Abstract
Recurrence of prostate cancer after radical prostatectomy is a consequence of incomplete tumor resection. Systemic chemotherapy after surgery is associated with significant toxicity. Improved delivery methods for toxic drugs capable of targeting positive resection margins can reduce tumor recurrence and avoid their known toxicity. This study evaluates the effectiveness and toxicity of docetaxel (DTX) release from highly porous biodegradable microparticles intended for delivery into the tissue cavity created during radical prostatectomy to target residual tumor cells. The microparticles, composed of poly(dl‐lactide‐co‐glycolide) (PLGA), are processed using thermally induced phase separation (TIPS) and loaded with DTX via antisolvent precipitation. Sustained drug release and effective toxicity in vitro are observed against PC3 human prostate cells. Peritumoral injection in a PC3 xenograft tumor model results in tumor growth inhibition equivalent to that achieved with intravenous delivery of DTX. Unlike intravenous delivery of DTX, implantation of DTX‐TIPS microparticles is not accompanied by toxicity or elevated systemic levels of DTX in organ tissues or plasma. DTX‐TIPS microparticles provide localized and sustained release of nontoxic therapeutic amounts of DTX. This may offer novel therapeutic strategies for improving management of patients with clinically localized high‐risk disease requiring radical prostatectomy and other solid cancers at high risk of positive resection margins.
Highlights
Recent years have seen many patients benefitting from the availability of new of incomplete tumor resection
The amount of DTX loaded onto the thermally induced phase separation (TIPS) microparticles was indirectly quantified by measuring the amount of DTX remaining in solution at different time points during the loading phase
Scanning electron microscopy of the microparticles confirmed the presence of crystalline DTX on the surface of the microparticles following incubation in the DTX solution, which was absent in unloaded control TIPS microparticles (Figure 1)
Summary
The amount of DTX loaded onto the TIPS microparticles was indirectly quantified by measuring the amount of DTX remaining in solution at different time points during the loading phase. Scanning electron microscopy of the microparticles confirmed the presence of crystalline DTX on the surface of the microparticles following incubation in the DTX solution, which was absent in unloaded control TIPS microparticles (Figure 1)
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