title: Layer-by-Layer Thin Films for Co-Delivery of TGF-β siRNA and Epidermal Growth Factor to Improve Excisional Wound Healing.
abstract: The major challenge with treatment of dermal wounds is accelerating healing process, while preventing the scar formation. Herein, we have fabricated layer-by-layer (LbL) polyelectrolyte multilayer films containing epidermal growth factor (EGF) and TGF-β siRNA to improve excisional wound healing and decrease scar formation. The chitosan and sodium alginate LbL thin films showed 13.0 MPa tensile strength and 2.22 N/cm2skin adhesion strength. The LbL thin films were found to be cytocompatible, where A431 epidermal keratinocytes adhered to the film and showed 86.2 ± 0.8% cell growth compared with cells cultured in the absence of LbL thin film. In contrast, LbL thin film did not promote the Escherichia coli and Staphylococcus aureus bacterial colony formation. In a C57BL/6 mouse excisional wound model, application of LbL thin films containing TGF-β siRNA significantly (p < 0.05) reduced the TGF-β protein expression and collagen production. The LbL thin films containing EGF showed improved wound contraction (<9 days post excision). The co-delivery of TGF-β siRNA and EGF using LbL thin films resulted in accelerated wound healing and decreased collagen deposition. Furthermore, the LbL thin films with TGF-β siRNA and EGF combination showed greater reepithelialization. Taken together, we have successfully demonstrated the co-delivery of TGF-β siRNA and EGF peptide using LbL thin films to promote wound healing and decrease scar formation.
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: Anup
authors.initials: A
authors.lastname: Jose
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India.
authors.forename: Shubhmita
authors.initials: S
authors.lastname: Bhatnagar
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Janupally
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Hyderabad, 500078, Telangana, India. vamsi@hyderabad.bits-pilani.ac.in.
authors.forename: Venkata Vamsi Krishna
authors.initials: VV
authors.lastname: Venuganti
mesh_terms: D000464:Alginates / Q000737:chemistry; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003094:Collagen / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004815:Epidermal Growth Factor / Q000008:administration & dosage* / Q000737:chemistry*; D004926:Escherichia coli / Q000187:drug effects; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects; D013718:Tensile Strength / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000008:administration & dosage* / Q000737:chemistry*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D020723:Glucuronic Acid; D003094:Collagen; D048271:Chitosan
keywords: TGF-β siRNA; co-delivery; epidermal growth factor; layer-by-layer thin films; wound healing