Nathan H Dormer1, Jennifer Nelson-Brantley2, Hinrich Staecker2, Cory J Berkland3. 1. Orbis Biosciences, 8006 Reeder Street, Lenexa, KS, USA. Electronic address: nate@orbisbio.com. 2. The University of Kansas Medical Center, Department of Otolaryngology-Head and Neck Surgery, 3901 Rainbow Boulevard, Kansas City, KS, USA. 3. Orbis Biosciences, 8006 Reeder Street, Lenexa, KS, USA; The University of Kansas Department of Pharmaceutical Chemistry, 2030 Becker Drive, Lawrence, KS, USA.
Abstract
OBJECTIVE: The current investigation evaluated a novel extended release delivery system for treating inner ear diseases. The platform technology consists of a film forming agent (FFA) and microsphere component to localize and extend drug delivery within the ear. STUDY DESIGN: Studies evaluated dissolution kinetics of microspheres with multiple encapsulates, testing of a variety of FFAs, and ability to localize to the round window membrane in mice in vivo. SETTING: Studies were completed at Orbis Biosciences and The University of Kansas Medical Center. SUBJECTS: In conjunction with in vitro characterization, an infrared dye-containing microsphere formulation was evaluated for round window membrane (RWM) localization and general tolerability in C57/BL6 Mus musculus for 35 days. METHODS: In vitro characterization was performed using upright diffusion cells on cellulose acetate membranes, with drug content quantified by high performance liquid chromatography. Mus musculus dosing of infrared dye-containing microspheres was performed under anesthesia with a 27 GA needle and 2.0 μL injection volume RESULTS: In vitro dissolution demonstrates the ability of the FFA with microsphere platform to release steroids, proteins, peptides, and nucleic acids for at least one month, while necroscopy shows the ability of the FFA with dye-loaded microspheres to remain localized to Mus musculus RWM for the same period of time, with favorable tolerability. CONCLUSIONS: Combining FFA and microsphere for localized drug delivery may enable cost-effective, extended release local delivery to the inner ear of new and existing small molecules, proteins, peptides, and nucleic acids.
OBJECTIVE: The current investigation evaluated a novel extended release delivery system for treating inner ear diseases. The platform technology consists of a film forming agent (FFA) and microsphere component to localize and extend drug delivery within the ear. STUDY DESIGN: Studies evaluated dissolution kinetics of microspheres with multiple encapsulates, testing of a variety of FFAs, and ability to localize to the round window membrane in mice in vivo. SETTING: Studies were completed at Orbis Biosciences and The University of Kansas Medical Center. SUBJECTS: In conjunction with in vitro characterization, an infrared dye-containing microsphere formulation was evaluated for round window membrane (RWM) localization and general tolerability in C57/BL6Mus musculus for 35 days. METHODS: In vitro characterization was performed using upright diffusion cells on cellulose acetate membranes, with drug content quantified by high performance liquid chromatography. Mus musculus dosing of infrared dye-containing microspheres was performed under anesthesia with a 27 GA needle and 2.0 μL injection volume RESULTS: In vitro dissolution demonstrates the ability of the FFA with microsphere platform to release steroids, proteins, peptides, and nucleic acids for at least one month, while necroscopy shows the ability of the FFA with dye-loaded microspheres to remain localized to Mus musculus RWM for the same period of time, with favorable tolerability. CONCLUSIONS: Combining FFA and microsphere for localized drug delivery may enable cost-effective, extended release local delivery to the inner ear of new and existing small molecules, proteins, peptides, and nucleic acids.
Authors: Cory Berkland; Matt J Kipper; Balaji Narasimhan; Kyekyoon Kevin Kim; Daniel W Pack Journal: J Control Release Date: 2004-01-08 Impact factor: 9.776
Authors: Erin E Leary Swan; Mark J Mescher; William F Sewell; Sarah L Tao; Jeffrey T Borenstein Journal: Adv Drug Deliv Rev Date: 2008-09-21 Impact factor: 15.470
Authors: Maximilian George Dindelegan; Violeta Pașcalău; Maria Suciu; Bogdan Neamțu; Maria Perde-Schrepler; Cristina Maria Blebea; Alma Aurelia Maniu; Violeta Necula; Anca Dana Buzoianu; Miuța Filip; Alexandra Csapai; Cătălin Popa Journal: Gels Date: 2022-08-01