Monday, May 19, 2014

PEG-PLA used for delivery of peptide drug for cancer treatment

PolySciTech (www.polyscitech.com) provides a wide array of PEG-PLA copolymers under the polyvivo brand name. Recently this type of copolymer has been utilized to delivery NuBCP-9 anti-cancer peptide to cancer cells triggering apoptosis. Read more: Kumar, Manoj, Dikshi Gupta, Gurpal Singh, Sapna Sharma, Madhusudan Bhatt, C. K. Prashant, A. K. Dinda, Surender Kharbanda, Donald Kufe, and Harpal Singh. "Novel polymeric nanoparticles for intracellular delivery of peptide cargos: antitumor efficacy of the Bcl-2 conversion peptide NuBCP-9." Cancer research (2014): canres-2015. 
http://cancerres.aacrjournals.org/content/early/2014/04/16/0008-5472.CAN-13-2015.short

“Abstract: The preclinical development of peptidyl drugs for cancer treatment is hampered by their poor pharmacological properties and cell penetrative capabilities in vivo. In this study, we report a nanoparticle-based formulation that overcomes these limitations, illustrating their utility in studies of the anti-cancer peptide NuBCP-9 which converts BCL-2 from a cell protector to a cell killer. NuBCP-9 was encapsulated in polymeric nanoparticles (NPs) comprised of a polyethylene glycol (PEG)-modified polylactic acid diblock copolymer (NuBCP-9/PLA-PEG), or PEG-polypropylene glycol-PEG-modified PLA - tetrablock copolymer (NuBCP-9/PLA-PEG-PPG-PEG). We found that peptide encapsulation was enhanced by increasing the PEG chain length in the block copolymers. NuBCP-9 release from the NPs was controlled by both PEG chain length and the PLA molecular weight, permitting time-release over sustained periods. Treatment of human cancer cells with these NPs in vitro triggered apoptosis by NuBCP-9-mediated mechanism, with a potency similar to NuBCP-9 linked to a cell-penetrating poly-Arg peptide. Strikingly, in vivo administration of NuBCP-9/NPs triggered complete regressions in the Ehrlich syngeneic mouse model of solid tumor. Our results illustrate an effective method for sustained delivery of anticancer peptides, highlighting the superior qualities of the novel PLA-PEG-PPG-PEG tetrablock copolymer formulation as a tool to target intracellular proteins.”
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