Novel Self-Nanoemulsifying Drug-Delivery System Enhances Antileukemic Properties of All- Trans Retinoic Acid

Abstract

<jats:p> 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. </jats:p>

Nanoemulsified Essential Oil of Melaleuca leucadendron Leaves for Topical Application: In Vitro Photoprotective, Antioxidant and Anti-Melanoma Activities

“…Transmission electron microscopy (TEM) is an effective characterization technique that can provide data on the morphology and particle size of nanostructured systems [ 37 , 38 ].…”

Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide

“…It has been shown that ATRA could sensitize the myocardium to the toxic effects of anthracyclines [42]. Moreover, SNEDDS-TRF-ATRA may promote higher ATRA plasma concentrations than an ATRA-solution after oral administration [20]. Thus, the observed mortality may be related to the possible cardiotoxic impact caused by the combination of ATO plus ATRA and the administration of SNEDDSTRF-ATRA does not seem to diminish the toxicity caused by ATO in this context.…”

“…The SNEDDS-TRFATRA, after dilution in a simulated gastric fluid, presented a mean average size of 66 ± 8 nm, a PDI value of 0.09 ± 0.00, and an ATRA encapsulation efficiency of 89.6 ± 9.3%. The SNEDDS-TRF-ATRA, after dilution in a simulated intestinal fluid, presented a mean average size of 64 ± 1 nm, a PDI value of 0.12 ± 0.05, and an ATRA encapsulation efficiency of 89.1 ± 4.2% [20].…”

“…We prepared SNEDDS-TRF-ATRA as described by Marques Borges et al [20]. Briefly: soybean oil (37.5%), TRF (15%), Cremophor® RH40 (15%), Tween™ 80 (15%), Span™ 80 (10%), and PEG 400 (5%) were weighed into an amber penicillin vial and allowed to stir for 30 min at 50°C.…”

“…We have previously shown that a tocotrienol-enriched self-nanoemulsifying drug delivery system (SNEDDS) designed to deliver ATRA (SNEDDS-TRF-ATRA) could enhance oral ATRA bioavailability and its cytotoxicity in HL-60 (human APL) cells. The presence of tocotrienol in the SNEDDS was due to the presence of a tocotrienol-rich fraction (TRF) derived from palm oil [20]. Herein, we evaluated the cytotoxicity and differentiating properties of SNEDDS-TRF-ATRA in sensitive (NB4) and resistant (NB4-R2) APL cell lines.…”