In vitro release studies on drugs suspended in non-polar media

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43362/1/11096_2005_Article_BF02273093.pd

Oorspronkelijke Artikelen

Physicochemical theories on the stability of particles against agglomeration, the behaviour of particles at the interface and dissolution appeared to act as powerful tools in predicting the rate controlling steps in the model system used. For such a prediction only basic physicochemical properties of the system involved, which are available in the literature or can easily be measured, have to be known. In the present study not only the primary particle size, but also the agglomeration behaviour and therefore the concentration were important factors, particularly when transport to the interface was the rate-limiting step. But, the initial release rate became independent of particle size and concentration when dissolution at the interface limited the rate. Additives present in low concentrations had a decisive influence on the behaviour of the particles in the suspension and at the interface, and thus on the dissolution rate. The relevance of this model study for the design and development of rectal dosage forms is that an insight has been gained into the basic mechanisms involved in the release of solid substances from an apolar medium. Extrapolation of the results to the in vivo release is speculative, because as stated in the introduction, the in vivo release process was studied only in part and under conditions in many ways different from the in vivo situation. Investigations are in progress to study the spreading of suppositories in vivo and to establish the exact conditions in the rectum after administration of a suppository in order to be able to improve the in vitro simulation of the in vivo situation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43363/1/11096_2005_Article_BF02273168.pd

Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo.

This paper deals with the utility of immunoliposomes for the delivery of doxorubicin (DXR) to human ovarian carcinoma cells in vitro and in vivo. We aimed to investigate whether immunoliposome-mediated targeting of DXR to ovarian cancer cells translates in an enhanced anti-tumour effect compared with that of non-targeted DXR liposomes (lacking the specific antibody). Target cell binding and anti-tumour activity of DXR immunoliposomes were studied in vitro and in vivo (xenograft model of ovarian carcinoma). In vitro we observed that target cell binding and cell growth inhibition of DXR immunoliposomes is superior to that of non-targeted DXR-liposomes. However, in vivo, despite the efficient target cell binding and good anti-tumour response of DXR-immunoliposomes, no difference in anti-tumour effect, compared with non-targeted DXR-liposomes, could be determined. The results indicate that premature DXR leakage from immunoliposomes occurring before the actual target cell binding and subsequent DXR association with the tumour cells, explains why no significant differences in anti-tumour activity between DXR-immunoliposomes and non-targeted DXR-liposomes were observed in vivo

Tutorial applications for Verification, Validation and Uncertainty Quantification using VECMA toolkit

The VECMA toolkit enables automated Verification, Validation and Uncertainty Quantification (VVUQ) for complex applications that can be deployed on emerging exascale platforms and provides support for software applications for any domain of interest. The toolkit has four main components including EasyVVUQ for VVUQ workflows, FabSim3 for automation and tool integration, MUSCLE3 for coupling multiscale models and QCG tools to execute application workflows on high performance computing (HPC). A more recent addition to the VECMAtk is EasySurrogate for various types of surrogate methods. In this paper, we present five tutorials from different application domains that apply these VECMAtk components to perform uncertainty quantification analysis, use surrogate models, couple multiscale models and execute sensitivity analysis on HPC. This paper aims to provide hands-on experience for practitioners aiming to test and contrast with their own applications

Stabilization of Peptide Vesicles by Introducing Inter-Peptide Disulfide Bonds

PURPOSE: Previously, we have shown that the amphiphilic oligopeptide SA2 (Ac-Ala-Ala-Val-Val-Leu-Leu-Leu-Trp-Glu-Glu-COOH) spontaneously self-assemble into nano-sized vesicles in aqueous environment. Relative weak individual intermolecular interactions dominate such oligopeptide assemblies. In this study we aimed at improving the stability of such peptide vesicles by covalently crosslinking the oligopeptide vesicles using disulfide bonds. Two and three cysteines were introduced in the SA2 peptide sequence to allow crosslinking (Ac-Ala-Cys-Val-Cys-Leu-(Leu/Cys)-Leu-Trp-Glu-Glu-COOH). RESULTS: Upon disulfide formation the crosslinked vesicles remained stable under conditions that disrupted the non-crosslinked peptide vesicles. The stabilized vesicles were more closely examined in terms of particle size (distribution) using atomic force microscopy, cryogenic electron microscopy, as well as dynamic light scattering analysis, showing an average particle radius in number between 15 and 20 nm. Using entrapment of calcein it was shown that intermolecular crosslinking of peptides within the vesicles did not affect the permeability for calcein. CONCLUSION: Introduction of cysteines into the hydrophobic domain of the SA2 amphiphilic oligopeptides is a feasible strategy for crosslinking the peptide vesicles. Such small crosslinked oligopeptide vesicles may hold promise for drug delivery applications