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Purpose <p>Polycaprolactone nanoparticles (PCLNPs) are biodegradable carriers widely investigated for drug delivery applications. Their hydrophobic nature and high encapsulation efficiency make them ideal for sustained drug release. This study aimed to encapsulate licofelone (LF), a dual COX/5-LOX inhibitor, within PCLNPs to enhance its therapeutic efficacy for osteoarthritis treatment through transdermal administration.</p> Methods <p>LF loaded PCLNPs were formulated using the nanoprecipitation method. A 2<sup>3</sup> full factorial design was employed by varying PCL (100 or 150&#xa0;mg), PVA (150 or 300&#xa0;mg), and SDC (10 or 20&#xa0;mg) at two levels each. The optimum formula was F8, consisting of 150&#xa0;mg PCL, 300&#xa0;mg PVA, and 20&#xa0;mg SDC.</p> Results <p>F8 formulation exhibited a spherical shape with a particle size (PS) of 269.3 ± 1.90&#xa0;nm, an encapsulation efficiency (EE%) of 89 ± 0.56%, a polydispersity index (PDI) of 0.21 ± 0.02, and a zeta potential (ZP) of -27.85 ± 0.07 mV. The F8 gel exhibited a sustained-release profile, with drug permeation across excised rat skin 2.47-fold higher than that of the LF gel (<i>n</i> = 3, <i>p</i> &lt; 0.05). In vivo evaluation revealed significant chondroprotective and regenerative effects in a monoiodoacetate (MIA)-induced osteoarthritis rat model. F8 gel suppressed the release of inflammatory and pain mediators (5-LOX, COX, LTB<sub>4</sub>, and PGE2) and serum cartilage degradation products (CTX-II and COMP) after 10 days of treatment. Histological evaluation further confirmed its ability to prevent cartilage surface depletion and matrix loss.</p> Conclusion <p>The optimized F8 gel achieved sustained LF release for approximately 20&#xa0;h, enhanced ex vivo permeation by 2.47-fold relative to LF gel, and significantly reduced inflammatory mediators and cartilage degradation markers in vivo, highlighting its potential as a promising transdermal therapy for osteoarthritis management.</p> Graphical Abstract <p></p>

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Polycaprolactone Nanoparticles Boost Licofelone Transdermal Delivery for Osteoarthritis: In Vitro Characterization, Ex Vivo Permeability, and In Vivo Efficacy

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Khaled E. Abuelella,
  • Shaimaa Mosallam,
  • Amira A. El-Gazar,
  • Ahmed Hassen Elshafeey,
  • Sara M. Soliman

摘要

Purpose

Polycaprolactone nanoparticles (PCLNPs) are biodegradable carriers widely investigated for drug delivery applications. Their hydrophobic nature and high encapsulation efficiency make them ideal for sustained drug release. This study aimed to encapsulate licofelone (LF), a dual COX/5-LOX inhibitor, within PCLNPs to enhance its therapeutic efficacy for osteoarthritis treatment through transdermal administration.

Methods

LF loaded PCLNPs were formulated using the nanoprecipitation method. A 23 full factorial design was employed by varying PCL (100 or 150 mg), PVA (150 or 300 mg), and SDC (10 or 20 mg) at two levels each. The optimum formula was F8, consisting of 150 mg PCL, 300 mg PVA, and 20 mg SDC.

Results

F8 formulation exhibited a spherical shape with a particle size (PS) of 269.3 ± 1.90 nm, an encapsulation efficiency (EE%) of 89 ± 0.56%, a polydispersity index (PDI) of 0.21 ± 0.02, and a zeta potential (ZP) of -27.85 ± 0.07 mV. The F8 gel exhibited a sustained-release profile, with drug permeation across excised rat skin 2.47-fold higher than that of the LF gel (n = 3, p < 0.05). In vivo evaluation revealed significant chondroprotective and regenerative effects in a monoiodoacetate (MIA)-induced osteoarthritis rat model. F8 gel suppressed the release of inflammatory and pain mediators (5-LOX, COX, LTB4, and PGE2) and serum cartilage degradation products (CTX-II and COMP) after 10 days of treatment. Histological evaluation further confirmed its ability to prevent cartilage surface depletion and matrix loss.

Conclusion

The optimized F8 gel achieved sustained LF release for approximately 20 h, enhanced ex vivo permeation by 2.47-fold relative to LF gel, and significantly reduced inflammatory mediators and cartilage degradation markers in vivo, highlighting its potential as a promising transdermal therapy for osteoarthritis management.

Graphical Abstract