Biodegradable Polymer Implants for Controlled Erufosine Delivery: In Vitro Release Kinetics and Therapeutic Efficacy in Graffi Myeloid Tumor-Bearing Hamsters

Background: The use of biodegradable polymeric implants for localised drug delivery is a strategy for improving cancer treatment, as it maintains high local drug concentrations while minimising systemic toxicity. Erufosine, a third-generation alkylphosphocholine, is active against a wide range of malignant cells, but its clinical application is limited due to the lack of suitable sustained-release formulations. Methods: Biodegradable polymer blends based on poly(ε-caprolactone) (PCL)/polyethylene glycol (PEG) and poly(D,L-lactide-co-glycolide) (PLGL)/PEG were developed as local drug delivery systems for erufosine. The polymer composition was optimised using doxorubicin as a model compound. Erufosine release was quantified by HPLC–MS/MS over 14 days. The therapeutic efficacy of the implants was evaluated in Graffi myeloid tumor bearing hamsters using two implantation strategies: primary implantation at the time of tumor inoculation and postoperative implantation following tumor resection (using primary and postoperative implantation). Histopathological examination was performed to assess tissue response and tumor morphology. Results: Incorporation of PEG significantly enhanced drug release from the biodegradable matrices, with the PCL/PEG (2:1, w/w) and PLGL/PEG (2:1, w/w) formulations showing the most favourable release profile. HPLC-MS/MS analysis showed an initial burst release followed by sustained erufosine release for up to 14 days. Local implantation of erufosine-loaded carriers significantly prolonged survival and decreased mortality of Graffi tumour-bearing hamsters with postoperatively drug-loaded implants. Histopathological analysis revealed extensive tumor cell degeneration and necrosis, confirming the biological activity of locally released erufosine. In PLGL/PEG-treated animals, the formation of a fibrovascular capsule around the implant suggested that host tissue response might partially restrict drug diffusion despite favourable in vitro release kinetics. Conclusions: Biodegradable PCL/PEG and PLGL/PEG implants provide sustained local erufosine delivery and moderate antitumor activity in vivo. The findings demonstrate that therapeutic efficacy depends not only on polymer-controlled drug release but also on the response of host tissues to the implanted biomaterial