Biomedical subjects

M J Schaefer

Publications and source records attributed to M J Schaefer.

15 recordsLinked to original sources

PubMed2001

Effect of additives on stability of etoposide in PLGA microspheres.

The purpose of this article was to determine the shelf life of etoposide in poly(lactic-co-glycolic acid) (PLGA) microspheres prepared with and without additives (i.e., tricaprin and isopropyl myristic acid ester [IPM]). The microspheres were prepared by a single-emulsion solvent extraction technique with and without 25% w/w additive. The batches of microspheres were subjected to an accelerated stability study at two elevated temperatures (70 degrees C and 80 degrees C or 80 degrees C and 90 degrees C). Samples were taken at 7, 14, 21, 28, and 35 days for estimation of drug content by high-performance liquid chromatography (HPLC). The drug stability in the microspheres was determined by plotting the log percentage drug remaining versus time to obtain the degradation rate constant k of etoposide at the measured temperature. This degradation rate constant was then used in the Arrhenius equation to obtain the activation energy of etoposide, which was utilized to determine the shelf life of the microspheres at room temperature. The results showed that all three microsphere formulations had good long-term stability at room temperature (6.62-8.86 years at 25 degrees C). The plain microspheres were shown to possess a shelf life of 6.62 years, and the IPM and tricaprin were the most stable with shelf lives of 8.25 and 8.86 years, respectively.

Antineoplastic Agents, Phytogenic↗

PubMed2000

Effect of isopropyl myristic acid ester on the physical characteristics and in vitro release of etoposide from PLGA microspheres.

The purpose of this paper was to study the effect of the isopropyl myristic acid ester (IPM) on the physicochemical characteristics of etoposide-loaded poly(lactic-co-glycolic acid) (PLGA) microspheres-specifically, the effects on the size and drug loading of the microspheres, the polymer matrix and surface morphology, and the release of etoposide from the microspheres. The experiment was structured to examine 2 IPM concentrations (25% and 50%) and 1 control (no IPM) at 2 different etoposide-loading percentages (10% and 5%). The microspheres were prepared using a single-emulsion solvent-extraction procedure. Samples from each batch of microspheres were then analyzed for size distribution, drug-loading efficiency, surface characteristics, in vitro release, and in vitro microsphere degradation. The incorporation of 50% IPM significantly increased (P <.05) the size of the microspheres when compared with the control and 25% IPM microspheres. However, incorporation of 25% or 50% IPM did not change (P >.05) the drug-loading efficiency in comparison with the microspheres prepared without IPM. The microspheres containing 50% IPM were shown to significantly increase (P <.05) the release of etoposide from the microspheres at both etoposide concentrations. The microspheres prepared incorporating 25% IPM and 5% etoposide increased the in vitro release (P <.05) in comparison with the microspheres prepared without IPM. The 5% etoposide-PLGA microspheres showed a smooth, nonporous surface that changed to a dimpled, nonporous surface after addition of 25% IPM. During the in vitro degradation study, the IPM-containing microspheres slowly became porous but retained their structural integrity throughout the experiment.

Delayed-Action Preparations↗

PubMed2000

Tetrapeptide derivatives of [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) lacking an N-terminal tyrosine residue are agonists at the mu-opioid receptor.

The Phe(1) cyclic tetrapeptide Phe-c[D-Cys-Phe-D-Pen]NH(2) (Et) (JH-54) has been shown previously to exhibit high affinity and selectivity for the mu-opioid receptor. To examine the role of the Phe(1) residue in the unexpected high affinity of this peptide, 11 analogs of JH-54 have been synthesized and evaluated for opioid ligand binding and for efficacy using the [(35)S]GTPgammaS assay. Alteration of the bridging groups between the D-Cys(2) and D-Pen(4) residues of JH-54 from dithioether to disulfide revealed the importance of the relative position of the aromatic rings of the first and third residues in determining mu- and delta-affinities. The one carbon distance between the alpha carbon and phenyl ring in the N-terminal residue was critical. Additional steric bulk in the N-terminal Phe(1) residue was accommodated without large reductions in affinity in two naphthyl analogs, but not with 3, 3-(diphenyl)alanine. Conformational restriction of the Calpha-Cbeta and/or Cbeta-Cgamma bonds had little effect on affinities in two peptides with 2-amino-2-carboxytetralin in position 1, but it abolished activity in an isoquinoline analog and differentially altered activity in four phenylproline(1)-containing peptides. Most surprisingly, replacement of the Phe(1) aromatic ring with cyclohexyl resulted in a peptide of moderate affinity (K(i) = 32.5 nM) and potency (EC(50) = 58.8 nM). Thus, the tyrosyl para-hydroxyl substituent and even aromaticity in the N-terminal amino acid of these tetrapeptides are shown to be important, but not critical, features for mu-opioid receptor affinity, agonist potency, and efficacy.

Animals↗

PubMed1980

An integrated approach to developing administrators and organizations.

Can administrators increase their administrative capabilities in isolation from the rest of the institution? The authors of this article contend that administrative competency can be defined only in terms of contributions to organizational performance and that the motivation to achieve a high level of competency must be supported and reinforced at the institutional level. They establish a basis for the interdependency of administrators and institutions and outline an approach to their simultaneous development.

Administrative Personnel↗

PubMed1978