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

Geraldine Sandana Mala John,Ravi Shankar Pitani,Satoru Takeuchi,Veena Kumari Vuttaradhi,Suresh Kumar Rayala,Ganesh Venkatraman

doi:10.1186/s12951-020-00628-z

Abstract

BackgroundNordihydroguaiaretic 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.ResultsThe 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.ConclusionsThe present studies indicate a new and efficient formulation of the nanostructured AcNDGA with good therapeutic potential.

Highlights

Nordihydroguaiaretic acid (NDGA) is obtained from creosote bush, Larrea tridentata, commonly found in desert regions of North America and Mexico
Synthesis of tetra‐O‐acetyl nordihydroguaiaretic acid derivative Acetyl NDGA was synthesized by a chemical procedure as previously described by Plaza et al [27] with some conditions adapted in our laboratory
PCL has been used in several biomedical applications in drug delivery, tissue engineering, in implants and devices owing to its biodegradability, biocompatibility, low immunogenicity and little or no antigenicity [30]

Summary

Introduction

Nordihydroguaiaretic acid (NDGA) is obtained from creosote bush, Larrea tridentata, commonly found in desert regions of North America and Mexico. During the past two decades, chemical synthesis of NDGA analogs have been carried out by several researchers demonstrating the newly acquired properties/therapeutic effects of the derivatized NDGA with different chemical moieties [10,11,12]. This has been a promising approach to reduce/eliminate the toxicity implications of the native drug, but there is a need for further investigations of the reduction of toxicity of NDGA analogs in vivo by supported literature. NDGA derivatives have been developed as better alternatives to NDGA and for targeted delivery to the site of tissue by chemical derivatives. 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

Methods

Results

Conclusion