PLGA from PolySciTech used in comparative assay of nanoparticle delivery and drug release

The pathway to generating drug-delivery technologies to treat cancer is not necessarily linear as the process is complex. Notably, the motion of the nanoparticles does not always correlate to successful delivery of drug to the tumor. Recently, researchers at Seoul National University, Catholic University of Korea (Korea), and Purdue University used PLGA (AP020) from PolySciTech (www.polyscitech.com) to create quinic-acid decorated nanoparticles. They found that the motion of the particles did not correlate to efficacy, however, indicating that the release of carfizomib is the limiting step for efficacy. Read more: Jun, Yearin, Jun Xu, Hyungjun Kim, Ji Eun Park, Yoo-Seong Jeong, Jee Sun Min, Naeun Yoon et al. "Carfilzomib delivery by quinic acid-conjugated nanoparticles: Discrepancy between tumoral drug accumulation and anticancer efficacy in a murine 4T1 orthotopic breast cancer model." Journal of Pharmaceutical Sciences (2020). https://www.sciencedirect.com/science/article/pii/S0022354920300137

“Abstract: Despite being a major breakthrough in multiple myeloma therapy, carfilzomib (CFZ, a second-generation proteasome inhibitor drug) has been largely ineffective against solid cancer, possibly due to its pharmacokinetic drawbacks including metabolic instability. Recently, quinic acid (QA, a low-affinity ligand of selectins upregulated in peritumoral vasculature) was successfully utilized as a surface modifier for nanoparticles containing paclitaxel. Here, we designed QA-conjugated nanoparticles containing CFZ (CFZ@QANP; the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles modified by conjugation with a QA derivative). Compared to the clinically used cyclodextrin-based formulation (CFZ-CD), CFZ@QANP enhanced the metabolic stability and in vivo exposure of CFZ in mice. CFZ@QANP however showed little improvement in suppressing tumor growth over CFZ-CD against the murine 4T1 orthotopic breast cancer model. CFZ@QANP yielded no enhancement in proteasomal inhibition in excised tumors despite having a higher level of remaining CFZ than CFZ-CD. These results likely arise from delayed, incomplete CFZ release from CFZ@QANP as observed using biorelevant media in vitro. These results suggest that the applicability of QANP may not be predicted by physicochemical parameters commonly used for formulation design. Our current results highlight the importance of considering drug release kinetics in designing effective CFZ formulations for solid cancer therapy. Keywords: Proteasome inhibitor carfilzomib nanoparticle quinic acid”

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