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.

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.

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

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

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.

Z2-Graded Polynomial Identities for Superalgebras of Block-Triangular Matrices

000 Mathematics Subject Classification: Primary 16R50, Secondary 16W55.

A Representation of Binary Matrices

Христина Костадинова, Красимир Йорджев - В статията се обсъжда представянето на произволна бинарна матрица с помощта на последователност от цели неотрицателни числа. Разгледани са някои предимства и недостатъци на това представяне като алтернатива на стандартното, общоприето представяне чрез двумерен масив. Показано е, че представянето на бинарните матрици с помощта на наредени n-торки от естествени числа води до по-бързи алгоритми и до съществена икономия на оперативна памет. Използуван е апарата на обектно-ориентираното програмиране със синтаксиса и семантиката на езика C++.

Microporous polycaprolactone matrices for drug delivery and tissue engineering:the release behaviour of bioactives having extremes of aqueous solubility

Microporous polycaprolactone (PCL) matrices loaded with hydrophobic steroidal drugs or a hydrophilic drug - pilocarpine hydrochloride - were produced by precipitation casting using solutions of PCL in acetone. The efficiency of steroid incorporation in the final matrix (progesterone (56 %) testosterone (46 %) dexamethasone (80 %)) depended on the nature of the drug initially co-dissolved in the PCL solution. Approximately 90 % w/w of the initial load of progesterone, 85 % testosterone and 50 % dexamethasone was released from the matrices in PBS at 37°C over 8 days. Pilocarpine hydrochloride (PH)-loaded PCL matrices, prepared by dispersion of powder in PCL solution, released 70-90 % of the PH content over 12 days in PBS. Application of the Higuchi model revealed that the kinetics of steroid and PH release were consistent with a Fickian diffusion mechanism with corresponding diffusion coefficients of 5.8 × 10-9 (progesterone), 3.9 × 10 -9 (testosterone), 7.1 × 10-10 (dexamethasone) and 22 × 10-8 cm2/s (pilocarpine hydrochloride). The formulation techniques described are expected to be useful for production of implantable, insertable and topical devices for sustained delivery of a range of bioactive molecules of interest in drug delivery and tissue engineering.

An LP-based inconsistency monitoring of pairwise comparison matrices

A distance-based inconsistency indicator, defined by the third author for the consistency-driven pairwise comparisons method, is extended to the incomplete case. The corresponding optimization problem is transformed into an equivalent linear programming problem. The results can be applied in the process of filling in the matrix as the decision maker gets automatic feedback. As soon as a serious error occurs among the matrix elements, even due to a misprint, a significant increase in the inconsistency index is reported. The high inconsistency may be alarmed not only at the end of the process of filling in the matrix but also during the completion process. Numerical examples are also provided.