Pegylated Dendrimer and Its Effect in Fluorouracil Loading and Release for Enhancing Antitumor Activity

Abstract

Dendrimer, a new class of hyper-branched polymer with predetermined molecular weight, is being received much attention in nano biomedical applications such as anticancer drug delivery, gene therapy, disease diagnosis and etc. In this study, polyamidoamine (PAMAM)-based dendrimer generation 3.0 (G 3.0) was synthesized and subsequently pegylated. Obtained results showed that pegylation degree of the dendrimer was around 31% for its external amine groups. TEM image of the pegylated dendrimer exhibited spherical shape and nano sizes ranging from 30 to 40 nm. The fluorouracil (5-FU)-loaded pegylated dendrimer showed a slow release profile of the drug. In vitro study, at the primary screening concentration of 100 microg/mL, the PAMAM dendrimer presented higher toxicity in MCF-7 cells as compared to its pegylated counterpart. Meanwhile, the (5-FU)-loaded pegylated dendrimer exhibited the antiproliferative activity against the cell line with the IC50 of 9.92 +/- 0.19 microg/mL. In vivo tumor xenograft study, we succeeded in generating MCF-7 cells-derived cancer tumors on mice that was well-confirmed by using flow cytometer assay. The 5-FU encapsulated pegylated dendrimer exhibited a significant decrement in volume of the tumors which was generated by MCF-7 cancer cells.

Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy

“…Dendrimers have been used as passive anticancer nanocarriers [365,369,370,[377][378][379]. An early example of in vivo passive targeting Is the conjugation of a sodium carboxyl-terminated G-3.5 polyamidoamine (PAMAM) dendrimer with cisplatin for the treatment of B16F10 induced melanomas, achieving an enhanced antitumor efficacy compared with the free drug [372].…”

1H NMR Spectroscopy as an Effective Method for Predicting Molecular Weight of Polyaminoamine Dendrimers and Their Derivatives

“…Many generations and derivatives of PAMAM have been being studied and applied in biomedical fields such as drug=gene delivery nanocarriers and therapeutic=diagnostic nanodevices, among others. [10][11][12][13] Theoretically, generations of PAMAM are synthesized with well-controlled molecular weight by two step-by-step effective reactions, as shown in Scheme 1. [10] However, at high generations, it may be hard for their molecular weights to reach their theoretical values due to steric effect.…”

Dendrimers as Drug Nanocarriers: The Future of Gene Therapy and Targeted Therapies in Cancer

“…Dendrimers have already been used as passive anticancer nanocarriers [38][39][40][41]. There are preclinical promising results in vitro as well as in vivo with active targeting dendrimers [36].…”