Abstract
Tamoxifen represents the endocrine treatment of choice for hormone-dependent breast cancer. However, undesirable side effects appeared after long-term therapy. Therefore, the concept of a drug delivery system at the tumour site is an interesting alternative. The aim of this work was to evaluate the potential of an original in situ forming gel to allow sustained delivery of tamoxifen. The gel forms spontaneously when two aqueous polymeric solutions are put in contact: a cyclodextrin (CD) polymer and dextran grafted with alkyl side chains. Some hydrophobic chains form inclusion complexes with CDs, leaving also free CDs available for the inclusion of drug molecules. Phase solubility studies showed a dramatically increased apparent solubility of tamoxifen in water (80-fold) in the presence of the CD polymer. Moreover, this drug was successfully entrapped in the gels, with loading efficiencies around 90%. Tamoxifen was released following a zero-order release profile during four days, followed by gel dissolution. The estimated amount of gel to be formed in situ to achieve in vivo anti-proliferative effects was found to be compatible with an injection. Moreover, this new concept opens a large domain of perspectives for other types of pathologies, where soft matrices allowing local drug sustained release are required.
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