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Intravital Microscopy of Tumor-associated Vasculature Using Advanced Dorsal Skinfold Window Chambers on Transgenic Fluorescent Mice
Published on: January 19, 2018
Effects of freezing on intratumoral drug transport
1University of Texas at Arlington, Arlington, TX 76019, USA. bhan@uta.edu
Abstract:
Efficacy of many novel therapeutic agents are impaired by hindered interstitial diffusion in tumor. In the context of overcoming this drug delivery barrier, a hypothesis was postulated that freeze/thaw (F/T) may induce favorable changes of tumor tissue microstructure to facilitate the interstitial diffusion. This hypothesis may also be relevant to develop a mechanistically derived chemotherapeutic strategy for cryo-treated tumors. In the present study, this hypothesis was tested by characterizing the effects of F/T on the interstitial diffusion using an in vitro engineered tumor model (ET). The diffusion coefficients of FITC-labeled dextran was measured within the frozen/thawed and unfrozen ETs. The results showed that the diffusion coefficients increased after F/T but the extent of increase was dependent on the size of dextran. This implies that the combination of cryosurgery and chemotherapy should be designed considering the biophysical changes of tissues after freeze/thaw and the diffusion characteristics of drug molecules.
Insights
Freeze/thaw cycles can improve drug delivery in tumors by altering tissue microstructure, enhancing interstitial diffusion. This finding is crucial for optimizing chemotherapy strategies in cryo-treated cancers.
Area of Science:
- Biomedical Engineering
- Cancer Therapy
- Drug Delivery
Background:
- Tumor interstitial diffusion is a major barrier for novel therapeutic agents.
- Freeze/thaw (F/T) processes are hypothesized to alter tumor microstructure favorably for drug delivery.
Purpose of the Study:
- To test the hypothesis that F/T enhances interstitial diffusion in tumors.
- To investigate F/T effects on tumor tissue microstructure for improved drug delivery.
- To inform the development of chemotherapeutic strategies for cryo-treated tumors.
Main Methods:
- Utilized an in vitro engineered tumor model (ET).
- Characterized the effects of F/T on interstitial diffusion.
- Measured diffusion coefficients of FITC-labeled dextran in frozen/thawed and unfrozen ETs.
Main Results:
- Diffusion coefficients of FITC-labeled dextran increased significantly after F/T.
- The extent of diffusion enhancement was dependent on dextran size.
- F/T induces favorable microstructural changes that facilitate interstitial diffusion.
Conclusions:
- F/T can enhance interstitial diffusion, overcoming a key drug delivery barrier in tumors.
- Combining cryosurgery and chemotherapy requires consideration of F/T-induced biophysical tissue changes.
- Drug molecule diffusion characteristics must be matched with F/T effects for effective cancer treatment.
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