Hyaluronidase induces a transcapillary pressure gradient and improves the distribution and uptake of liposomal doxorubicin (Caelyx™) in human osteosarcoma xenografts
2005

Hyaluronidase Improves Doxorubicin Delivery in Osteosarcoma

Sample size: 6 publication Evidence: moderate

Author Information

Author(s): Eikenes L, Tari M, Tufto I, Bruland ØS, de Lange Davies C

Primary Institution: The Norwegian University of Science and Technology

Hypothesis

Hyaluronidase might induce a transcapillary pressure gradient, thereby improving the tumour uptake and distribution of liposomal doxorubicin within the tumour.

Conclusion

Hyaluronidase reduces a major barrier for drug delivery by inducing a transcapillary pressure gradient, which improves the therapeutic outcome of liposomal doxorubicin.

Supporting Evidence

  • 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.
  • Hyaluronidase induced a transcapillary pressure gradient, resulting in a four-fold increase in the tumour uptake of liposomal doxorubicin.
  • Statistical analysis showed that the maximum reduction in interstitial fluid pressure was significantly lower than control tumours injected with PBS.

Takeaway

Hyaluronidase helps medicine get into tumors better by making it easier for the medicine to move around inside the tumor.

Methodology

The study measured interstitial fluid pressure and microvascular pressure in human osteosarcoma xenografts after administering hyaluronidase and analyzed the distribution of liposomal doxorubicin using confocal laser scanning microscopy.

Limitations

The study was conducted in animal models, which may not fully replicate human responses.

Participant Demographics

7–9-week-old athymic female BALB/c nu/nu mice

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/sj.bjc.6602626

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