John Garner

PLGA-cholesterol from PolySciTech used in development of bone-targeting nanoparticles as treatment for bone-marrow diseases

Blog Post created by John Garner on Oct 20, 2017

Xiaoyan, 2017 PLGA-cholesterol bone targeting polyscitech.jpg

Delivery of medicinal molecules to bone tissue is very difficult as bone tissue is dense and poorly vascularized. Diseases of bone-marrow are particularly difficult to treat and can lead to death if they progress into leukemia. Recently, researchers working at Houston Methodist Research Institute, Weill Cornell Medical College, Harbin Medical University, and Huazhong University of Science and Technology (China) used cholesterol-endcapped from PolySciTech (www.polyscitech.com) (PolyVivo AP097) to develop a bone-targeting nanoparticle loaded with decitabine and arsenic trioxide, medicines which are effective at treating bone-marrow disorders. This particle was found to have preferential uptake into bone tissue and restored blood counts in a mouse model. This research holds promise for improved treatments for leukemia and other bone-marrow related diseases. Read more: Wu, Xiaoyan, Zhenhua Hu, Sara Nizzero, Guodong Zhang, R. Maricela Ramirez, Ce Shi, Jin Zhou, Mauro Ferrari, and Haifa Shen. "Bone-targeting nanoparticle to co-deliver decitabine and arsenic trioxide for effective therapy of myelodysplastic syndrome with low systemic toxicity." Journal of Controlled Release (2017). http://www.sciencedirect.com/science/article/pii/S016836591730901X

 

“Abstract: Myelodysplastic syndromes (MDS) are a diverse group of bone marrow disorders and clonal hematopoietic stem cell disorders characterized by abnormal blood cells, or reduced peripheral blood cell count. Recent clinical studies on combination therapy of decitabine (DAC) and arsenic trioxide (ATO) have demonstrated synergy on MDS treatment, but the treatment can cause significant side effects to patients. In addition, both drugs have to be administered on a daily basis due to their short half-lives. In addressing key issues of reducing toxic side effects and improving pharmacokinetic profiles of the therapeutic agents, we have developed a new formulation by co-packaging DAC and ATO into alendronate-conjugated bone-targeting nanoparticles (BTNPs). Our pharmacokinetic studies revealed that intravenously administered BTNPs increased circulation time up to 3 days. Biodistribution analysis showed that the BTNP facilitated DAC and ATO accumulation in the bone, which is 6.7 and 7.9 times more than untargeted NP. Finally, MDS mouse model treated with BTNPs showed better restoration of complete blood count to normal level, and significantly longer median survival as compared to free drugs or untargeted NPs treatment. Our results support bone-targeted co-delivery of DAC and ATO for effective treatment of MDS. Keywords: Myelodysplastic syndrome; Bone marrow; Delivery; Nanoparticle; Decitabine; Arsenic trioxide”

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