the monomer, hydroxyethyl methacrylate, around frozen ice crystals, leading to the production of a macroporous hydrophilic matrix. Bead form matrices were fabricated in controllable size ranges in the region of 100µm - 3mm in diameter. The initial stages of the project involved the study of how variables, delivery speed of the monomer and stirring speed of the non solvent, affectedthe formation of macroporous bead form matrices. From this an optimal bench system for bead production was developed. Careful selection of monomer, solvents, crosslinking agent and polymerisation conditions led to a variable but controllable distribution of pore sizes (0.5 - 4µm). Release of surrogate macromolecules, bovine serum albumin and FITC-linked dextrans, enabled factors relating to the size and solubility of the macromolecule on the rate of release to be studied. Incorporation of bioactive macromolecules allowed retained bioactivity to be determined (glucose oxidase and interleukin-2), whilst the release of insulin enabled determination of both bioactivity (using rat epididymal fat pad) and immunoreactivity (RIA). The work carried out has led to the generation of macroporous bead form matrices, fabricated from a tissue biocompatible hydrogel, capable of the sustained, controlled release of biologically active peptides, with potential use in the pharmaceutical and agrochemical industries.

The durability of glass fibre reinforced cements made with new cementitious matrices

Widespread use of glass fibre reinforced cement (GRC) has been impeded by concerns over its durability. Three degradation mechanisms are proposed - fibre corrosion, Ca(OHh precipitation and matrix densification - although their relative importance is debated. Matrices with reduced alkalinities and Ca(OH)2 contents are being developed; the aim of this study was to investigate their hydration and interaction with alkali-resistant fibres to determine the factors controlling their long-term durability, and assess the relevancy of accelerated ageing. The matrices studied were: OPC/calcium-sulphoaluminate cement plus metakaolin (C); OPC plus metakaolin (M); blast-furnace slag cement plus a micro-silica based additive (D); and OPC (O). Accelerated ageing included hot water and cyclic regimes prior to tensile testing. Investigations included pore solution expression, XRD, DTA/TG, SEM and optical petrography. Bond strength was determined from crack spacings using microstructural parameters obtained from a unique image analysis technique. It was found that, for the new matrices - pore solution alkalinities were lower; Ca(OH)2 was absent or quickly consumed; different hydrates were formed at higher immersion temperatures; degradation under 65°C immersion was an order of magnitude slower, and no interfilamental Ca(OH)2 was observed .It was concluded that: fibre weakening caused by flaw growth was the primary degradation mechanism and was successfully modelled on stress corrosion/static fatigue principles. OPC inferiority was attributed partly to its higher alkalinity but chiefly to the growth of Ca(OH)2 aggravating the degradation; and hot water ageing although useful in model formulation and contrasting the matrices, changed the intrinsic nature of the composites rather than simply accelerating the degradation mechanisms.

Spectra of modular and small-world matrices

We compute spectra of symmetric random matrices describing graphs with general modular structure and arbitrary inter- and intra-module degree distributions, subject only to the constraint of finite mean connectivities. We also evaluate spectra of a certain class of small-world matrices generated from random graphs by introducing shortcuts via additional random connectivity components. Both adjacency matrices and the associated graph Laplacians are investigated. For the Laplacians, we find Lifshitz-type singular behaviour of the spectral density in a localized region of small |?| values. In the case of modular networks, we can identify contributions of local densities of state from individual modules. For small-world networks, we find that the introduction of short cuts can lead to the creation of satellite bands outside the central band of extended states, exhibiting only localized states in the band gaps. Results for the ensemble in the thermodynamic limit are in excellent agreement with those obtained via a cavity approach for large finite single instances, and with direct diagonalization results.

Statnote 31:analysis of covariance

Analysis of covariance (ANCOVA) is a useful method of ‘error control’, i.e., it can reduce the size of the error variance in an experimental or observational study. An initial measure obtained before the experiment, which is closely related to the final measurement, is used to adjust the final measurements, thus reducing the error variance. When this method is used to reduce the error term, the X variable must not itself be affected by the experimental treatments, because part of the treatment effect would then also be removed. Hence, the method can only be safely used when X is measured before an experiment. A further limitation of the analysis is that only the linear effect of Y on X is being removed and it is possible that Y could be a curvilinear function of X. A question often raised is whether ANCOVA should be used routinely in experiments rather than a randomized blocks or split-plot design, which may also reduce the error variance. The answer to this question depends on the relative precision of the difference methods with reference to each scenario. Considerable judgment is often required to select the best experimental design and statistical help should be sought at an early stage of an investigation.

Precipitation casting of drug-loaded microporous PCL matrices:incorporation of progesterone by co-dissolution

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37°C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 μg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37°C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices.

Delivery of the antibiotic gentamicin sulphate from precipitation cast matrices of polycaprolactone

Microporous, poly(ε-caprolactone) (PCL) matrices were loaded with the aminoglycoside antibiotic, gentamicin sulphate (GS) using the precipitation casting technique by suspension of powder in the PCL solution prior to casting. Improvements in drug loading from 1.8% to 6.7% w/w and distribution in the matrices were obtained by pre-cooling the suspension to 4°C. Gradual release of approximately 80% of the GS content occurred over 11 weeks in PBS at 37°C and low amounts of antibiotic were measured up to 20 weeks. The kinetics of release could be described effectively by the Higuchi model with the diffusion rate constant (D) increasing from of 1.7 to 5.1 μg/mg matrix/day0.5 as the drug loading increased from 1.4% to 8.3% w/w. GS-loaded PCL matrices retained anti-bacterial activity after immersion in PBS at 37°C over 14 days as demonstrated by inhibition of growth of S. epidermidis in culture. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of hydrophilic molecules such as anti-bacterial agents from implanted, inserted or topical devices. © 2005 Elsevier B.V. All rights reserved.

Numerical implementation of low-PMD spun fibres with precomputed M(w) matrices

Poster With the use of the coarse-step method for simulating the phenomenon of PMD the fibre-twist as not included into the equations. This was an obstacle in representing low-PMD spun fibres numerially.

Parallel Class Intersection Matrices of Orthogonal Resolutions

This work was partially supported by the Bulgarian National Science Fund under Contract No MM 1405. Part of the results were announced at the Fifth International Workshop on Optimal Codes and Related Topics (OCRT), White Lagoon, June 2007, Bulgaria

Primitive Ideals and Symplectic Leaves of Quantum Matrices

It is proved that there exists a bijection between the primitive ideals of the algebra of regular functions on quantum m × n-matrices and the symplectic leaves of associated Poisson structure.

Exponents of Subvarieties of Upper Triangular Matrices over Arbitrary Fields are Integral

Partially supported by grant RFFI 98-01-01020.

On a Five-Diagonal Jacobi Matrices and Orthogonal Polynomials on Rays in the Complex Plane

∗ Partially supported by Grant MM-428/94 of MESC.

Fermat's Equation in Matrices

The Fermat equation is solved in integral two by two matrices of determinant one as well as in finite order integral three by three matrices.

Description Reduction for Restricted Sets of (0,1) Matrices

* The research is supported partly by INTAS: 04-77-7173 project, http://www.intas.be

Algorithmic Minimization of Non-zero Entries in 0,1-Matrices

In this paper we present algorithms which work on pairs of 0,1- matrices which multiply again a matrix of zero and one entries. When applied over a pair, the algorithms change the number of non-zero entries present in the matrices, meanwhile their product remains unchanged. We establish the conditions under which the number of 1s decreases. We recursively define as well pairs of matrices which product is a specific matrix and such that by applying on them these algorithms, we minimize the total number of non-zero entries present in both matrices. These matrices may be interpreted as solutions for a well known information retrieval problem, and in this case the number of 1 entries represent the complexity of the retrieve and information update operations.

Technology of Classification of Electronic Documents Based on the Theory of Disturbance of Pseudoinverse Matrices

Technology of classification of electronic documents based on the theory of disturbance of pseudoinverse matrices was proposed.