<p>Wounds are breaks in the skin or tissues caused by trauma or surgery and require a complex healing process to restore integrity. Berberine hydrochloride (BRH), a BCS class III drug with antibacterial, anti-inflammatory and wound-healing properties, suffers from poor permeability and rapid clearance. To overcome these limitations, BRH was encapsulated in cubosomes and coated with mannosylated chitosan (MC) for targeted delivery through mannose receptors on activated macrophages at the wound site. Chitosan aids healing by reducing inflammation, stimulating fibroblast proliferation, supporting collagen synthesis, maintaining moisture and sustaining drug release. BRH-loaded cubosomes (BRH-CB) were optimized using a 3² factorial design with glyceryl monooleate (1–2%) and poloxamer 407 (0.1–0.3%) as variables, evaluating particle size, PDI and entrapment efficiency (EE). Optimized BRH-CB showed particle size 98.5 ± 0.41&#xa0;nm, PDI 0.230 ± 0.82, EE 93 ± 0.82% and zeta potential − 39.2 mV. XRD, DSC and FTIR confirmed drug incorporation. MC was synthesized by reductive amination and coated onto BRH-CB. The MC-BRH-CB formulation displayed particle size 157.1 ± 3.50&#xa0;nm, PDI 0.302 ± 0.10 and zeta potential + 28.2 mV, and was incorporated into a Carbopol 934 hydrogel. The prepared MC-BRH-CB hydrogel showed sustained drug release, enhanced permeation and drug retention. In-vivo studies showed superior wound healing compared with plain BRH gel. After 15 days, % wound contraction was 98.86 ± 0.92% with MC-BRH-CB hydrogel, versus 85.75 ± 0.58% (BRH gel) and 68.39 ± 1.64% (control). Three-month stability tests confirmed the MC-BRH-CB hydrogel as a promising strategy for effective wound management.</p>

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Mannosylated Chitosan–Coated Berberine Hydrochloride Cubosomal Hydrogel for Targeted Macrophage-Mediated Wound Healing

  • Rushikesh Rupanavar,
  • Manoj Shinde,
  • Varsha Mane,
  • Avinash Bhosale

摘要

Wounds are breaks in the skin or tissues caused by trauma or surgery and require a complex healing process to restore integrity. Berberine hydrochloride (BRH), a BCS class III drug with antibacterial, anti-inflammatory and wound-healing properties, suffers from poor permeability and rapid clearance. To overcome these limitations, BRH was encapsulated in cubosomes and coated with mannosylated chitosan (MC) for targeted delivery through mannose receptors on activated macrophages at the wound site. Chitosan aids healing by reducing inflammation, stimulating fibroblast proliferation, supporting collagen synthesis, maintaining moisture and sustaining drug release. BRH-loaded cubosomes (BRH-CB) were optimized using a 3² factorial design with glyceryl monooleate (1–2%) and poloxamer 407 (0.1–0.3%) as variables, evaluating particle size, PDI and entrapment efficiency (EE). Optimized BRH-CB showed particle size 98.5 ± 0.41 nm, PDI 0.230 ± 0.82, EE 93 ± 0.82% and zeta potential − 39.2 mV. XRD, DSC and FTIR confirmed drug incorporation. MC was synthesized by reductive amination and coated onto BRH-CB. The MC-BRH-CB formulation displayed particle size 157.1 ± 3.50 nm, PDI 0.302 ± 0.10 and zeta potential + 28.2 mV, and was incorporated into a Carbopol 934 hydrogel. The prepared MC-BRH-CB hydrogel showed sustained drug release, enhanced permeation and drug retention. In-vivo studies showed superior wound healing compared with plain BRH gel. After 15 days, % wound contraction was 98.86 ± 0.92% with MC-BRH-CB hydrogel, versus 85.75 ± 0.58% (BRH gel) and 68.39 ± 1.64% (control). Three-month stability tests confirmed the MC-BRH-CB hydrogel as a promising strategy for effective wound management.