title: Effect of pirfenidone delivered using layer-by-layer thin film on excisional wound healing.
abstract: The aim of this study was to evaluate the effect of a new anti-fibrotic agent, pirfenidone (PFD), delivered using polyelectrolyte multilayer films on excisional wound healing. Polyelectrolyte multilayer films were prepared by layer-by-layer (LbL) sequential adsorption of chitosan and sodium alginate. The UV-spectrophotometer, FTIR and differential scanning calorimeter were used to characterize the LbL thin films. The PFD was entrapped within the LbL thin films and its effect on excisional wound healing was studied in C57BL/6. The total protein, collagen content and TGF-β expression within the wound tissue were determined after application of PFD using LbL thin films, chitosan hydrogel and polyethylene glycol hydrogel. UV-spectrophotometer and FTIR studies showed a sequential adsorption of chitosan and alginate polymer layers to form LbL thin films. The thickness of LbL thin films with 15 bilayers was found to be 15 ± 2 μm. HPLC analysis showed a PFD loading efficiency of 1.0 ± 0.1mg in 1cm(2) area of LbL thin film. In vivo wound healing studies in C57BL/6 mice showed an accelerated (<9 days) wound contraction after treatment with the PFD compared with blank LbL thin film and commercial povidone-iodine gel (12 days). The collagen content within the wound tissue was significantly (p<0.05) less after treatment with PFD compared with blank film application. Western blot analysis showed gradual decrease in TGF-β expression within the wound tissue after treatment with PFD. This study for the first time demonstrated that new anti-fibrotic agent PFD loaded in LbL thin films can be utilized for excisional wound healing.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Mandapalli
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Labala
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bojja
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad 500078, Telangana, India. Electronic address: vamsi@hyderabad.bits-pilani.ac.in.
authors.forename: Venkata Vamsi Krishna
authors.initials: VV
authors.lastname: Venuganti
mesh_terms: D000464:Alginates / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D048271:Chitosan / Q000008:administration & dosage / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D020723:Glucuronic Acid / Q000008:administration & dosage / Q000737:chemistry; D006603:Hexuronic Acids / Q000008:administration & dosage / Q000737:chemistry; D020100:Hydrogels / Q000008:administration & dosage / Q000737:chemistry; D008810:Mice, Inbred C57BL; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011206:Povidone-Iodine / Q000008:administration & dosage / Q000737:chemistry; D011728:Pyridones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006603:Hexuronic Acids; D020100:Hydrogels; D011728:Pyridones; D016212:Transforming Growth Factor beta; D011092:Polyethylene Glycols; D011206:Povidone-Iodine; D020723:Glucuronic Acid; D003094:Collagen; D048271:Chitosan; C093844:pirfenidone
keywords: Collagen; Excisional wound healing; Layer-by-layer films; Pirfenidone; TGF-beta expression