Nanoemulgels as next-generation hybrid platforms for delivering natural bioactive compounds: advances and biomedical applications

Abstract

Nanoemulgels have emerged as advanced drug delivery systems designed to enhance the solubility, bioavailability, and therapeutic efficacy of lipophilic compounds, particularly for the delivery of natural bioactive compounds, including secondary metabolites from plants and microorganisms. By integrating the advantages of both nanoemulsions and hydrogels, these hybrid systems facilitate improved drug delivery and enhanced therapeutic effectiveness. Nanoemulgel-based formulations have demonstrated considerable potential for poorly soluble natural bioactive compounds such as thymoquinone, curcumin, Capsicum annuum oleoresin, and Piper betle essential oil, utilizing surfactant systems including Tween 80 and Span 80, along with gel matrices such as Carbopol®940, Aloe vera gel, and methylcellulose. These formulations result in increased stability, skin permeation, and controlled drug release. The primary limitations of conventional dosage forms arise from the dual hydrophilic and lipophilic properties of the drug, as well as its thermolabile nature, which collectively hinder its therapeutic efficacy in systemic and topical applications. By integrating the stability and controlled-release features of hydrogels with the enhanced solubilization and penetration capabilities of nanoemulsions, nanoemulgels enable precise and sustained delivery of bioactive compounds, concurrently reducing degradation and adverse effects. This sophisticated and uniquely integrated carrier system offers promising solutions for targeted therapies, including wound healing, antimicrobial treatment, inflammatory disorders, and exhibits significant potential in oncological applications. Despite their therapeutic promise, nanoemulgels face notable challenges, including limited scalability, rigorous regulatory approval processes, variability in formulation consistency, and concerns about cytotoxicity at higher doses. Furthermore, the complex relationship between formulation parameters-such as particle size, surface charge, and rheological properties-and biological interactions necessitates further optimization to maximize therapeutic efficacy and safety. Emphasizing their roles in stability, drug loading, and performance, this review analyzes formulation strategies including oil phase selection, surfactant-co-surfactant optimization based on HLB values, and polymer selection for gel matrices. Additionally, mechanistic pathways of skin permeation are discussed. Moreover, recent advances in nanoemulgel-based delivery systems for natural bioactive compounds and their diverse biomedical applications in dermatological disorders, anti-inflammatory therapies, and anticancer drug delivery are highlighted, along with registered patents.

Graphical Abstract