Cross-linked amylose tablets containing alpha-amylase: an enzymatically-controlled drug release system.

An oral controlled release system based on direct compression of cross-linked amylose (CLA) and drug powders was previously introduced. For drugs with limited solubility or for some drugs for which solubility can be influenced by variation of gastro-intestinal pH, a system is required to accelerate drug release. This paper describes a novel enzymatically-controlled drug release (ECDR) system based on the addition of alpha-amylase to CLA tablets, which can modulate the release kinetics of drugs. The alpha-amylase within the tablets is able to hydrolyze alpha-1-4-glucosidic bonds present in the CLA semisynthetic substrate. Increasing amounts of alpha-amylase (5 to 25 EU) within the tablets induced a significant decrease in release time from 24 to 6 h. High amounts of external alpha-amylase (300-6000 EU/l) had a slight effect on the release rate. Drug release from the ECDR system seems to be controlled by two sequential mechanisms: (a) hydration and swelling of CLA tablets followed by (b) internal enzymatic hydrolysis of the hydrated gel phase.

Image analysis studies of water transport and dimensional changes occurring in the early stages of hydration in cross-linked amylose matrices.

The purpose of this work was to monitor and quantify water transport and dimensional changes occurring in the early stages of hydration in cross-linked amylose (CLA) matrices using image analysis technique. Samples were prepared by direct compression of CLA-6 powder to obtain matrices of 0.17 cm thickness and 1.295 cm in diameter. A surface gel layer was formed quasiinstantaneously. The gel expansion was then constrained and the material continuity caused the outer gel layer to be in a state of biaxial compression and the internal core in a state of biaxial tension. A diffusion front preceded the gel-glass interface even in the early stages of hydration. A delayed stress-release occurred through a radial expansion of the tablet interior. This relaxation coincided with the time at which the axial diffusion fronts met. The dimensional changes had a marked impact on the kinetics of water uptake in CLA-6 tablets in early stages of hydration.

New concepts in the study of tissue vascularization: a mathematical model of skin vascularization.

A preliminary study demonstrated the existence of a fractal structure for perforator arterial vessels of the skin and proved to be a useful tool to compare vascular trees on the basis of their complexity. Fractal analysis of axial-perforator arteriovenous vascular trees was performed on the skin of mice after injection of the arterial network by india ink. Fractal analysis was performed by box counting. Fractal dimension D was determined for 35 venous and 31 arterial perforator vessels (D = 1.302 and 1.264, respectively) and 5 venous and 3 arterial axial vessels (D = 1.374 and 1.328, respectively) (r2 > or = 0.985). All vascular networks show a fractal structure, characterized by a specific D. These values are relatively constant; D is a function of the anatomic and physiologic characteristics. There was no significant difference between venous and arterial networks, nor was there between axial and perforator networks (p < 0.05); this demonstrates a similar efficacy in terms of perfusion of the skin. A computer simulation based on fractal theory has been developed to reproduce the two kinds of vascular networks. Fractals are the result of a construction procedure that is repeated and repeated so that the iteration of a very simple rule can produce seemingly complex shapes, such as vascular networks. The basic module that is repeated in the whole structure is Y-shaped and is termed the generator; this generator is applied to a basic structure, called the initiator. After a few iterations, a vascular network is obtained. The difference between axial and perforator vascular networks is the choice of the initiator, whereas the generator is identical.(ABSTRACT TRUNCATED AT 250 WORDS)

A new approach to the study of skin vascularization.

There are several methods of quantifying the vascularization of tissues, including the skin, but they are imprecise in terms of quantification of the complexity and structure of vascular networks. Fractal analysis can quantify the complexity of any structure existing in nature by using fractional dimension. This study makes a case for this approach by demonstrating the fractal structure of the skin vascular network in the mouse. The skin was removed from the posterior face of the thigh, which is supplied by a musculocutaneous perforator system. Twenty arterial vascular networks were investigated by image analysis and the fractal dimension was determined by the box counting method. Statistical analysis revealed an average mean of fractal dimension D = 1.256 (SD = 0.086), indicating low to intermediate complexity with a narrow distribution of results. D should logically fluctuate within a certain limit, depending on the anatomical structure investigated and its physiological function. These results demonstrate the ability of fractal analysis to quantify the vascular pattern of the skin. Fractal analysis opens a new field of investigation in the study of vascularization patterns and possible vascular modification by different physiological or pathological conditions (flap-delay techniques, tobacco use, diabetes mellitus, classification of diabetic retinopathies).