Scholarlink

<p>Lymphatic filariasis is a major neglected tropical disease that requires more effective therapeutic approaches with improved oral bioavailability and enhanced distribution to lymphoid tissues. In the present study, andrographolide-loaded nanostructured lipid carriers (AND-NLC) were developed and optimized to improve the oral delivery and antifilarial efficacy of andrographolide. The formulation was prepared using a melt emulsification–ultrasonication method and optimized through a Box–Behnken design approach. The optimized AND-NLC exhibited a particle size of 97.80 ± 0.37&#xa0;nm, a narrow particle size distribution (PDI 0.177 ± 0.01), zeta potential of − 28.2 ± 0.72 mV, and entrapment efficiency of 88.72 ± 0.47%. Differential scanning calorimetry and X-ray diffraction analyses suggested successful incorporation of andrographolide within the lipid matrix with reduced drug crystallinity, while transmission electron microscopy confirmed the formation of nearly spherical nanoparticles with uniform nanosized distribution. The optimized formulation demonstrated sustained <i>in vitro</i> drug release and satisfactory physicochemical stability during storage. Pharmacokinetic studies revealed significantly enhanced systemic exposure following oral administration of AND-NLC compared with andrographolide suspension (AND-Susp), with higher C<sub>max</sub> (4.51 ± 0.31 vs. 0.82 ± 0.39&#xa0;µg/mL), delayed T<sub>max</sub> (3.0 ± 0.29 vs. 0.5 ± 0.54&#xa0;h), and improved relative bioavailability (1.35-fold). Biodistribution and confocal laser scanning microscopy studies demonstrated greater accumulation of andrographolide within lymphoid tissues, providing indirect evidence of enhanced lymphatic distribution and improved tissue uptake. Furthermore, AND-NLC exhibited enhanced <i>in vitro</i> and <i>in vivo</i> antifilarial activity against <i>Brugia malayi</i>, including improved microfilaricidal, macrofilaricidal, and embryostatic effects compared with AND-Susp. Overall, the developed AND-NLC system demonstrated promising potential as an oral lipid-based nanocarrier for improving the bioavailability, lymphoid tissue distribution, and antifilarial efficacy of andrographolide, thereby warranting further investigation for the management of lymphatic filariasis.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Andrographolide-Loaded Nanostructured Lipid Carriers with Potential for Enhanced Lymphatic Distribution: Formulation, Characterization, and Antifilarial Evaluation

  • 期刊论文

  • 发表日期：

    2026年7月22日

查看全文
  • Saurabh Shrivastava,
  • Chanchal Deep Kaur,
  • Suman Shrivastava

摘要

Lymphatic filariasis is a major neglected tropical disease that requires more effective therapeutic approaches with improved oral bioavailability and enhanced distribution to lymphoid tissues. In the present study, andrographolide-loaded nanostructured lipid carriers (AND-NLC) were developed and optimized to improve the oral delivery and antifilarial efficacy of andrographolide. The formulation was prepared using a melt emulsification–ultrasonication method and optimized through a Box–Behnken design approach. The optimized AND-NLC exhibited a particle size of 97.80 ± 0.37 nm, a narrow particle size distribution (PDI 0.177 ± 0.01), zeta potential of − 28.2 ± 0.72 mV, and entrapment efficiency of 88.72 ± 0.47%. Differential scanning calorimetry and X-ray diffraction analyses suggested successful incorporation of andrographolide within the lipid matrix with reduced drug crystallinity, while transmission electron microscopy confirmed the formation of nearly spherical nanoparticles with uniform nanosized distribution. The optimized formulation demonstrated sustained in vitro drug release and satisfactory physicochemical stability during storage. Pharmacokinetic studies revealed significantly enhanced systemic exposure following oral administration of AND-NLC compared with andrographolide suspension (AND-Susp), with higher Cmax (4.51 ± 0.31 vs. 0.82 ± 0.39 µg/mL), delayed Tmax (3.0 ± 0.29 vs. 0.5 ± 0.54 h), and improved relative bioavailability (1.35-fold). Biodistribution and confocal laser scanning microscopy studies demonstrated greater accumulation of andrographolide within lymphoid tissues, providing indirect evidence of enhanced lymphatic distribution and improved tissue uptake. Furthermore, AND-NLC exhibited enhanced in vitro and in vivo antifilarial activity against Brugia malayi, including improved microfilaricidal, macrofilaricidal, and embryostatic effects compared with AND-Susp. Overall, the developed AND-NLC system demonstrated promising potential as an oral lipid-based nanocarrier for improving the bioavailability, lymphoid tissue distribution, and antifilarial efficacy of andrographolide, thereby warranting further investigation for the management of lymphatic filariasis.

Graphical Abstract