title: Biocompatibility and Pharmacokinetic Analysis of an Intracameral Polycaprolactone Drug Delivery Implant for Glaucoma.
abstract: We developed polycaprolactone (PCL) implants that achieve zero-order release of a proprietary ocular hypotensive agent (DE-117) over 6 months.
  
  
  
  The release rates of DE-117-loaded PCL devices were tuned based on an established predictive model and confirmed by in vitro release studies. Devices containing DE-117 and empty devices were implanted intracamerally in normotensive rabbits for up to 8 weeks' duration. Devices were retrieved after rabbits were euthanized and evaluated for tissue adherence. The drug remaining in each device was analyzed by high performance liquid chromatography. Drug distribution in ocular tissues was measured by liquid chromatography coupled with a tandem mass spectrometry (LC/MS/MS).
  
  
  
  In vitro release of DE-117 showed zero-order release with a release rate of 0.5 μg/day over 6 months. Implantation in rabbit eyes demonstrated that the devices were well tolerated in the intracameral space. Quantification of DE-117 and hDE-117 (the hydrolyzed active form of DE-117) in ocular tissues (cornea, iris-ciliary body, aqueous humor, and vitreous humor) indicated sustained release of DE-117 and its conversion to hDE-117 when released from the device. Analysis of drug remaining in the device found that concentration of hDE-117 was below the limit of detection, indicating the encapsulated drug was protected from hydrolysis in the device.
  
  
  
  Proof-of-concept PCL drug delivery devices containing DE-117 show promise as a long-term glaucoma treatment based on their zero-order drug release profile in vitro, biocompatibility in vivo, and effective distribution of released drug in relevant ocular tissues.
authors.affiliation: UCB-UCSF Graduate Program in Bioengineering, San Francisco, California, United States.
authors.forename: Jean
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Max
authors.initials: M
authors.lastname: Kudisch
authors.affiliation: Santen, Inc., Emeryville, California, United States.
authors.forename: Sri
authors.initials: S
authors.lastname: Mudumba
authors.affiliation: Santen Pharmaceutical Co., Ltd., Nara RD Center, Nara, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Asada
authors.affiliation: Santen Pharmaceutical Co., Ltd., Nara RD Center, Nara, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Aya-Shibuya
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: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, United States.
authors.forename: Tejal A
authors.initials: TA
authors.lastname: Desai
mesh_terms: D000818:Animals; D000867:Anterior Chamber; D001082:Aqueous Humor / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D016503:Drug Delivery Systems; D004343:Drug Implants; D005500:Follow-Up Studies; D005901:Glaucoma / Q000188:drug therapy* / Q000378:metabolism; D008422:Materials Testing / Q000379:methods*; D011091:Polyesters; D011455:Prostaglandins A, Synthetic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits; D053719:Tandem Mass Spectrometry
chemical_list: D004343:Drug Implants; D011091:Polyesters; D011455:Prostaglandins A, Synthetic; C016240:polycaprolactone