title: In Vitro and In Vivo Sustained Zero-Order Delivery of Rapamycin (Sirolimus) From a Biodegradable Intraocular Device.
abstract: OBJECTIVE
  We created implantable intraocular devices capable of constant and continuous rapamycin release on the scale of months to years.
  
  
  METHODS
  Polycaprolactone (PCL) thin films were used to encapsulate rapamycin to create implantable and biodegradable intraocular devices. Different film devices were studied by modifying the size, thickness, and porosity of the PCL films.
  
  
  RESULTS
  In vitro release of rapamycin was observed to be constant (zero-order) through 14 weeks of study. Release rates were tunable by altering PCL film porosity and thickness. In vivo release of rapamycin was observed out through 16 weeks with concentrations in the retina-choroid in the therapeutic range. Rapamycin concentration in the blood was below the lower limit of quantification. The drug remaining in the device was chemically stable in vitro and in vivo, and was sufficient to last for upwards of 2 years of total release. The mechanism of release is related to the dissolution kinetics of crystalline rapamycin.
  
  
  CONCLUSIONS
  Microporous PCL thin film devices demonstrate good ocular compatibility and the ability to release rapamycin locally to the eye over the course of many weeks.
authors.affiliation: University of California at Berkeley-University of California, San Francisco Bioengineering Graduate Program, San Francisco, California, United States.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Lance
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Good
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Thaís S
authors.initials: TS
authors.lastname: Mendes
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Mynna
authors.initials: M
authors.lastname: Ishikiriyama
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Chew
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Estes
authors.affiliation: Pharmaceutical Development Group, Pharmaceutical Development Center, Santen Pharmaceutical Co., Ltd., Nara, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Pharmaceutical Development, Santen, Inc., Emeryville, California, United States.
authors.forename: Sri
authors.initials: S
authors.lastname: Mudumba
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Bhisitkul
authors.affiliation: University of California at Berkeley-University of California, San Francisco Bioengineering Graduate Program, San Francisco, California, United States 3Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Fra.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000869:Anterior Eye Segment; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005500:Follow-Up Studies; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D011817:Rabbits; D020123:Sirolimus / Q000008:administration & dosage*; D013997:Time Factors; D014605:Uveitis / Q000188:drug therapy*
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D020123:Sirolimus