Abstract
Depot formulation as a carrier for cytotoxic chemotherapeutic drugs is not well studied. The objective of this study is to test the feasibility of using a subcutaneous depot formulation to administer a cytotoxic anti-cancer drug for systemic therapy. A fatty-acid amide prodrug of the nucleoside analogue gemcitabine (4-(N)-stearoyl gemcitabine (GemC18)) was incorporated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles or microspheres. A GemC18 solution was used as a control. The anti-tumour activity was evaluated after subcutaneous injection of the different formulations in C57BL/6 mice with pre-established model tumours. The clearance of GemC18 from the injection site was determined by measuring the percentage of GemC18 remaining at the injection site at different times after the injection. The depot formulation based on the GemC18-loaded PLGA nanoparticles showed the strongest anti-tumour effect, likely due to the proper 'release' of GemC18 from the injection site. It is feasible to dose cytotoxic anti-cancer drugs as a nanoparticle-based depot formulation, especially when combined with an advanced prodrug strategy.
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