title: Evaluation of Intracameral Pentablock Copolymer Thermosensitive Gel for Sustained Drug Delivery to the Anterior Chamber of the Eye.
abstract: To investigate PTSgels (Pentablock copolymers) as an injectable formulation technology for sustained ocular drug delivery. Drug release profile, tolerability, and polymer degradation for one of the thermosensitive, biodegradable, and biocompatible compositions were investigated through intracameral (IC) injection in rabbits.
  
  
  
  New Zealand White rabbit eyes were injected IC (50 μL) with 100 μg near-infrared-immunoglobulin G (NIR-IgG) in balanced salt solution (BSS) or 20% PTSgel; or with PTSgel or BSS alone. Ocular irritation scoring, intraocular pressure (IOP), and corneal thickness (CT) measurement, as well as color and infrared photography, were performed for up to 28 days postinjection. Upon euthanasia at 7, 14, or 28 days, eyes underwent ex vivo imaging (Xenogen IVIS) followed by tissue fixation and histopathology.
  
  
  
  IC injection of PTSgel (liquid at room temperature) was performed without difficulty using a 31G needle. The polymer quickly gelled in the IC space resulting in an inferior anterior chamber deposit. The tested PTSgel was well tolerated, with no significant changes in IOP or CT. Eyes injected with NIR-IgG in PTSgel had visible NIR-IgG through 9 days postinjection, and ex vivo imaging detected a strong NIR-IgG signal in the anterior chamber through day 28. The gel deposit steadily decreased in size over time and was nearly eliminated by 28 days.
  
  
  
  The PTSgel released IgG for 28 days and was well tolerated. The polymer degraded in parallel with drug release. These results demonstrate the potential of intracameral PTSgel formulations for sustained delivery of biologic therapies to the ocular anterior segment.
authors.affiliation: 1 Laboratory of Ocular Toxicology, Immunology, and Drug Delivery, North Carolina State University , Raleigh, North Carolina.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schaefer
authors.affiliation: 1 Laboratory of Ocular Toxicology, Immunology, and Drug Delivery, North Carolina State University , Raleigh, North Carolina.
authors.forename: Sara M
authors.initials: SM
authors.lastname: Smith
authors.affiliation: 1 Laboratory of Ocular Toxicology, Immunology, and Drug Delivery, North Carolina State University , Raleigh, North Carolina.
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Salmon
authors.affiliation: 2 Symmetry Biosciences , Research Triangle Park, North Carolina.
authors.forename: Santhi
authors.initials: S
authors.lastname: Abbaraju
authors.affiliation: 2 Symmetry Biosciences , Research Triangle Park, North Carolina.
authors.forename: Rasidul
authors.initials: R
authors.lastname: Amin
authors.affiliation: 3 i-novion, Inc. , Randolph, New Jersey.
authors.forename: Sidney
authors.initials: S
authors.lastname: Weiss
authors.affiliation: 3 i-novion, Inc. , Randolph, New Jersey.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Grau
authors.affiliation: 3 i-novion, Inc. , Randolph, New Jersey.
authors.forename: Poonam
authors.initials: P
authors.lastname: Velagaleti
authors.affiliation: 1 Laboratory of Ocular Toxicology, Immunology, and Drug Delivery, North Carolina State University , Raleigh, North Carolina.|3 i-novion, Inc. , Randolph, New Jersey.
authors.forename: Brian
authors.initials: B
authors.lastname: Gilger
mesh_terms: D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects / Q000378:metabolism*; D016503:Drug Delivery Systems; D004361:Drug Tolerance; D005782:Gels / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D056965:Injections, Intraocular; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011817:Rabbits; D013696:Temperature
chemical_list: D005782:Gels; D011108:Polymers
keywords: copolymer; intracameral; ocular; pentablock; sustained drug delivery