John Garner

mPEG-PLLA from PolySciTech used in development of phosphovalproic acid based pancreatic cancer treatment

Blog Post created by John Garner on Sep 1, 2017

Mattheolabakis, 2017 PolySciTech PEG-PLLA phosphovalproic acid.png

The word “cancer” actually describes a broad range of diseases that can affect many different parts of the body. Some cancers, such as skin cancer, respond well to treatment by conventional therapies and have a good prognosis. Other cancers, notably pancreatic, are very difficult to treat and often prove fatal. Recently, researchers working at Stony Brook University, University of Louisiana, and University of California utilized PEG-PLLA (Polyvivo AK004) from PolySciTech (www.polyscitech.com) as part of developing a nanoparticle-based phosphovalproic acid delivery system for treating pancreatic cancer. The developed system showed promise in an animal model for preventing the growth of pancreatic cancer. This research holds promise for a treatment to this lethal disease. Read more: Mattheolabakis, George, Ruixue Wang, Basil Rigas, and Gerardo G. Mackenzie. "Phospho-valproic acid inhibits pancreatic cancer growth in mice: enhanced efficacy by its formulation in poly-(L)-lactic acid-poly (ethylene glycol) nanoparticles." International Journal of Oncology. https://www.spandidos-publications.com/10.3892/ijo.2017.4103/download

 

  “Pancreatic cancer (PC) is one of the most difficult cancers to treat. Since the current chemotherapy is inadequate and various biological approaches have failed, the need for agents that have a potential to treat PC is pressing. Phospho-valproic acid (P-V), a novel anticancer agent, is efficacious in xenograft models of human PC and is apparently safe. In the present study, we evaluated whether formulating P-V in nanoparticles could enhance its anticancer efficacy. In a mouse model of Kras/pancreatitis-associated PC, P-V, orally administered, inhibited the incidence of acinar-to-ductal metaplasia by 60%. To improve its efficacy, we formulated P-V in five different polymeric nanoparticles. Poly-(L)-lactic acid- poly(ethylene glycol) (PLLA-PEG) nanoparticles proved the optimal formulation. PLLA-PEG improved P-V's pharmacokinetics in mice enhancing the levels of P-V in blood. Compared to control, P-V formulated in PLLA-PEG suppressed the growth of MIA PaCa-2 xenografts by 81%, whereas P-V alone reduced it by 51% (p<0.01). Furthermore, P-V formulated in PLLA-PEG inhibited acinar-to-ductal metaplasia in mice with activated Kras, reducing it by 87% (p<0.02). In both disease models, P-V suppressed STAT3 phosphorylation at the Ser727 and Tyr705 residues; STAT3 is the pivotal molecular target of P-V. In conclusion, P-V is a promising agent against PC, and its formulation in PLLA-PEG nanoparticles enhances its efficacy by improving its pharmacokinetics.”

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