Evaluation of Intracameral Pentablock Copolymer Thermosensitive Gel for Sustained Drug Delivery to the Anterior Chamber of the Eye

被引:6
|
作者
Schaefer, Elizabeth [1 ]
Smith, Sara M. [1 ]
Salmon, Jacklyn [1 ]
Abbaraju, Santhi [2 ]
Amin, Rasidul [2 ]
Weiss, Sidney [3 ]
Grau, Ulrich [3 ]
Velagaleti, Poonam [3 ]
Gilger, Brian [1 ,3 ]
机构
[1] North Carolina State Univ, Lab Ocular Toxicol Immunol & Drug Delivery, 1060 William Moore Dr, Raleigh, NC 27607 USA
[2] Symmetry Biosci, Res Triangle Pk, NC USA
[3] I Novion Inc, Randolph, NJ USA
关键词
ocular; sustained drug delivery; intracameral; pentablock; copolymer; RELEASE; PLGA; DEGRADATION; PROTEINS;
D O I
10.1089/jop.2016.0181
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Purpose: 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. Methods: New Zealand White rabbit eyes were injected IC (50L) with 100g 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. Results: 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. Conclusions: 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.
引用
收藏
页码:353 / 360
页数:8
相关论文
共 50 条
  • [1] Sustained IgG delivery to the anterior chamber of rabbits using pentablock co-polymers
    Schaefer, Elizabeth
    Salmon, Jacklyn H.
    Abbaraju, Santhi
    Amin, Rasidul
    Weiss, Sidney L.
    Grau, Ulrich M.
    Velagaleti, Poonam
    Gilger, Brian C.
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2016, 57 (12)
  • [2] Evaluation of ocular biocompatibility and duration of a bioerodible intravitreal pentablock co-polymer thermosensitive gel and/or nanoparticle ocular drug delivery system
    Gilger, Brian C.
    Salmon, Jacklyn H.
    Patel, Sulabh P.
    Velagaleti, Poonam
    Weiss, Sidney L.
    Mitra, Ashim K.
    Grau, Ulrich
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2014, 55 (13)
  • [3] Formulation development and Evaluation of Thermosensitive gel for Vaginal Drug Delivery
    Bhat, Sudeendra R.
    Shivakumar, Hosakote G.
    LATIN AMERICAN JOURNAL OF PHARMACY, 2010, 29 (07): : 1093 - 1099
  • [4] Topical Delivery of Levocarnitine to the Cornea and Anterior Eye by Thermosensitive in-situ Gel for Dry Eye Disease
    Ma, Baorui
    Pang, Linnuo
    Huang, Pingqing
    Bai, Jie
    Zhang, Zhiqin
    Wu, Huimin
    Cai, Mengru
    Yang, Jin
    Xu, Yuchen
    Yin, Xingbin
    Qu, Changhai
    Ni, Jian
    DRUG DESIGN DEVELOPMENT AND THERAPY, 2021, 15 : 2357 - 2373
  • [5] Evaluation of pentablock co-polymer (PTSsol) for sustained topical ocular drug delivery
    Smith, Sara M.
    Abbaraju, Santhi
    Salmon, Jacklyn H.
    Amin, Rasidul
    Weiss, Sidney L.
    Grau, Ulrich
    Velagaleti, Poonam
    Gilger, Brian C.
    JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, 2017, 39 : 475 - 483
  • [6] Biodegradable thermosensitive copolymer hydrogels for drug delivery
    Loh, Xian Jun
    Li, Jun
    EXPERT OPINION ON THERAPEUTIC PATENTS, 2007, 17 (08) : 965 - 977
  • [7] Novel Thermosensitive Pentablock Copolymers for Sustained Delivery of Proteins in the Treatment of Posterior Segment Diseases
    Patel, Sulabh P.
    Vaishya, Ravi
    Yang, Xiaoyan
    Pal, Dhananjay
    Mitra, Ashim K.
    PROTEIN AND PEPTIDE LETTERS, 2014, 21 (11): : 1185 - 1200
  • [8] Novel Pentablock Copolymer Based Nanoformulations for Sustained Ocular Delivery of Protein Therapeutics
    Agrahari, Vibhuti
    Patel, Sulabh P.
    Mitra, Ashim K.
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2014, 55 (13)
  • [9] Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery
    Sulabh P. Patel
    Ravi Vaishya
    Dhananjay Pal
    Ashim K. Mitra
    AAPS PharmSciTech, 2015, 16 : 327 - 343
  • [10] Novel Pentablock Copolymer-Based Nanoparticulate Systems for Sustained Protein Delivery
    Patel, Sulabh P.
    Vaishya, Ravi
    Pal, Dhananjay
    Mitra, Ashim K.
    AAPS PHARMSCITECH, 2015, 16 (02): : 327 - 343