Chitosan self-assembled polymeric nanoparticles for percutaneous delivery of betamethasone in contact dermatitis

Drug Dev Ind Pharm. 2021 Aug;47(8):1310-1317. doi: 10.1080/03639045.2021.1989457. Epub 2021 Oct 15.

Abstract

Objective: The study was performed with an aim to investigate the efficiency of two treatment options in experimental nickel-induced contact dermatitis (CT), with either betamethasone or chitosan cross-linked nano-encapsulated betamethasone lanoline solutions (nano-betamethasone).

Methods: Male Wistar rats were used. The differences were compared based on lesion visual appearance, skinfold thickness, white blood cell count (WBC), erythrocyte sedimentation rate (ESR), blood serum prooxidant-antioxidant balance (thiobarbituric acid reactive substances, TBARS; supersoxide dismutase, SOD; catalase, KAT), blood cytokine profile (TNF-α, IL-1β, IL-10, and IL-4), and histological examination of affected skin.

Results: All animals treated with nickel sulfate developed CT and systemic inflammatory response on day 12, which only slightly lessened, if left untreated, on day 20. The therapeutic effectiveness of nano-betamethasone was significantly far superior (p < 0.01) compared to betamethasone. Specifically, the visual appearance of lesion severity of betamethasone vs. nano-betamethasone ± SD was 1.82 ± 0.18 vs. 1.17 ± 0.24 points, skinfold thickness-2.68 ± 0.12 vs. 2.12 ± 0.10 mm, ESR-6.38 ± 0.27 vs. 5.12 ± 0.20 mm/h, WBC-8.47 ± 0.28 vs. 7.17 ± 0.24 109/L, TBARS-1.09 ± 0.04 vs. 0.94 ± 0.02 µmol/L, SOD-3.38 ± 0.26 vs. 4.12 ± 0.18 r.u./L, KAT-11.54 ± 0.14 vs. 10.02 ± 0.19 mkatal/L, respectively. The nano-betamethasone formulation was also more effective (p < 0.01) in increasing anti-inflammatory cytokines level, IL-10 (8.96 ± 0.32 vs. 7.54 ± 0.52 pg/mL) and IL-4 (13.16 ± 0.45 vs. 11.43 ± 0.58 pg/mL); and decreasing in pro-inflammatory TNF-α (20.94 ± 2.30 vs. 26.98 ± 1.16 pg/mL) and IL-1β (19.35 ± 1.28 vs. 24.77 ± 1.75 pg/mL), respectively. These findings were also supported with histological examination.

Conclusions: Nano-betamethasone may be considered as a more successful transcutaneous therapy for managing contact dermatitis compared to ointments consisting of betamethasone in traditional form.

Keywords: Chitosan nanoparticles; betamethasone; contact dermatitis; cytokines; prooxidant-antioxidant balance; skin histology.

MeSH terms

  • Animals
  • Betamethasone
  • Chitosan*
  • Dermatitis, Contact*
  • Interleukin-10
  • Interleukin-4
  • Male
  • Nanoparticles*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha

Substances

  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-4
  • Chitosan
  • Betamethasone
  • Superoxide Dismutase