Advancing a surfactant-free sustainable drug delivery system based on the Amazon Astrocaryum murumuru butter for topical application

There is a growing demand for sustainable and biocompatible materials in drug delivery systems, particularly for topical applications. In this context, a lipid-based liquid crystalline (LLC) system, surfactant-free, was developed using Astrocaryum murumuru butter, aiming to provide an effective and environmentally friendly platform for sustained drug release. Two LLC formulations containing metronidazole (MDZ, 100 mg/g) were prepared: one with a surfactant (LLC1) and one surfactant-free (LLC2). Both formulations exhibited a hexagonal mesophase structure, which is known to support sustained drug release. Swelling studies showed similar water uptake, with LLC1 absorbing 29% water within the first hour (reaching 73% at 12 hours) and LLC2 absorbing 36% in 1 hour (42% at 12 hours). Drug release experiments demonstrated sustained release profiles for both formulations, with 68% (LLC1) and 74% (LLC2) of MDZ released over 12 hours, extending up to 48 hours, while a commercial gel released the drug fully within 10 hours. Both LLCs followed first-order release kinetics. Ex vivo skin penetration studies revealed significantly enhanced dermal penetration of MDZ from the surfactant-free LLC2 compared to LLC1. Additionally, in silico toxicity assessment predicted no skin sensitization risk for the surfactant-free formulation, supporting its safety for topical use. Overall, the surfactant-free LLC based on A. murumuru butter represents a safe, biocompatible, effective, and sustainable alternative for topical drug delivery. This platform aims to promote environmentally friendly pharmaceutical and cosmetic formulations that require improved therapeutic performance, emphasizing the potential of Amazonian plant materials in sustainable pharmaceutical technologies. • Surfactant-free LLC uses sustainable A. murumuru butter for topical delivery. • Both LLCs show hexagonal mesophase, enabling sustained metronidazole release. • LLC2 (surfactant-free) enhances skin permeation compared to surfactant LLC1 • In silico analysis indicates LLC2 is non-sensitizing and safer for skin use. • LLC platform offers an eco-friendly alternative for pharmaceutical formulations.