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<p>Artemether (AE), which is a highly active antimalarial possessing newly found neuro‑protective potential, suffers from low aqueous solubility, high first‑pass metabolism, and minimal blood–brain‑barrier (BBB) penetration. The research aimed at developing an in-situ gel with AE-loaded solid lipid nanoparticles (SLNs) and optimizing it employing a 3² complete factorial design. Glyceryl monostearate (GMS)‑based SLNs were prepared by high‑pressure homogenization (HPH) (356.9 ± 2.3&#xa0;nm; PDI 0.442; ζ‑potential − 16.7 mV; entrapment efficiency 86.5 ± 1.5%). Lyophilized nanoparticles retained spherical shape, structural integrity, and a shifted DSC endotherm at 62.2&#xa0;°C, establishing molecular dispersion of AE. In situ gels were developed using gellan gum (0.30–0.50% w/v) and Carbopol 934P (0.05–0.25% w/v). Design‑Expert<sup>®</sup> revealed an optimum formulation composition of 0.36% gellan gum + 0.14% Carbopol, providing viscosity 548 ± 12 CP, mucoadhesive strength 701 ± 17 dyne cm⁻², and 93.0 ± 1.1% cumulative release in 6&#xa0;h. Release kinetics obeyed the Higuchi model (R² 0.981) with a Korsmeyer–Peppas exponent 1.08, demonstrating super‑case‑II transport regulated through diffusion and polymer relaxation. Ex vivo permeation through goat nasal mucosa reflected an 8.3‑fold increase in flux compared to plain AE, while a one‑month accelerated‑stability study validated physicochemical stability. Together, these results show that an ion-activated, SLN-loaded gellan–Carbopol matrix can release AE in a sustained form and significantly increase nose-to-brain permeation, presenting an appealing platform for both antimalarial and neuro-therapeutic uses.</p>

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Development of a Gellan–Carbopol in Situ Gel System for Intranasal Delivery of Artemether-Loaded SLNs: Optimization and Kinetic Evaluation

  • 期刊论文

  • 发表日期：

    2025年12月27日

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  • Harish Bhute,
  • Pramod S. Salve,
  • Sameer Sheikh,
  • Ujban Md Hussain,
  • Samiksha Tammewar,
  • Amol A. Tatode,
  • Mohammad Qutub,
  • Tanvi Premchandani

摘要

Artemether (AE), which is a highly active antimalarial possessing newly found neuro‑protective potential, suffers from low aqueous solubility, high first‑pass metabolism, and minimal blood–brain‑barrier (BBB) penetration. The research aimed at developing an in-situ gel with AE-loaded solid lipid nanoparticles (SLNs) and optimizing it employing a 3² complete factorial design. Glyceryl monostearate (GMS)‑based SLNs were prepared by high‑pressure homogenization (HPH) (356.9 ± 2.3 nm; PDI 0.442; ζ‑potential − 16.7 mV; entrapment efficiency 86.5 ± 1.5%). Lyophilized nanoparticles retained spherical shape, structural integrity, and a shifted DSC endotherm at 62.2 °C, establishing molecular dispersion of AE. In situ gels were developed using gellan gum (0.30–0.50% w/v) and Carbopol 934P (0.05–0.25% w/v). Design‑Expert® revealed an optimum formulation composition of 0.36% gellan gum + 0.14% Carbopol, providing viscosity 548 ± 12 CP, mucoadhesive strength 701 ± 17 dyne cm⁻², and 93.0 ± 1.1% cumulative release in 6 h. Release kinetics obeyed the Higuchi model (R² 0.981) with a Korsmeyer–Peppas exponent 1.08, demonstrating super‑case‑II transport regulated through diffusion and polymer relaxation. Ex vivo permeation through goat nasal mucosa reflected an 8.3‑fold increase in flux compared to plain AE, while a one‑month accelerated‑stability study validated physicochemical stability. Together, these results show that an ion-activated, SLN-loaded gellan–Carbopol matrix can release AE in a sustained form and significantly increase nose-to-brain permeation, presenting an appealing platform for both antimalarial and neuro-therapeutic uses.