1Department of Pharmaceutics, Srinath college of pharmacy, Bajajnagar waluj MIDC, Chhatrapati Sambhajinagar, Maharashtra, 431136.
2Department of Pharmaceutical Chemistry, Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Parul University, Waghodiya, Limda Vadodara-391760, Gujarat, India.
3*Department of Biochemistry, Adhiparasakthi College of Arts and Science, (Autonomous), G. B. Nagar, Kalavai - 632 506, Ranipet District, Tamil Nadu.
4Department of Pharmacology, Institute of Pharmaceutical Sciences, Faculty of Pharmacy, Parul University, Waghodiya, Limda Vadodara-391760, Gujarat, India.
5Faculty of Pharmacy, IFTM University Lodhipur Rajput, NH-24, Delhi Road Moradabad, UP, 244102.
6SAM College of Pharmacy, Faculty of Pharmacy, SAM Global University, Raisen (Madhya Pradesh) India-464551.
7Prasad Institute of Technology Department of Pharmacy Punch Hattia Sadr Jaunpur U.P. Pin Code-222001.
8Department of Pharmacology, School of Pharmacy, GH Raisoni, Skill Tech University, Nagpur- 440016.
Background: Chronic inflammatory diseases are frequently associated with progressive fibrotic remodelling driven by oxidative stress, cytokine dysregulation, and excessive collagen deposition. Silibinin, a bioactive flavonolignan derived from Silybum marianum, exhibits potent antioxidant and anti-inflammatory properties; however, its clinical utility is limited by poor aqueous solubility and bioavailability.
Methods: In this study, silibinin-loaded polymeric nanoparticles were developed and optimised using a Quality by Design approach. The formulation was characterised for physicochemical properties, in vitro release behaviour, and stability. Mechanistic evaluations were conducted in macrophage and fibroblast cell models to assess modulation of oxidative stress, inflammatory cytokine production, and collagen synthesis under stimulated conditions.
Results: The optimised formulation exhibited nanoscale particle size, high entrapment efficiency, and sustained drug release. Silibinin nanoparticles significantly reduced intracellular reactive oxygen species, restored endogenous antioxidant levels, and suppressed pro-inflammatory mediators including TNF-α, IL-6, and nitric oxide. Furthermore, marked inhibition of collagen type I synthesis and total collagen deposition was observed in transforming growth factor-β1–stimulated fibroblasts. Across all assays, the nanoparticle formulation demonstrated superior efficacy compared to free silibinin.
Conclusion: The findings established that nanoparticle-enabled delivery substantially enhanced the anti-inflammatory and anti-fibrotic effects of silibinin through coordinated modulation of oxidative stress, cytokine signalling, and extracellular matrix accumulation, highlighting its therapeutic potential for chronic inflammatory and fibrotic disorders.
Keywords: Silibinin; anti-inflammatory; anti-fibrotic; oxidative stress; cytokines; nanoparticles.
How to cite this article: Sable PS, Wagh B, Sampath S, Nemade MA, Rani C, Durgashankar MP, Wasiullah M, Ekhankar AR. Nanotechnological Enhancement of Silibinin: Integrated Anti-Inflammatory and Anti-Fibrotic Mechanisms Targeting Oxidative Stress and Collagen Deposition. Int J Drug Deliv Technol. 2026;16(15s): 697-710. DOI: 10.25258/ijddt.16.15s.80
Source of support: Nil.
Conflict of interest: None