Biomedical subjects

A Goepferich

Publications and source records attributed to A Goepferich.

6 recordsLinked to original sources

PubMed2006

Programmable implants--from pulsatile to controlled release.

The aim of this study was to develop programmable implants with a reproducible delayed onset of release followed by several weeks of controlled release. For this purpose, a drug-loaded core was embedded into a drug-free bulk-eroding poly(D,L lactic-co-glycolic acid) or poly(D,L lactic acid) mantle. The manufacturing procedure was established and optimized for three mantle materials, which showed delay times ranging from 7 to 83 days. Triglycerides with fatty acid chain lengths from C12 to C18 were investigated as core materials, producing release periods from 2 to 16 weeks. Concomitantly, applying a convolution/deconvolution model showed the possibility of theoretical prediction of the resulting release profiles.

Arylsulfonates↗

PubMed2006

Biocompatibility and erosion behavior of implants made of triglycerides and blends with cholesterol and phospholipids.

Triglycerides are a promising class of material for the parenteral delivery of drugs and have become the focus of tremendous research efforts in recent years. The aim of this study was to investigate the biocompatibility of glyceroltripalmitate as well as the influence of cholesterol and distearoyl-phosphatidyl-choline (DSPC) on the erosion behavior of the lipid. For these investigations, two in vivo studies were carried out, in which cylindrical matrices of 2 mm diameter were manufactured and subcutaneously implanted in immunocompetent NMRI-mice. After excision of the implants, tissue reactions of the animals as well as changes in the weight, shape and microstructure of the implants were investigated. The triglyceride and cholesterol showed good biocompatibility, as indicated by their minimal encapsulation in connective tissue and the absence of inflammatory reactions. Increasing the levels of phospholipid in the implants, however, led to an increased inflammatory reaction. In contrast to cholesterol, which did not affect erosion, the incorporation of DSPC into the triglyceride matrices led to clearly visible signs of degradation.

Animals↗

PubMed2006

In vitro investigation of lipid implants as a controlled release system for interleukin-18.

Operating on the inductive and effective phases of an anti-tumor immune response and uncovering pivotal functions that may reduce cancer cell growth, interleukin-18 (IL-18) appears to be an attractive candidate for the sustained local adjuvant immunotherapeutic treatment of brain gliomas. The objective of this work was to develop IL-18 loaded lipid implants as a controlled delivery system. For the preparation of protein loaded triglyceride matrix material, a solid-in-oil (s/o) dispersion technique was chosen for which protein particles in the micrometer range were first prepared by co-lyophilization with polyethylene glycol (PEG). Implants of 1 mm diameter, 1.8 mm height and 1.8 mg weight were manufactured by compression of the powder mixture in a specially designed powder compacting tool. The in vitro release behavior of 125I-Bolton-Hunter-radiolabeled IL-18 was assessed in a continuous-flow system. A cell culture assay was established for the determination of bioactivity of released IL-18. Implants showed a continuous release of 10-100 ng IL-18 per day for 12 days. A progressive integrity loss was observed with ongoing release, which would be related to protein degradation during incubation. The initially released fraction proved complete retention of bioactivity, indicating that the manufacturing procedure had no detrimental effects on protein stability.

Animals↗

PubMed2006

Drug release from lipid-based implants: elucidation of the underlying mass transport mechanisms.

The aim of this study was to better understand the mass transport mechanisms involved in the control of drug release from lipid-based implants. Different types of triglyceride-based cylinders were prepared by compression. Glycerol-trilaurate, -trimyristate, -tripalmitate and -tristearate were used as model lipids, lysozyme and pyranine as model drugs. The effects of several formulation and processing parameters on the resulting drug release kinetics in phosphate buffer pH 7.4 were studied and the obtained results analyzed using Fick's second law of diffusion. Interestingly, lysozyme release from implants prepared by compression of a lyophilized emulsion (containing dissolved drug and lipid) was found to be purely diffusion-controlled, irrespective of the type of triglyceride. In contrast, the dominating release mechanism depended on the type of lipid in the case of pyranine-loaded implants prepared by compression of a lyophilized lipid-drug solution: with glycerol-trilaurate and -tristearate the systems were found to be purely diffusion-controlled, whereas also other mass transport phenomena are of importance in glycerol-trimyristate and -tripalmitate-based devices. Similarly, changes in the size of the compressed lipid-drug particles, drug loading and compression force significantly affected the underlying release mechanisms. The addition of a drug-free, poly(lactic-co-glycolic acid) (PLGA)-based coating around the implants delayed the onset of pyranine release for about 20 days. Interestingly, the subsequent drug release was purely diffusion-controlled, irrespective of the type of triglyceride. Also the addition of different amounts (and particle size fractions) of saccharose to pyranine-loaded implants led to purely diffusion-controlled drug release.

Arylsulfonates↗

PubMed2006

Paclitaxel-loaded microparticles and implants for the treatment of brain cancer: preparation and physicochemical characterization.

The aim of this study was to prepare different types of paclitaxel-loaded, PLGA-based microparticles and lipidic implants, which can directly be injected into the brain tissue. Releasing the drug in a time-controlled manner over several weeks, these systems are intended to optimize the treatment of brain tumors. The latter is particularly difficult because of the blood-brain barrier (BBB), hindering most drugs to reach the target tissue upon systemic administration. Especially paclitaxel (being effective for the treatment of ovarian, breast, lung and other cancers) is not able to cross the BBB to a notable extent since it is a substrate of the efflux transporter P-glycoprotein. Both, biodegradable microparticles as well as small, cylindrical, glycerol tripalmitate-based implants (which can be injected using standard needles) were prepared with different paclitaxel loadings. The effects of several formulation and processing parameters on the resulting drug release kinetics were investigated in phosphate buffer pH 7.4 as well as in a diethylnicotinamide (DENA)/phosphate buffer mixture. Using DSC, SEM, SEC and optical microscopy deeper insight into the underlying drug release mechanisms could be gained. The presence of DENA in the release medium significantly increased the solubility of paclitaxel, accelerated PLGA degradation, increased the mobility of the polymer and drug molecules and fundamentally altered the geometry of the systems, resulting in increased paclitaxel release rates.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Bone morphogenetic protein 9: a potent modulator of cartilage development in vitro.

Few publications describe the activity of bone morphogenetic protein-9 (BMP-9), but the consensus of these largely in vivo studies is that while BMP-9 can induce ectopic bone formation at relatively large concentrations, it is primarily active in non-skeletal locations--including the liver, nervous system and marrow. To study the effects of BMP-9 on chondrogenesis in a well-defined environment, calf articular chondrocytes were seeded onto biodegradable PGA scaffolds. The resulting cell-polymer constructs were cultured in either control medium or medium supplemented with 1, 10, 50 or 100 ng/ml of BMP-9. After 4 weeks of in vitro culture, all concentrations of BMP-9 increased the total mass of the constructs, and the amounts of collagen, glycosaminoglycans (GAG) and cells per construct. On a mass percentage basis, BMP-9 tended to increase GAG, to decrease the relative amount of collagen and had little effect on the relative amount of cells. BMP-9 elicited qualitatively similar responses as BMP-2, -12 and -13. However, in contrast to BMP-12 and -13, BMP-9 (at concentrations > or = 10 ng/ml) induced hypertrophic chondrocyte formation and was the only BMP tested to induce mineralization. Taken together, these data suggest that BMP-9 is a potent modulator of cartilage development in vitro.

Alkaline Phosphatase↗