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<p>Psoriasis, a persistent inflammatory skin condition, requires localized treatments to reduce systemic effects and improve therapeutic outcomes. To meet this need, the current investigation developed a specialized pH-responsive nanogel (FA-NG) loaded with the corticosteroid fluocinolone acetonide (FA). This nanogel utilizes N, N,N-trimethyl chitosan (TMC), a quaternized form of chitosan (CS) known for its enhanced pH responsiveness and solubility. The design capitalizes on the natural pH difference between healthy skin (pH 6.0) and psoriatic lesions (pH 4.0), enabling FA-NG to release its payload specifically at the diseased site. Optimization of the formulation was achieved using a 3-factor, 3-level Box-Behnken design. This process resulted in nanogels characterized by a small particle size of 102.51 ± 1.21 nanometers, a low polydispersity index (PDI) indicating good uniformity, a positive zeta potential of + 31.15 mV promoting skin interaction, and a high drug entrapment efficiency (EE). Subsequent in vitro release data demonstrated sustained delivery of FA over 36&#xa0;h. Crucially, a markedly greater release was observed at pH 4.0 of psoriatic skin compared to pH 6.0, confirming the pH-responsive behavior of FA-NG. Evaluation in an imiquimod-induced psoriasis mice model revealed the in vivo effectiveness of FA-NG, showing significant reductions in key disease markers in psoriasis. Confocal microscopy confirmed enhanced penetration depth of FA-NG into the skin layers. Furthermore, MTT assay indicated selective cytotoxicity towards keratinocytes, the primary skin cells affected in psoriasis. Supporting the therapeutic effect, immunohistochemical and biochemical analyses demonstrated that FA-NG effectively suppressed levels of critical inflammatory cytokines and reduced the infiltration of CD3 + T-cells, highlighting its immunosuppressive capability. Skin irritation studies confirmed the non-irritating nature of the FA-NG, validating the safety profile. Taken together, these comprehensive results establish FA-loaded TMC nanogel as a highly promising pH-responsive drug delivery platform for targeted psoriasis management.</p>

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pH Responsive Trimethyl Chitosan Nanogels Enhance Site-Specific Fluocinolone Acetonide Delivery for Psoriasis Therapy

  • 期刊论文

  • 发表日期：

    2026年2月16日

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  • Apeksha Gupta,
  • Kanchan Kohli,
  • Showkat R. Mir,
  • Rahmuddin Khan,
  • Abdulsalam Alhalmi,
  • Saima Amin

摘要

Psoriasis, a persistent inflammatory skin condition, requires localized treatments to reduce systemic effects and improve therapeutic outcomes. To meet this need, the current investigation developed a specialized pH-responsive nanogel (FA-NG) loaded with the corticosteroid fluocinolone acetonide (FA). This nanogel utilizes N, N,N-trimethyl chitosan (TMC), a quaternized form of chitosan (CS) known for its enhanced pH responsiveness and solubility. The design capitalizes on the natural pH difference between healthy skin (pH 6.0) and psoriatic lesions (pH 4.0), enabling FA-NG to release its payload specifically at the diseased site. Optimization of the formulation was achieved using a 3-factor, 3-level Box-Behnken design. This process resulted in nanogels characterized by a small particle size of 102.51 ± 1.21 nanometers, a low polydispersity index (PDI) indicating good uniformity, a positive zeta potential of + 31.15 mV promoting skin interaction, and a high drug entrapment efficiency (EE). Subsequent in vitro release data demonstrated sustained delivery of FA over 36 h. Crucially, a markedly greater release was observed at pH 4.0 of psoriatic skin compared to pH 6.0, confirming the pH-responsive behavior of FA-NG. Evaluation in an imiquimod-induced psoriasis mice model revealed the in vivo effectiveness of FA-NG, showing significant reductions in key disease markers in psoriasis. Confocal microscopy confirmed enhanced penetration depth of FA-NG into the skin layers. Furthermore, MTT assay indicated selective cytotoxicity towards keratinocytes, the primary skin cells affected in psoriasis. Supporting the therapeutic effect, immunohistochemical and biochemical analyses demonstrated that FA-NG effectively suppressed levels of critical inflammatory cytokines and reduced the infiltration of CD3 + T-cells, highlighting its immunosuppressive capability. Skin irritation studies confirmed the non-irritating nature of the FA-NG, validating the safety profile. Taken together, these comprehensive results establish FA-loaded TMC nanogel as a highly promising pH-responsive drug delivery platform for targeted psoriasis management.