title: Treatment of otitis media by transtympanic delivery of antibiotics.
abstract: Otitis media is the most common reason U.S. children receive antibiotics. The requisite 7- to 10-day course of oral antibiotics can be challenging to deliver in children, entails potential systemic toxicity, and encourages selection of antimicrobial-resistant bacteria. We developed a drug delivery system that, when applied once to the tympanic membrane through the external auditory canal, delivers an entire course of antimicrobial therapy to the middle ear. A pentablock copolymer poloxamer 407-polybutylphosphoester (P407-PBP) was designed to flow easily during application and then to form a mechanically strong hydrogel on the tympanic membrane. U.S. Food and Drug Administration-approved chemical permeation enhancers within the hydrogel assisted flux of the antibiotic ciprofloxacin across the membrane. This drug delivery system completely eradicated otitis media from nontypable Haemophilus influenzae (NTHi) in 10 of 10 chinchillas, whereas only 62.5% of animals receiving 1% ciprofloxacin alone had cleared the infection by day 7. The hydrogel system was biocompatible in the ear, and ciprofloxacin was undetectable systemically (in blood), confirming local drug delivery and activity. This fast-gelling hydrogel could improve compliance, minimize side effects, and prevent systemic distribution of antibiotics in one of the most common pediatric illnesses, possibly minimizing the development of antibiotic resistance.
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.affiliation: Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Sabharwal
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Obiajulu S
authors.initials: OS
authors.lastname: Okonkwo
authors.affiliation: Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Nadya
authors.initials: N
authors.lastname: Shlykova
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Rong
authors.initials: R
authors.lastname: Tong
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Lily Yun
authors.initials: LY
authors.lastname: Lin
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shutao
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Otology and Laryngology, Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Rosowski
authors.affiliation: Division of Pediatric Infectious Diseases, Maxwell Finland Laboratory for Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
authors.affiliation: Laboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. daniel.kohane@childrens.harvard.edu.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Kohane
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001672:Biocompatible Materials / Q000737:chemistry; D001696:Biomechanical Phenomena; D002648:Child; D002682:Chinchilla; D002939:Ciprofloxacin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006192:Haemophilus Infections; D006193:Haemophilus influenzae; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D008297:Male; D008422:Materials Testing; D010033:Otitis Media / Q000188:drug therapy*; D020442:Poloxamer / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry; D057170:Translational Research, Biomedical; D014432:Tympanic Membrane
chemical_list: D000900:Anti-Bacterial Agents; D001672:Biocompatible Materials; D020100:Hydrogels; D011091:Polyesters; D020442:Poloxamer; D002939:Ciprofloxacin