This study focuses on formulating and optimizing Polyherbal Nanoethosomes for controlled drug delivery, utilizing a polyherbal extract comprising Basella alba L., Portulaca oleracea L., Lawsonia inermis L., Trigonella foenum L., and Peristrophe paniculata L. Comprehensive characterization revealed a variety of secondary metabolites within the extract. The primary goal was to create poly herbal extract-entrapped ethosomes that could be integrated into a sustained-release transdermal gel dosage. We prepared nanoethosomes using phosphatidylcholine, ethanol, Tween 80, and SLS, and optimized them using Design Expert software. The characteristics included size (particle size: 121 ± 2.60 nm) and entrapment efficiency (81.91 ± 1.92%), followed by incorporation into a carbopol gel for skin application. We performed in-vitro permeation studies and cytotoxic assays on L-929 cells, which revealed favorable outcomes. Optimized nanoethosomes displayed desirable particle characteristics, highlighting their potential for controlled drug delivery. The nano vesicular gels had good rheological and physical properties (polydispersity index: 0.41 ± 0.04, zeta potential: -8.12 ± 1.25 mV), which meant they could be used topically. This research underscores the compatibility of plant extracts with formulation components, offering a foundation for Polyherbal Nanoethosomes in pharmaceutical formulations. The study emphasizes precise control over particle attributes and suggests potential applications in enhancing drug release and bioavailability.
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