Innovated pirfenidone loaded lecithin nanocapsules for targeting liver fibrosis: Formulation, characterization and in vivo study

• Published in: International journal of pharmaceutics Vol. 631; p. 122539
• Main Authors: AbouSamra, Mona M., Elgohary, Rania, Mansy, Soheir S.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25-01-2023
• Subjects: Animals; Electron microscopy; Hepatic biomarkers; Lecithin nanocapsules; Lecithins; Liver Cirrhosis - drug therapy; Liver fibrosis; Liver targeting; Mice; Nanocapsules; Pirfenidone; Pyridones - pharmacokinetics; Tissue Distribution; Liver targeting; Liver fibrosis; Pirfenidone; Electron microscopy; Lecithin nanocapsules; Hepatic biomarkers
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.122539

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Increasing interest in developing antifibrotic therapies became a paramount priority due to the globally raised incidence of deaths secondary to hepatic cirrhosis.
This work deals with the development of innovative antifibrotic pirfenidone -loaded lecithin core nanocapsules. This with the intention to target the liver and to increase the drug bioavailability, reducing drug liver toxicity, and studying the associated hepatic microenvironment changes.
PFD-loaded lecithin nanocapsules (PFD-LENCs) were prepared using the natural lipoid S45 for its dual benefits of being both a lipid and an amphiphilic surfactant. The selected formulation exhibited in vitro sustained drug release up to 24 h compared to free PFD, which is consistent with the studied pharmacokinetic profile. The studied cytotoxicity of PFD as well as PFD-LENCs exhibited negligible cytotoxicity in normal oral epithelial cells. For exploring the capability of the PFD-LENCs in reaching the liver; in vivo tracing using CLSM, in vivo biodistribution to the vital organs were conducted and electron microscopic examination for depicting nanoparticles in liver tissue was performed. Results revealed the capability of the prepared fluorescent LENC2 in reaching the liver, PFD-LENCs detection in the Disse space of the liver and the significant accumulation of PFD-LENCs in liver tissue compared to the other tested organs. The assessment of the necro-inflammatory, antioxidant and the anti-fibrotic effect of PFD-LENCs (50 & 100 mg/kg) exhibited a significant decrease of liver enzymes, TNF-α, TGF-β, Col-1, α-SMA, and TIMP-1, and a significant increase of catalase enzyme and MMP2 compared to free PFD. EM studies, revealed often detection of dendritic cells in PFD-LENCs (100 mg/kg) treated mice and abnormal collagen structure which can represent an adjunct contribution to the antifibrotic mechanism of PFD-LENCs.
In conclusion, the development of this innovative PFD loaded lecithin nanocapsules achieved a targeting ability to the liver, controlled drug release, thereby increase the PFD therapeutic value in downregulating hepatic fibrosis in adjunct with the reduction of liver toxicity.