Role of generation on folic acid-modified poly(amidoamine) dendrimers for targeted delivery of baicalin to cancer cells.

Abstract

Baicalin (BAI) has been reported to exert antitumor effects. However, BAI has limited water solubility, non-specific tumor targeting, and low bioavailability, which severely limited its clinical application. The aim of this study was to develop folic acid (FA) covalently conjugated-polyamidoamine (PAMAM) dendrimers (PAMAM-FA) as carrier systems for improvement of water solubility and tumor-specificity of BAI, and study the role of generation on the physiochemical properties and biological effects of PAMAM-FA/BAI complexes. In this work, four generations of PAMAM-FA were synthesized to entrap BAI. The average sizes of G3-FA/BAI, G4-FA/BAI, G5-FA/BAI, and G6-FA/BAI complexes were 174.4nm, 184.5nm, 258.8nm, and 247.5nm, respectively, and the zeta potentials of four PAMAM-FA/BAI complexes were -2.9mV, -6.6mV, -9.3mV, -9.0mV, respectively. The entrapment efficiencies of four PAMAM-FA/BAI complexes were 91.1%, 53.5%, 80.3%, and 91.9%, respectively, and the drug loading of PAMAM-FA/BAI complexes were about 22%. The formed PAMAM-FA/BAI complexes allowed sustained release of BAI in acidic PBS (pH5.4). In cellular uptake assay, PAMAM-FA/BAI complexes demonstrated increased drug uptake level in folate receptor (FR)-positive Hela cancer cells than FR-negative A549 cells, and the cellular uptake efficiency of PAMAM-FA is closely related with the generation of PAMAM. The MTT assay results showed that PAMAM-FA/BAI complexes demonstrated enhanced toxicity against Hela cells than non-FA-modified PAMAM/BAI complexes, and the G6-FA/BAI demonstrated the best inhibition efficiency. The cell cycle and cell apoptosis analysis further demonstrated the tumor-specific therapeutic efficacy of PAMAM-FA/BAI. These results suggested that the PAMAM-FA have the potential for targeted delivery of BAI into cancer cells to enhance its anti-tumor efficacy.

• Authors: Tingting Lv, Tingting Yu, Yunpeng Fang, Suyan Zhang, Minghong Jiang, Huijuan Zhang, Yingying Zhang, Ziying Li, Haijun Chen, Yu Gao
• Journal: Materials science & engineering. C, Materials for biological applications (Mater Sci Eng C Mater Biol Appl) Vol. 75 Pg. 182-190 (Jun 01 2017) ISSN: 1873-0191 [Electronic] Netherlands
• PMID: 28415453 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Dendrimers
• Flavonoids
• Poly(amidoamine)
• Polyamines
• baicalin
• Folic Acid

Topics

• A549 Cells
• Dendrimers (chemistry, pharmacokinetics, pharmacology)
• Drug Delivery Systems (methods)
• Flavonoids (chemistry, pharmacokinetics, pharmacology)
• Folic Acid (chemistry, pharmacokinetics, pharmacology)
• HeLa Cells
• Humans
• Neoplasms (drug therapy, metabolism, pathology)
• Polyamines (chemistry, pharmacokinetics, pharmacology)