Undifferentiated Profile Research Articles

The Role of Excipients in the Control of Dehydroepiandrosterone Inclusion Complex Delivery

AimThe aim of this study was to develop systems containing dehydroepiandrosterone (DHEA), in the form of an inclusion complex with α-cyclodestrin (c-DHEA), which are able to change the release profile of the hormone according to time and excipient composition.MethodTwenty-five formulations were prepared containing DHEA (prasterone) in the chemical form of an inclusion complex with α-cyclodextrin (57.3% w/w). The drug was mixed with three different excipient systems: the first ‘fast’ one was a mixture of two disintegrants (microcrystalline cellulose and sodium carboxymethyl starch at prefixed 4.15 weight ratio); the second ‘gelling’ excipient contained two gel-forming agents (high viscosity hydroxypropyl methylcellulose and cross-linked polyvinyl pyrrolidone) at three weight ratios: 0.31, 1.00, and 2.45; and the third type of ‘binary’ mixture was prepared by combining ‘fast’ and ‘gelling’ systems at three weight ratios: 1:2, 1:1, and 2:1. Tablets were prepared by direct compression or after wet granulation of these formulations.Results’Fast’ tablets induced a rapid release of the drug while ‘gelling’ tablets were found to modify the release, according to composition. A profile, characterized by an initial phase of rapid drug release, followed by a period of slower release is achieved with series 1:1 tablets. Series 1:2 tablets provide linear release of the drug; while an undifferentiated profile was found for series 2:1 tablets.ConclusionDifferent release mechanisms and the control of drug release were obtained by using DHEA in its inclusion complex and varying the weight ratios of the excipients.

Neuron-glia interactions of rat hippocampal cells in vitro: glial- guided neuronal migration and neuronal regulation of glial differentiation

To examine neuron-glia interactions of hippocampal cells, including glial-guided neuronal migration, glial organization of neuronal positioning and neuronal regulation of astroglial differentiation, rat hippocampal tissue, harvested between embryonic day 16 (E16) and postnatal day 3 (P3), was dissociated into a single cell suspension and plated in glass coverslip microcultures (Hatten and Liem, 1981; Hatten et al., 1984). Immunostaining the cells with antibodies against the glial filament protein (AbGFP) revealed developmental stage-specific changes in the number and extent of morphological differentiation of hippocampal astroglial cells. At E16-E18, fewer than 5% of the cells were AbGFP-positive; stained cells were immature, bearing very short processes. By E19-E20, the number of stained cells increased to 15% of the total cell population. Three forms of differentiated glial cells predominated, a bipolar form bearing processes 30-50 microns, an elongated form which resembled the radial glia of hippocampus, bearing processes 120 microns in length, and a stellate form with 3 or more processes 30-50 microns in length. At P0-P3, glial morphological differentiation varied with the culture substratum; differentiated forms resembling those seen at E20 occurred on Matrigel, but not on polylysine. Quantitation of the distribution of neurons relative to AbGFP-stained glial processes revealed developmental stage-specific changes in glial organization of neuronal positioning in the cultures. In cultures of E16-E18 hippocampal cells, the neurons did not preferentially associate with astroglial cells. By E19-E20, extensive neuron-glia interactions occurred, with 80-90% of the neurons being located within 5-10 microns of a glial process. In addition to their organization of neuronal positioning, E20 hippocampal astroglial cells supported extensive neuronal migration. Migrating hippocampal neurons displayed a cytology and neuron-glia cell apposition identical to that described for migrating cerebellar granule cells in vitro (Edmondson and Hatten, 1987), closely apposing their cell soma against the hippocampal glial process and moving along the glial arm by extending a thickened, leading process. Migration was seen only along highly elongated glial profiles resembling radial glial seen in vivo. The morphological differentiation of hippocampal glial cells in vitro was dependent on cell-cell interactions with neurons. In the absence of neurons, purified hippocampal astroglia had flat, undifferentiated profiles and proliferated rapidly. The addition of hippocampal neurons rapidly arrested glial growth and induced glial process extension.