scholarly journals All-Trans Retinoic Acid Grafted Poly Beta-Amino Ester Nanoparticles: A Novel Anti-angiogenic Drug Delivery System

2020 ◽  
Vol 10 (2) ◽  
pp. 221-232 ◽  
Author(s):  
Nadia Karimi ◽  
Kamaran Mansouri ◽  
Mohammad Soleiman-Beigi ◽  
Ali Fattahi

Purpose: Developing chemotherapy with nanoplatforms offers a promising strategy for effective cancer treatment. In the present study, we propose a novel all-trans retinoic acid (ATRA) grafted poly beta-amino ester (PBAE) copolymer for preparing nanoparticles (NPs). Methods: ATRA grafted PBAE (ATRA-g-PBAE) copolymer was synthesized by grafting ATRA to PBAE; it was characterized by proton nuclear magnetic resonance, Fourier transform infrared, and thermogravimetric analysis. ATRA-g-PBAE NPs were prepared by the solvent displacement method. Design-Expert software was employed to optimize size of NPs. The morphology was evaluated by transmission electron microscope, and ultraviolet-visible spectroscopy was applied for drug release. Cytotoxicity was evaluated toward HUVEC cell line, and the 3D collagencytodex model was used to evaluate anti-angiogenic property of PBAE, ATRA, and NPs. Results: The optimum size of the NPs was 139.4 ± 1.41 nm. After 21 days, 66.09% ± 1.39 and 42.14% ± 1.07 of ATRA were released from NPs at pH 5.8 and 7.4, respectively. Cell culture studies demonstrated antiangiogenic effects of ATRA-g-PBAE NPs. Anti-angiogenesis IC50 was 0.007 mg/mL for NPs (equal to 0.002 mg/mL of ATRA) and 0.005 mg/mL for free ATRA. Conclusion: This study proposes the ATRA-g-PBAE NPs with inherent anti-angiogenic effects as promising carrier for anticancer drugs with purpose of dual drug delivery.

2004 ◽  
Vol 279 (44) ◽  
pp. 45708-45712 ◽  
Author(s):  
Kristin M. Nieman ◽  
Matthew J. Rowling ◽  
Timothy A. Garrow ◽  
Kevin L. Schalinske

The hepatic enzyme glycineN-methyltransferase (GNMT) plays a major role in the control of methyl group and homocysteine metabolism. Because disruption of these vital pathways is associated with numerous pathologies, understanding GNMT control is important for evaluating methyl group regulation. Recently, gluconeogenic conditions have been shown to modulate homocysteine metabolism and treatment with glucocorticoids and/or all-trans-retinoic acid (RA)-induced active GNMT protein, thereby leading to methyl group loss. This study was conducted to determine the effect of diabetes, alone and in combination with RA, on GNMT regulation. Diabetes and RA increased GNMT activity 87 and 148%, respectively. Moreover, the induction of GNMT activity by diabetes and RA was reflected in its abundance. Cell culture studies demonstrated that pretreatment with insulin prevented GNMT induction by both RA and dexamethasone. There was a significant decline in homocysteine concentrations in diabetic rats, owing in part to a 38% increase in the abundance of the transsulfuration enzyme cystathionine β-synthase; treatment of diabetic rats with RA prevented cystathionine β-synthase induction. A diabetic state also increased the activity of the folate-independent homocysteine remethylation enzyme betaine-homocysteineS-methyltransferase, whereas the activity of the folate-dependent enzyme methionine synthase was diminished 52%. In contrast, RA treatment attenuated the streptozotocin-mediated increase in betaine-homocysteineS-methyltransferase, whereas methionine synthase activity remained diminished. These results indicate that both a diabetic condition and RA treatment have marked effects on the metabolism of methyl groups and homocysteine, a finding that may have significant implications for diabetics and their potential sensitivity to retinoids.


2013 ◽  
Vol 19 (2) ◽  
pp. 164-172 ◽  
Author(s):  
Ponwanit Charoenputtakhun ◽  
Praneet Opanasopit ◽  
Theerasak Rojanarata ◽  
Tanasait Ngawhirunpat

Nanomedicine ◽  
2020 ◽  
Vol 15 (15) ◽  
pp. 1471-1486
Author(s):  
Gabriel Silva Marques Borges ◽  
Micael de Oliveira Ferencs ◽  
Cristina de Mello Gomide Loures ◽  
Mostafa AL Abdel-Salam ◽  
Fernanda Cristina Gontijo Evangelista ◽  
...  

Aim: All- trans retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. Results: SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion. Pharmacokinetic parameters after oral administration of SEDDS-TRF-ATRA-BZT in mice were improved compared with what was seen for an ATRA solution. Moreover, SEDDS-TRF-ATRA-BZT had improved activity against HL-60 cells compared with SEDDS without TRF. Conclusion: SEDDS-TRF-ATRA-BZT is a promising therapeutic choice over ATRA conventional medicine.


2017 ◽  
Author(s):  
A Prawan ◽  
S Butsri ◽  
V Kukongviriyapan ◽  
L Senggunprai ◽  
S Kongpetch

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