| Autor: |
Azab AK; Department of Pharmaceutics, The Hebrew University of Jerusalem, School of Pharmacy, Jerusalem, Israel., Kleinstern J, Doviner V, Orkin B, Srebnik M, Nissan A, Rubinstein A |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2007 Nov 06; Vol. 123 (2), pp. 116-22. Date of Electronic Publication: 2007 Aug 08. |
| DOI: |
10.1016/j.jconrel.2007.07.014 |
| Abstrakt: |
Brachytherapy has many potential roles in cancer therapy. However, major constraints are associated with placement and removal procedures of the brachytherapy machinery. An attractive approach would be the use of a biodegradable implant loaded with a radioisotope, thus enabling targeted radiotherapy, while reducing the need for surgical procedures for the removal of brachytherapy hardware. In this study, crosslinked chitosan (Ct) hydrogels were prepared and loaded with (131)I-norcholesterol ((131)I-NC). The radioactive hydrogels ((131)I-NC-Ct) were implanted adjacent to 4T1 cell-induced tumors in two different xenograft mice models either as primary therapy or surgical adjuvant therapy of breast cancer. Non-treated mice and mice implanted with naive (non-radioactive) hydrogels served as control groups. In the primary therapy model, the progression rate of the tumor was delayed by two weeks compared with the non-treated and the naive-implant control animals, resulting in a one-week extension in the survival of the treated animals. In the adjuvant therapy model, for the treatment of minimal residual disease, (131)I-NC-Ct implants were able to prevent 69% of tumor recurrence, and to prevent metastatic spread resulting in long-term survival, compared with 0% long-term survival of the non-treated and the naive control groups. Imaging of the hydrogel's in vivo elimination revealed a first order process with a half-life of 14 days. The degradation was caused by oxidation of the Ct as was assessed by in vitro H&E stain. Biodegradable radioactive implants are suggested as a novel platform for the delivery of brachytherapy. This radiotherapy regimen may prevent locoregional recurrence and metastatic spread after tumor resection. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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