Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

Tóm tắt

Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50–100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

Từ khoá

PLA-TPGS nanoparticles, targeted delivery, folate, cancer

Tài liệu tham khảo

[1] Gu F X, Karnik R, Wang A Z, Alexis F, Levy-Nissenbaum E, Hong S, Langer R S and Farokhzad O C 2007 Nano Today 2 14
[2] Maeda H 2001 Adv. Enzyme Regul. 41 189
[3] Moghimi S M, Hunter A C and Murray J C 2001 Pharmacol. Rev. 53 283
[4] Byrne J D, Betancourt T and Brannon-Peppas L 2008 Adv. Drug Deliv. Rev. 60 1615
[5] Xiao R Z, Zeng Z W, Zhou G L, Wang J J, Li F Z and Wang A M 2010 Int. J. Nanomedicine 5 1057
[6] Lee S H, Zhang Z and Feng S-S 2007 Biomaterials 28 2041
[7] Miyata K, Christie R J and Kataoka K 2011 React. Funct. Polym. 71 227
[8] Xu W, Ling P and Zhang T 2013 J. Drug Delivery 2013 15
[9] Ha P T, Tran T M N, Pham H D, Nguyen Q H and Nguyen X P 2010 Adv. Nat. Sci.: Nanosci. Nanotechnol. 1 015012
[10] Pan J and Feng S-S 2008 Biomater. 29 2663
[11] Nguyen H N, Thi H H T, Quang D L, Thi T N, Thi N H T, Le M H and Ha P T 2012 Adv. Nat. Sci.: Nanosci. Nanotechnol. 3 045005
[12] Thu H P, Nam N H, Quang B T, Son H A, Toan N L and Quang D T 2015 Saudi Pharmaceutical Journal 23 683
[13] Devi T R and Gayathri S 2010 Int. J. Pharm. Sci. Rev. Research 2 106
[14] Zhang J, Rana S, Srivastava R S and Misra R D K 2008 Acta Biomater. 4 40
[15] Nguyen H N, Hoang T M N, Mai T T T, Nguyen T Q T, Do H D, Pham T H, Nguyen T L and Ha P T 2015 Adv. Nat. Sci.: Nanosci. Nanotechnol. 6 025005
[16] Sahay G, Alakhova D Y and Kabanov A V 2010 J. Control. Release 145 182
[17] Dalmark M and Storm H H 1981 J. Gen. Physiol. 78 349