Permeability of Interstitial Space of Muscle (Rat Diaphragm) to Solutes of Different Molecular Weights

Schultz, Jerome S.; Armstrong, William D.

doi:10.1002/jps.2600670534

Cited by 31 publications

(14 citation statements)

References 17 publications

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“…Subsequent microscopic inspections of tumors established the higher tumor cell density and tumor-to-stroma ratio in xenograft tumors. This finding, in view of the known quantitative relationships between diffusion coefficient of a molecule with interstitial space (ψ) and tortuosity ( T ) in a gel structure, as shown in Equation 1 (71) , indicated that drug penetration into tumor tissue is highly dependent on the tissue structure and tissue composition, and further suggested the abrupt change in transport kinetics at 24 h was due to a time-dependent change in tumor structure/composition caused by the paclitaxel-induced apoptosis that occurs with a 24 h lag time (72,73,74,75,76,77,78) .…”

Section: Aproaches To Improve Interstitial Transportmentioning

confidence: 67%

Improving Delivery and Efficacy of Nanomedicines in Solid Tumors: Role of Tumor Priming

Wang

Gao

et al. 2011

Nanomedicine

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Effectiveness of nanomedicines in cancer therapy is limited in part by inadequate delivery and transport in tumor interstitium. This report reviews the experimental approaches to improve nanomedicines delivery and transport in solid tumors. These approaches include tumor vasculature normalization, interstitial fluid pressure modulation, enzymatic extracellular matrix degradation, and apoptosis-inducing tumor priming technology. We advocate the latter approach due to its ease and practicality (accomplished with standard-of-care chemotherapy such as paclitaxel) and tumor selectivity. Examples of applying tumor priming to deliver nanomedicines and to design drug/RNAi-loaded carriers are discussed.

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Section: Aproaches To Improve Interstitial Transportmentioning

confidence: 67%

Improving Delivery and Efficacy of Nanomedicines in Solid Tumors: Role of Tumor Priming

Wang

Gao

et al. 2011

Nanomedicine

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“…doxorubicin), w is the effective volume fraction occupied by interstitial space, s is the tortuosity factor, and q is the blood flow rate. With literature values of 0.04 for w/s (38,39), and 55 mL/min/100 g for q (40), the half width for doxorubicin in the prostate was calculated to be 0.15 mm. This value is within 4-fold of the experimentally determined value of 0.53 mm in the bladder wall (28).…”

Section: Discussionmentioning

confidence: 99%

Intraprostatic Chemotherapy: Distribution and Transport Mechanisms

Wientjes

Zheng²,

Hu³

et al. 2005

Clinical Cancer Research

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Purpose:The present study evaluated the tissue distribution and targeting advantage of intraprostatic chemotherapy. Experimental Design: We studied the delivery and spatial distribution of a fluorescent drug, doxorubicin, in the prostate of beagle dogs, after intraprostatic or i.v. administration. Drug concentrations were measured using high-performance liquid chromatography and confocal fluorescence microscopy. Results: I.v. and intraprostatic injections yielded qualitatively and quantitatively different doxorubicin distribution in the prostate. A relatively homogeneous distribution was found after i.v. administration, whereas intraprostatic injection yielded a highly heterogeneous distribution with >10-fold higher concentrations localized in a cone-shaped glandular lobule bound by fibromuscular stroma, compared with other parts of the prostate. Compared with i.v. injection, intraprostatic injection yielded, on average, f100-fold higher tissue-to-plasma concentration ratio, ranging from 963-fold near the injection site to 19-fold in the contralateral half of the prostate. The drug distribution within the prostate further suggests an important role for acinar flow in intraprostatic drug transport. Conclusions: Intraprostatic administration represents a viable option to deliver high drug concentrations within the prostate. The results further suggest the fibromuscular stroma separating the prostatic lobules as a major barrier to drug transport and convective flow as an important drug transport mechanism in the prostate.

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“…where D eff,i is the effective solute diffusivity of the tissue, D i is the diffusivity of solute i in the space available to the solute, i is the fraction of tissue available to solute i (for water-soluble solutes, this would be the interstitial space), and i is the tortuosity of the space to solute i (equal to the ratio of the true path length between 2 points to the linear distance between the 2 points, ϳ2.5 for muscle) (94). For water-soluble substances, both i and i are dependent on the magnitude of interstitial pressure and the makeup of the interstitial matrix (59).…”

Section: Interstitial Matrixmentioning

confidence: 99%

The transport barrier in intraperitoneal therapy

Flessner

2005

American Journal of Physiology-Renal Physiology

202

172

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The peritoneal cavity is important in clinical medicine because of its use as a portal of entry for drugs utilized in regional chemotherapy and as a means of dialysis for anephric patients. The barrier between the therapeutic solution in the cavity and the plasma does not correspond to the classic semipermeable membrane but instead is a complex structure of cells, extracellular matrix, and blood microvessels in the surrounding tissue. New research on the nature of the capillary barrier and on the orderly array of extracellular matrix molecules has provided insights into the physiological basis of osmosis and the alterations in transport that result from infusion of large volumes of fluid. The anatomic peritoneum is highly permeable to water, small solutes, and proteins and therefore is not a physical barrier. However, the cells of the mesothelium play an essential role in the immune response in the cavity and produce cytokines and chemokines in response to contact with noncompatible solutions. The process of inflammation, which depends on the interaction of mesothelial, interstitial, and endothelial cells, ultimately leads to angiogenesis and fibrosis and the functional alteration of the barrier. New animal models, such as the transgenic mouse, will accelerate the discovery of methods to preserve the functional peritoneal barrier.

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Permeability of Interstitial Space of Muscle (Rat Diaphragm) to Solutes of Different Molecular Weights

Cited by 31 publications

References 17 publications

Improving Delivery and Efficacy of Nanomedicines in Solid Tumors: Role of Tumor Priming

Improving Delivery and Efficacy of Nanomedicines in Solid Tumors: Role of Tumor Priming

Intraprostatic Chemotherapy: Distribution and Transport Mechanisms

The transport barrier in intraperitoneal therapy

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