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Objective <p>This study evaluated the TRPV4-modulating potential of silymarin (SM) using <i>in-silico</i> and <i>in-vitro</i> assays and developed an optimized PLGA-PVA nanoparticle (NP) formulation for targeted pulmonary delivery.</p> Methods <p>Molecular docking and molecular dynamics simulations were performed to assess SM binding within TRPV4 channel domains. TRPV4 activity was evaluated through calcium-influx assays in A549 cells. To improve solubility and sustained lung delivery, SM was encapsulated in poly (lactic-co-glycolic acid) nanoparticles stabilized with polyvinyl alcohol. A central composite design optimized PLGA concentration, PVA concentration, and stirring speed to maximize entrapment efficiency (EE) and control particle size. The optimized formulation was characterized by DLS, zeta potential, SEM, and BET surface analysis.</p> Results <p>Docking and simulation studies demonstrated stable SM-TRPV4 binding through multiple hydrogen bonds and hydrophobic interactions. Calcium-influx assays confirmed a dose-dependent reduction in intracellular Ca²⁺, consistent with TRPV4 inhibition. The optimized PLGA-PVA-SM NPs showed a mean particle size of 621.5 ± 7.27&#xa0;nm, zeta potential of − 31 mV, EE of 69.6 ± 0.11%, spherical morphology, and a mesoporous structure supporting sustained drug release.</p> Conclusions <p>SM exhibits potent TRPV4-modulating activity, and its encapsulation in PLGA-PVA NPs provides a stable, mesoporous carrier for pulmonary delivery. This nanocarrier system offers sustained release, improved solubility, and targeted lung deposition, representing a promising therapeutic strategy for TRPV4-related pulmonary disorders.</p> Graphical Abstract <p></p>

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Development and Optimization of PLGA-PVA Nanoparticles Encapsulating Silymarin for Pulmonary Delivery and TRPV4 Modulation

  • 期刊论文

  • 发表日期：

    2026年4月18日

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  • Mohit Kumar,
  • Md. Kamaruz Zaman,
  • Pakter Niri,
  • Subramanyam Polopalli,
  • Piya Adhikari,
  • Amartya Banerjee,
  • Ajay Kakati,
  • Shriyansh Srivastava,
  • Danswrang Goyary,
  • Yangchen Doma Bhutia,
  • Sanjeev Karmakar,
  • Sumit Kishor,
  • Saidur Rahaman,
  • Pronobesh Chattopadhyay

摘要

Objective

This study evaluated the TRPV4-modulating potential of silymarin (SM) using in-silico and in-vitro assays and developed an optimized PLGA-PVA nanoparticle (NP) formulation for targeted pulmonary delivery.

Methods

Molecular docking and molecular dynamics simulations were performed to assess SM binding within TRPV4 channel domains. TRPV4 activity was evaluated through calcium-influx assays in A549 cells. To improve solubility and sustained lung delivery, SM was encapsulated in poly (lactic-co-glycolic acid) nanoparticles stabilized with polyvinyl alcohol. A central composite design optimized PLGA concentration, PVA concentration, and stirring speed to maximize entrapment efficiency (EE) and control particle size. The optimized formulation was characterized by DLS, zeta potential, SEM, and BET surface analysis.

Results

Docking and simulation studies demonstrated stable SM-TRPV4 binding through multiple hydrogen bonds and hydrophobic interactions. Calcium-influx assays confirmed a dose-dependent reduction in intracellular Ca²⁺, consistent with TRPV4 inhibition. The optimized PLGA-PVA-SM NPs showed a mean particle size of 621.5 ± 7.27 nm, zeta potential of − 31 mV, EE of 69.6 ± 0.11%, spherical morphology, and a mesoporous structure supporting sustained drug release.

Conclusions

SM exhibits potent TRPV4-modulating activity, and its encapsulation in PLGA-PVA NPs provides a stable, mesoporous carrier for pulmonary delivery. This nanocarrier system offers sustained release, improved solubility, and targeted lung deposition, representing a promising therapeutic strategy for TRPV4-related pulmonary disorders.

Graphical Abstract