title: Antibiotic-free nanotherapeutics: hypericin nanoparticles thereof for improved in vitro and in vivo antimicrobial photodynamic therapy and wound healing.
abstract: Hypericin (HY) is a naturally-occurring, potent photosensitizer. However, its lipophilicity limits its therapeutic applications. Our attempt is, thus, to develop a biodegradable nanocarrier for hypericin capable of preserving its antibacterial photoactivity. Amphiphilic block copolymers were synthesized to prepare hypericin-laden nanoparticles (HY-NPs). The antimicrobial photoactivity of HY-NPs was assessed; in vitro against biofilm and planktonic cells of methicillin resistant Staphylococcus aureus (MRSA) clinical isolates and in vivo on infected wounds in rats. Nanoparticles of 45 nm in diameter ensured higher amounts of reactive oxygen species upon irradiation. HY-NPs demonstrated superior inhibition of biofilm over planktonic cells. In vivo wound healing studies in rats revealed faster healing, better epithelialization, keratinization and development of collagen fibers when HY-NPs were applied. Determination of growth factors and inflammatory mediators in the wound area confirmed superior healing potential of nanoencapsulated hypericin suggesting that hypericin can join the era of antibiotic-free antimicrobial therapy.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt. noha.nafee@mx.uni-saarland.de
authors.forename: Noha
authors.initials: N
authors.lastname: Nafee
authors.forename: Alaa
authors.initials: A
authors.lastname: Youssef
authors.forename: Hanan
authors.initials: H
authors.lastname: El-Gowelli
authors.forename: Heba
authors.initials: H
authors.lastname: Asem
authors.forename: Sherif
authors.initials: S
authors.lastname: Kandil
mesh_terms: D000818:Animals; D000873:Anthracenes; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D050997:Nanomedicine; D053758:Nanoparticles; D010316:Particle Size; D010569:Perylene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*; D014946:Wound Infection / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology
chemical_list: D000873:Anthracenes; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D017319:Photosensitizing Agents; D011091:Polyesters; D017382:Reactive Oxygen Species; C016240:polycaprolactone; D011092:Polyethylene Glycols; D010569:Perylene; C004965:hypericin
keywords: Amphiphilic copolymers; HY; Hypericin; MRSA; MRSA biofilms; NPs; Nanoparticles; PCL; PEG; PS; Photodynamic therapy; aPDT; antimicrobial photodynamic therapy; hypericin; methicillin-resistant Staphyllococcus aureus; nanoparticles; photosensitizer; polycaprolactone; polyethylene glycol