Abstract
Prostate cancer is a leading cause of death in men and despite improved surgical procedures that aid tumor resection, the risk of recurrence after surgery as a result of positive resection margins remains significant. Adjuvant chemotherapy is often required but this is associated with toxicity. Improved ways of delivering highly toxic chemotherapeutic drugs in a more controlled and targeted manner after the prostate has been removed during surgery could reduce the risk of recurrence and avoid systemic toxicity. The aim of this study was to develop a novel drug-device combination tissue scaffold that can be used to deliver the chemotherapeutic agent, docetaxel, into the tissue cavity that is created following radical prostatectomy. The device component investigated consisted of highly porous, poly(dl-lactide-co-glycolide) microparticles made using thermally induced phase separation. A facile method was established for loading docetaxel with high efficiency within one hour. Sustained drug release was observed from the microparticles when placed into a dynamic system simulating tissue perfusion. The drug released from the microparticles into perfusates collected at regular time intervals inhibited colony formation and exhibited sustained cytotoxicity against 3D spheroids of PC3 prostate cancer cells over 10 days. In conclusion, this study demonstrates the concept of combining docetaxel with the biodegradable microparticles at the point of care is technically feasible for achieving an effective drug-device combination tissue scaffold. This approach could provide an effective new approach for delivering adjuvant chemotherapy following radical prostatectomy.
Highlights
Prostate cancer is one of the most prevalent cancers among men and a leading cause of mortality (Taitt, 2018; Miller et al, 2019)
Two cell-based assays using PC3 prostate cancer cells were used to assess whether sustained cytotoxic activity existed for DTX released from thermally induced phase separation (TIPS) microparticles in the perfusate
The colony formation assay revealed DTX released into the perfusate from the TIPS microparticles collected from all time points up to day 10 continued to have an inhibitory effect on the formation PC3 cell colonies (Figure 2(b))
Summary
Prostate cancer is one of the most prevalent cancers among men and a leading cause of mortality (Taitt, 2018; Miller et al, 2019). It is unsurprising that despite being a curative treatment for localized disease, around 50% of patients with high-risk prostate cancer will develop biochemical recurrence following surgery within 5 years and the associated with poor prognosis (Briganti et al, 2015) This outcome is often related to local recurrence either from positive surgical margins or shedding of cancer cells into the peri-prostatic space during extirpative surgery. Even in intermediate risk cases, the incidence of positive surgical margins arising in laparoscopic radical prostatectomy and robotic-assisted radical prostatectomy is reported at $22% (Huang et al, 2017) Many of these patients will require adjuvant or salvage (radiation) therapy or systemic hormonal therapy, which carry higher risks of functional impact on erectile function or urinary continence.
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