Peristaltic Pumping of Blood Through Small Vessels of Varying Cross-section

The paper is devoted to a study of the peristaltic motion of blood in the micro-circulatory system. The vessel is considered to be of varying cross-section. The progressive peristaltic waves are taken to be of sinusoidal nature. Blood is considered to be a Herschel-Bulkley fluid. Of particular concern here is to investigate the effects of amplitude ratio, mean pressure gradient, yield stress and the power law index on the velocity distribution, streamline pattern and wall shear stress. On the basis of the derived analytical expression, extensive numerical calculations have been made. The study reveals that velocity of blood and wall shear stress are appreciably affected due to the non-uniform geometry of blood vessels. They are also highly sensitive to the magnitude of the amplitude ratio and the value of the fluid index.Comment: Accepted for publication in ASME journal of Applied Mechanics. arXiv admin note: text overlap with arXiv:1108.1285v

Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts

Liposomal drug delivery enhances the tumour selective localisation and may improve the uptake compared to free drug. However, the drug distribution within the tumour tissue may still be heterogeneous. Degradation of the extracellular matrix is assumed to improve the uptake and penetration of drugs. The effect of the ECM-degrading enzyme hyaluronidase on interstitial fluid pressure and microvascular pressure were measured in human osteosarcoma xenografts by the wick-in-needle and micropipette technique, respectively. The tumour uptake and distribution of liposomal doxorubicin were studied on tumour sections by confocal laser scanning microscopy. The drugs were injected i.v. 1 h after the hyaluronidase pretreatment. Intratumoral injection of hyaluronidase reduced interstitial fluid pressure in a nonlinear dose-dependent manner. Maximum interstitial fluid pressure reduction of approximately 50% was found after injection of 1500 U hyaluronidase. Neither intratumoral nor i.v. injection of hyaluronidase induced any changes in the microvascular pressure. Thus, hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake and improving the distribution of the liposomal doxorubicin. Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, and administration of hyaluronidase adjuvant with liposomal doxorubicin may thus improve the therapeutic outcome