title: In vivo and in vitro sustained release of ranibizumab from a nanoporous thin-film device.
abstract: Current administration of ranibizumab and other therapeutic macromolecules to the vitreous and retina carries ocular risks, a high patient treatment burden, and compliance barriers that can lead to suboptimal treatment. Here we introduce a device that produces sustained release of ranibizumab in the vitreous cavity over the course of several months. Composed of twin nanoporous polymer thin films surrounding a ranibizumab reservoir, these devices provide release of ranibizumab over 16 weeks in vitro and 12 weeks in vivo, without exhausting the initial drug payload. Following implantation in vivo, devices were well-tolerated and showed no sign of immune response. This platform presents a potential solution to the challenge of delivering protein therapeutics to the vitreous and retina for sustained periods of time.
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA, 94158, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Lance
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94158, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Bernards
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94158, USA.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Ciaccio
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Good
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Thaís S
authors.initials: TS
authors.lastname: Mendes
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Kudisch
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Elliot
authors.initials: E
authors.lastname: Chan
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Mynna
authors.initials: M
authors.lastname: Ishikiriyama
authors.affiliation: Department of Ophthalmology, University of California San Francisco, 400 Parnassus Ave, 7th Floor, San Francisco, CA, 94143, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Bhisitkul
authors.affiliation: UC Berkeley - UCSF Graduate Group in Bioengineering, 1700 4th Street, QB3 Byers Hall, Room 203, San Francisco, CA, 94158, USA. tejal.desai@ucsf.edu.|Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, 94158, USA. tejal.desai@ucsf.edu.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D058608:Nanopores / Q000648:ultrastructure; D011091:Polyesters; D011817:Rabbits; D000069579:Ranibizumab / Q000008:administration & dosage* / Q000737:chemistry; D014822:Vitreous Body / Q000378:metabolism*
chemical_list: D020533:Angiogenesis Inhibitors; D003692:Delayed-Action Preparations; D011091:Polyesters; C016240:polycaprolactone; D016650:Fluorescein-5-isothiocyanate; D000069579:Ranibizumab
keywords: Biodegradable; Controlled release; Drug delivery; Nanoporous; Ranibizumab; Sustained release