PLA-PEG-PLA thermogel from PolySciTech used in development of celecoxib delivery system for treatment of breast cancer

 

Breast cancer accounts for 30% of all new cancers in women. There are 670,000 deaths per year due to this disease. Researchers at University of Oklahoma, Medical College of Wisconsin, and Thomas Jefferson University used PLA-PEG-PLA (cat# AK100) from PolySciTech Division of Akina, Inc. (www.polyscitech.com) to develop a thermally responsive hydrogel as a carrier of nanoparticles for delivery of celecoxib. This research holds promise to provide for improved treatment of breast cancer. Read more: Simmons, Reese, Hiroyasu Kameyama, Seiko Kubota, Yunguang Sun, John F. Langenheim, Rana Ajeeb, Tristan S. Shao et al. "Sustained delivery of celecoxib from nanoparticles embedded in hydrogel injected into the biopsy cavity to prevent biopsy-induced breast cancer metastasis." Breast Cancer Research and Treatment (2024): 1-13. https://link.springer.com/article/10.1007/s10549-024-07410-x

“Purpose: We have previously reported that protracted Cyclooxygenase-2 (COX-2) activity in bone marrow-derived cells (BMDCs) infiltrating into biopsy wounds adjacent to the biopsy cavity of breast tumors in mice promotes M2-shift of macrophages and pro-metastatic changes in cancer cells, effects which were suppressed by oral administration of COX-2 inhibitors. Thus, local control of COX-2 activity in the biopsy wound may mitigate biopsy-induced pro-metastatic changes. Methods: A combinatorial delivery system—thermosensitive biodegradable poly(lactic acid) hydrogel (PLA-gel) incorporating celecoxib-encapsulated poly(lactic-co-glycolic acid) nanoparticles (Cx-NP/PLA-gel)—was injected into the biopsy cavity of Py230 murine breast tumors to achieve local control of COX-2 activity in the wound stroma. Results: A single intra-biopsy cavity injection of PLA-gel loaded with rhodamine-encapsulated nanoparticles (NPs) showed sustained local delivery of rhodamine preferentially to infiltrating BMDCs with minimal to no rhodamine uptake by the reticuloendothelial organs in mice. Moreover, significant reductions in M2-like macrophage density, cancer cell epithelial-to-mesenchymal transition, and blood vessel density were observed in response to a single intra-biopsy cavity injection of Cx-NP/PLA-gel compared to PLA-gel loaded with NPs containing no payload. Accordingly, intra-biopsy cavity injection of Cx-NP/PLA-gel led to significantly fewer metastatic cells in the lungs than control-treated mice. Conclusion: This study provides evidence for the feasibility of sustained, local delivery of payload preferential to BMDCs in the wound stroma adjacent to the biopsy cavity using a combinatorial delivery system to reduce localized inflammation and effectively mitigate breast cancer cell dissemination. Keywords: Hydrogel, Nanoparticle, Metastasis, Biopsy, Biopsy site marker, Local drug delivery”

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