Facile synthesis and nanoscale features of a nanostructured nordihydroguaiaretic acid analog for therapeutic applications

Abstract

Background: Nordihydroguaiaretic acid (NDGA) is a plant lignan obtained from creosote bush, known to possess anti-oxidant, anti-cancer and anti-viral activities and is being used in traditional medicine. However, toxicity studies indicated liver and kidney damage despite its immense medicinal properties. There has been a recent increase of curiosity in the chemical synthesis of NDGA derivatives for therapeutic applications. NDGA derivatives have been developed as better alternatives to NDGA and for targeted delivery to the site of tissue by chemical derivatives. In this regard, an analog of NDGA, Acetyl NDGA (Ac-NDGA), has been synthesized based on a previous procedure and formulated as a nanostructured complex with Polycaprolactone/Polyethylene glycol polymer matrices, by o/w solvent evaporation method. Results: The drug-incorporated polymeric nanospheres exhibited a drug load of 10.0 ± 0.5 µg drug per mg of nanospheres in acetonitrile solvent with 49.95 ± 10% encapsulation efficiency and 33-41% drug loading capacity with different batches of nanospheres preparation. The in vitro drug release characteristics indicated 82 ± 0.25% drug release at 6 h in methanol. Further, the nanospheres have been characterized extensively to evaluate their suitability for therapeutic delivery. Conclusions: The present studies indicate a new and efficient formulation of the nanostructured AcNDGA with good therapeutic potential.

Polymer indicator displacement assay: electrochemical glucose monitoring based on boronic acid receptors and graphene foam competitively binding with poly-nordihydroguaiaretic acid

“…A competitive assay would require a redox active molecule to bind to the boronic acid in competition with glucose, but this would not be practical due to loss of the redox indicator into the solution. However, the introduction of a redox-active polymer (here based on poly-nordihydroguaiaretic acida polymeric material of medicinal interest 13,14 with additional dispersion interaction to the graphene foam substrate) into the boronic acidbased electrochemical sensor design confers many advantages to the sensor. Firstly, the polymer can act as a molecular sieve, filtering out larger molecules in the blood that may disrupt or interfere with glucose sensing (such as plasma proteins and/or red blood cells).…”

Assessing Nordihydroguaiaretic Acid Therapeutic Effect for Glioblastoma Multiforme

“…The Latin name of the plant is Larrea tridentata . Due to its widespread use for alleviating a variety of illnesses, which includes cancer, the plant has been extensively studied [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. The extraction, synthesis, and purification of the plant’s most beneficial active ingredient, the NDGA [ 26 , 27 ], has opened new research opportunities, with abundant literature dedicated to scientifically ascertaining and clarifying the compound’s potential value and underlying mechanisms of action.…”

“…The extraction, synthesis, and purification of the plant’s most beneficial active ingredient, the NDGA [ 26 , 27 ], has opened new research opportunities, with abundant literature dedicated to scientifically ascertaining and clarifying the compound’s potential value and underlying mechanisms of action. Examples consist of preventing kidney stone formation, diabetes, renal infections, neurological disorders, viral infections, and a variety of cancer types [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. It has been established that the NDGA’s antioxidant, anti-viral, and anti-tumorigenic properties are due to the fact that it is a reactive oxygen species (ROS) scavenger, leading to a decrease in inflammation and to the inhibition of several metabolic enzymes and receptor tyrosine kinases [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ].…”

“…Examples consist of preventing kidney stone formation, diabetes, renal infections, neurological disorders, viral infections, and a variety of cancer types [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. It has been established that the NDGA’s antioxidant, anti-viral, and anti-tumorigenic properties are due to the fact that it is a reactive oxygen species (ROS) scavenger, leading to a decrease in inflammation and to the inhibition of several metabolic enzymes and receptor tyrosine kinases [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. It has also been reported that excessive consumption of the plant or administration of the compound at high concentrations can be detrimental and toxic, causing liver damage and kidney dysfunction [ 29 ].…”

“…It has been established that the NDGA’s antioxidant, anti-viral, and anti-tumorigenic properties are due to the fact that it is a reactive oxygen species (ROS) scavenger, leading to a decrease in inflammation and to the inhibition of several metabolic enzymes and receptor tyrosine kinases [ 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 ]. It has also been reported that excessive consumption of the plant or administration of the compound at high concentrations can be detrimental and toxic, causing liver damage and kidney dysfunction [ 29 ]. The cytotoxic effects of NDGA have been attributed to the molecule’s auto-oxidation and its structural transformation into semi-quinone or ortho-quinone forms (the NDGA molecule contains two catechol rings, which are prone to oxidation) [ 30 , 40 ].…”