Abstract <p>A dual-drug transdermal delivery system was developed by co-encapsulating Panax notoginseng total saponins (PNS) and Aconitum alkaloids into lipidic cubic nanoparticles (LCNPs) and incorporating them into dissolving microneedles (DMNs). High-performance liquid chromatography (HPLC) methods were established and validated for simultaneous quantification of representative notoginsenosides and Aconitum alkaloids, showing high specificity, excellent linearity (<InlineEquation ID="IEq1"> <EquationSource Format="TEX">$R^2 > 0.999$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <msup> <mi>R</mi> <mn>2</mn> </msup> <mo>></mo> <mn>0.999</mn> </mrow> </math></EquationSource> </InlineEquation>), good precision (RSD < 3%), and satisfactory accuracy (recoveries 95–105%). LCNPs prepared via a precursor injection method exhibited a mean particle size of <InlineEquation ID="IEq2"> <EquationSource Format="TEX">$56.9 \pm 3.2$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mn>56.9</mn> <mo>±</mo> <mn>3.2</mn> </mrow> </math></EquationSource> </InlineEquation> nm with a narrow size distribution (PDI = 0.272) and high encapsulation efficiencies (> 90%). Transmission electron microscopy confirmed the fingerprint-like cubic nanostructure. The LCNP-loaded DMNs possessed sufficient mechanical strength to penetrate skin and rapidly dissolved within 20 min. In vitro permeation studies showed cumulative permeation of 96.9% for PNS and 93.9% for Aconitum alkaloids within 6 h, markedly higher than LCNPs alone (< 20% at 24 h). In vivo, the LCNP–DMN system significantly reduced acetic acid–induced writhing in mice (<InlineEquation ID="IEq3"> <EquationSource Format="TEX">$P < 0.05$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo><</mo> <mn>0.05</mn> </mrow> </math></EquationSource> </InlineEquation>) and alleviated formaldehyde-induced arthritis in rats, with decreased joint swelling and reduced pro-inflammatory cytokines (IL-1<InlineEquation ID="IEq4"> <EquationSource Format="TEX">$\beta $</EquationSource> <EquationSource Format="MATHML"><math> <mi>β</mi> </math></EquationSource> </InlineEquation>, TNF-<InlineEquation ID="IEq5"> <EquationSource Format="TEX">$\alpha $</EquationSource> <EquationSource Format="MATHML"><math> <mi>α</mi> </math></EquationSource> </InlineEquation>, IL-6; <InlineEquation ID="IEq6"> <EquationSource Format="TEX">$P<0.01$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mi>P</mi> <mo><</mo> <mn>0.01</mn> </mrow> </math></EquationSource> </InlineEquation>), comparable to a commercial external patch. No visible dermal irritation or systemic toxicity was observed. Overall, the PNS–Aconitum LCNP–DMN system enabled synchronized dual-drug delivery with strong anti-inflammatory and analgesic efficacy and good biocompatibility, representing a promising nanostructured transdermal platform for the management of inflammatory pain conditions such as arthritis.</p> Graphical Abstract <p></p>

Development and Characterization of Ginsenoside-Aconitum Lipidic Cubic Nanoparticle-Loaded Dissolving Microneedles for Enhanced Transdermal Anti-inflammatory Therapy

期刊论文
发表日期：

2026年5月13日

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Yang Liu,
Yaqian Wang,
Sinan Wu,
Xiali Zhu,
Jie Yang,
Yongyan Jia

摘要

Abstract

A dual-drug transdermal delivery system was developed by co-encapsulating Panax notoginseng total saponins (PNS) and Aconitum alkaloids into lipidic cubic nanoparticles (LCNPs) and incorporating them into dissolving microneedles (DMNs). High-performance liquid chromatography (HPLC) methods were established and validated for simultaneous quantification of representative notoginsenosides and Aconitum alkaloids, showing high specificity, excellent linearity ( $R^2 > 0.999$ $R^{2} > 0.999$ ), good precision (RSD < 3%), and satisfactory accuracy (recoveries 95–105%). LCNPs prepared via a precursor injection method exhibited a mean particle size of $56.9 \pm 3.2$ $56.9 \pm 3.2$ nm with a narrow size distribution (PDI = 0.272) and high encapsulation efficiencies (> 90%). Transmission electron microscopy confirmed the fingerprint-like cubic nanostructure. The LCNP-loaded DMNs possessed sufficient mechanical strength to penetrate skin and rapidly dissolved within 20 min. In vitro permeation studies showed cumulative permeation of 96.9% for PNS and 93.9% for Aconitum alkaloids within 6 h, markedly higher than LCNPs alone (< 20% at 24 h). In vivo, the LCNP–DMN system significantly reduced acetic acid–induced writhing in mice ( $P < 0.05$ $P < 0.05$ ) and alleviated formaldehyde-induced arthritis in rats, with decreased joint swelling and reduced pro-inflammatory cytokines (IL-1 $\beta $ $β$ , TNF- $\alpha $ $α$ , IL-6; $P<0.01$ $P < 0.01$ ), comparable to a commercial external patch. No visible dermal irritation or systemic toxicity was observed. Overall, the PNS–Aconitum LCNP–DMN system enabled synchronized dual-drug delivery with strong anti-inflammatory and analgesic efficacy and good biocompatibility, representing a promising nanostructured transdermal platform for the management of inflammatory pain conditions such as arthritis.

Graphical Abstract