Abstract
Dendrimers were well-known as a polymeric nanoparticle drug carrier system. Among them, polyamidoamine (PAMAM) dendrimers were firstly and systematically studied. Herein, to explore the additional modification of PAMAM for drug deliver application, this study assessed the PEGylated half-generation G3.5 to load oxaliplatin (OXA). The proton nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectroscopy (FTIR) spectroscopy were used to confirm the successful synthesis of G3.5, and PEGylated G3.5. PEG modification on G3.5 neutralized the negative charge of G3.5 that was confirmed by zeta potential measurement, and increased the dimension of G3.5 from 10 to 100 nm that was carried out by TEM technique. G3.5-PEG showed the high drug loading efficiency of 75.69%. The release kinetic of OXA from G3.5-PEG@OXA indicated that no burst released phenomenon occurred (11.95% within first hour) and sustainable release was achieved. In cytotoxicity test with normal cells of L929 fibroblasts, the carrier system of G3.5-PEG did not induced any cytotoxicity. To test the killing effect of G3.5-PEG@OXA on cancerous cells of human cervical cancer cells (HeLa), lung adenocarcinoma (A549), and breast cancer (MCF-7), resazurin test and live/dead staining assay was used to observe the alive cells. The increase of OXA amount in G3.5-PEG@OXA lead to decrease the cell viability from 79.90–56.97% (HeLa), 84.80–64.00% (A549), and 92.00–65.00% (MCF-7) after 48 h treatment.
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References
David A (2017) Peptide ligand-modified nanomedicines for targeting cells at the tumor microenvironment. Adv Drug Deliv Rev 119:120–142
Danhier F (2016) To exploit the tumor microenvironment: since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release 244 (Pt A:108–121
Mintzer MA, Grinstaff MW (2011) Biomedical applications of dendrimers: a tutorial. Chem Soc Rev 40(1):173–190
Grabchev I, Staneva D, Vasileva-Tonkova E, Alexandrova R, Cangiotti M, Fattori A, Ottaviani MF (2017) Аntimicrobial and anticancer activity of new poly(propyleneamine) metallodendrimers. J Polym Res 24(11):210
Svenson S, Tomalia DA (2005) Dendrimers in biomedical applications--reflections on the field. Adv Drug Deliv Rev 57(15):2106–2129
D'Souza AA, Shegokar R (2016) Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opin Drug Deliv 13(9):1257–1275
Torchilin VP (1998) Polymer-coated long-circulating microparticulate pharmaceuticals. J Microencapsul 15(1):1–19
Baker DP, Lin EY, Lin K, Pellegrini M, Petter RC, Chen LL, Arduini RM, Brickelmaier M, Wen D, Hess DM, Chen L, Grant D, Whitty A, Gill A, Lindner DJ, Pepinsky RB (2006) N-terminally PEGylated human interferon-beta-1a with improved pharmacokinetic properties and in vivo efficacy in a melanoma angiogenesis model. Bioconjug Chem 17(1):179–188
Alcindor T, Beauger N (2011) Oxaliplatin: a review in the era of molecularly targeted therapy. Curr Oncol 18(1):18–25
Chen Y, Huang Z, Zhao H, Xu JF, Sun Z, Zhang X (2017) Supramolecular chemotherapy: cooperative enhancement of antitumor activity by combining controlled release of Oxaliplatin and consuming of Spermine by cucurbit[7]uril. ACS Appl Mater Interfaces 9(10):8602–8608
Thanh VM, Nguyen TH, Tran TV, Ngoc UP, Ho MN, Nguyen TT, Chau YNT, Le VT, Tran NQ, Nguyen CK, Nguyen DH (2018) Low systemic toxicity nanocarriers fabricated from heparin-mPEG and PAMAM dendrimers for controlled drug release. Mater Sci Eng C Mater Biol Appl 82:291–298
Tummala S, Kumar MN, Pindiprolu SK (2016) Improved anti-tumor activity of oxaliplatin by encapsulating in anti-DR5 targeted gold nanoparticles. Drug Deliv 23(9):3505–3519
Forbes LM, O’Mahony AM, Sattayasamitsathit S, Wang J, Cha JN (2011) Polymer end-group mediated synthesis of well-defined catalytically active platinum nanoparticles. J Mater Chem 21(39):15788
Zhu S, Hong M, Tang G, Qian L, Lin J, Jiang Y, Pei Y (2010) Partly PEGylated polyamidoamine dendrimer for tumor-selective targeting of doxorubicin: the effects of PEGylation degree and drug conjugation style. Biomaterials 31(6):1360–1371
Kaminskas LM, Boyd BJ, Porter CJ (2011) Dendrimer pharmacokinetics: the effect of size, structure and surface characteristics on ADME properties. Nanomedicine 6(6):1063–1084
Yavuz B, Pehlivan SB, Unlu N (2013) Dendrimeric systems and their applications in ocular drug delivery. Sci World J 2013:732340
Osada K, Christie RJ, Kataoka K (2009) Polymeric micelles from poly(ethylene glycol)-poly(amino acid) block copolymer for drug and gene delivery. J Royal Soc Interface 3:S325–S339
Sawant S, Shegokar R (2014) Cancer research and therapy: where are we today? IJCTO 2(4):020408
Yellepeddi VK, Ghandehari H (2016) Poly(amido amine) dendrimers in oral delivery. Tissue Barriers 4(2):e1173773
Chen W, Tomalia DA, Thomas JL (2000) Unusual pH-dependent polarity changes in PAMAM dendrimers: evidence for pH-responsive conformational changes. Macromolecules 33(25):9169–9172
Zhao Z, Lou S, Hu Y, Zhu J, Zhang C (2017) A Nano-in-Nano polymer-dendrimer nanoparticle-based Nanosystem for controlled multidrug delivery. Mol Pharm 14(8):2697–2710
Kang SJ, Durairaj C, Kompella UB, O'Brien JM, Grossniklaus HE (2009) Subconjunctival nanoparticle carboplatin in the treatment of murine retinoblastoma. Arch Ophthalmol 127(8):1043–1047
Patil AS, Gadad AP, Hiremath RD, Joshi SD (2018) Biocompatible tumor micro-environment responsive CS-g-PNIPAAm co-polymeric nanoparticles for targeted Oxaliplatin delivery. J Polym Res 25(3):77
William-Faltaos S, Rouillard D, Lechat P (2007) Cell cycle arrest by oxaliplatin on cancer cells. Fundam Clin Pharmacol 21(2):165–172
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Nguyen, D.T.D., Bach, L.G., Nguyen, T.H. et al. Preparation and characterization of oxaliplatin drug delivery vehicle based on PEGylated half-generation PAMAM dendrimer. J Polym Res 26, 116 (2019). https://doi.org/10.1007/s10965-019-1779-4
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DOI: https://doi.org/10.1007/s10965-019-1779-4