Methods and biocompatible compositions to achieve sustained drug release in the eye
Inventors
Barman, Shikha P. • Liu, Moli • Barman, Koushik • Ward, Kevin L. • Hackett, Brendan
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Assignees
Member
Integral BioSystems, LLCIntegral BioSystems is a pharmaceutical contract research organization working on complex products such as long-acting injectables, suspensions, injectables and topical formulations for intranasal, dermal, ophthalmic, subQ and intramuscular routes. It provides preclinical formulation, analytical, testing, and process-development services for complex drug products, including small molecules, proteins, peptides, and nucleic acids. Its work spans route-specific dosage-form development, cGLP studies, stability and release testing, scale-up, and technology transfer. The company has an innovation-focused wholly owned subsidiary, Symphony Therapeutics, LLC, with licensable products (OcuHeal-UV400+, NanoM-Wafer Lubricating Bandage). Symphony is operating within Integral facilities.
Integral BioSystems is a pharmaceutical contract research organization working on complex products such as long-acting injectables, suspensions, injectables and topical formulations for intranasal, dermal, ophthalmic, subQ and intramuscular routes. It provides preclinical formulation, analytical, testing, and process-development services for complex drug products, including small molecules, proteins, peptides, and nucleic acids. Its work spans route-specific dosage-form development, cGLP studies, stability and release testing, scale-up, and technology transfer. The company has an innovation-focused wholly owned subsidiary, Symphony Therapeutics, LLC, with licensable products (OcuHeal-UV400+, NanoM-Wafer Lubricating Bandage). Symphony is operating within Integral facilities.
Publication Number
US-9931306-B2
Publication Date
2018-04-03
Expiration Date
Abstract
A nanostructured biocompatible wafer for placement in the conjunctival cul-de-sac. The wafer contains a tissue-reactive mucoadhesive polymer and a mesh formed of a plurality of hydrophobic polymer fibers. Also provided is a method for treating glaucoma, an ocular surface disorder, or an ocular surface infection using the nanostructured biocompatible wafer. Additionally, an injectable sustained-release formulation for treating an ocular disorder is disclosed. The formulation includes a drug contained within a plurality of microparticles formed of a biodegradable polymer and are coated with a tissue-reactive compound. Further provided is a method for treating an ocular disorder by injecting the microparticulate sustained release formulation.
Core Innovation
The invention provides a nanostructured biocompatible wafer for placement in the conjunctival cul-de-sac. The wafer comprises a tissue-reactive mucoadhesive polymer and a mesh formed of a plurality of polymer fibers, with the tissue-reactive mucoadhesive polymer being coated on the wafer or intercalated with the fibers. The wafer is defined by structural constraints including thickness of 0.05 mm to 0.5 mm, a hydrated flexural modulus less than 25 MPa, and an oxygen permeability of 15 Dk to 30 Dk.
The mesh geometry is defined by a pore size of 50 nm to 1000 nm, and polymer fiber diameter of 100 nm to 1500 nm. This nanostructured mesh and polymer arrangement is presented as a conjunctival sustained-release ocular approach intended to address limitations of conventional eye-drop dosing. The description emphasizes hydration and mucoadhesion behavior associated with the tissue-reactive mucoadhesive polymer and the nanostructured polymer-fiber mesh.
In addition to the wafer, the disclosed content includes an injectable sustained-release formulation comprising drug-loaded biodegradable polymer microparticles with a tissue-reactive coating. The disclosure further includes multi-drug and layered delivery architectures in the ocular system, including multi-layer and coaxial or tri-axial fiber architectures with drug-containing inner and outer layers. The therapeutic use described includes glaucoma therapy and ocular surface disorders and infections, supported by example drug embodiments such as travoprost, brinzolamide, latanoprost, loteprednol etabonate, and tobramycin.
Claims Coverage
The document provides one independent claim directed to a nanostructured biocompatible conjunctival wafer and describes multiple structural and delivery refinements through dependent claims. The inventive features across the claim set focus on the polymer-fiber mesh geometry and performance ranges, the tissue-reactive mucoadhesive polymer configuration, and drug-loading architectures and ocular treatment use constraints.
Conjunctival nanostructured biocompatible wafer with tissue-reactive mucoadhesive polymer and polymer-fiber mesh
A nanostructured biocompatible wafer for placement in the conjunctival cul-de-sac, comprising a tissue-reactive mucoadhesive polymer and a mesh formed of a plurality of polymer fibers, wherein the tissue-reactive mucoadhesive polymer is coated on the wafer or intercalated with the fibers.
Performance-constrained wafer thickness, hydrated flexural modulus, and oxygen permeability
The wafer has a thickness of 0.05 mm to 0.5 mm, a hydrated flexural modulus less than 25 MPa, and an oxygen permeability of 15 Dk to 30 Dk.
Mesh pore size and fiber diameter geometry
The mesh has a pore size of 50 nm to 1000 nm; and the polymer fibers have a diameter of 100 nm to 1500 nm.
Tissue-reactive mucoadhesive polymer selection
The tissue-reactive mucoadhesive polymer is selected from PEG-succinimidyl glutarate, PEG-amine, polylysine, xanthan gum, or hyaluronic acid.
Biocompatible polymer fiber selection
The polymer fibers are chosen from polylactide-co-glycolide, polylactic acid, polycaprolactone, poly(trimethylene carbonate), poly(amino acids), hyaluronic acid, polyethylene glycol (PEG), polyethylene oxide-polypropylene oxide-polyethylene oxide tri-block copolymer, PEG-stearate, PEG-distearoyl-glycero-3-phosphoethanolamine, lecithin, xanthan, polyvinylalcohol, polyvinylpyrrolidone, or a combination thereof.
Drug identity in the wafer as a first drug selection
The first drug is selected from travoprost, brinzolamide, latanoprost, unoprostone, bimatoprost, timolol, or combinations thereof.
Two-drug coaxial polymer fiber architecture with inner and outer layer placement
The nanostructured biocompatible wafer includes two different drugs delivered from coaxial polymer fibers, with one drug in an inner polymer layer and the other drug in an outer polymer layer.
Method of treating an ocular surface infection by maintaining the wafer in the conjunctival cul-de-sac
A method treats an ocular surface infection by identifying a subject needing treatment, placing a nanostructured biocompatible wafer into the subject’s conjunctival cul-de-sac, and maintaining it there for 1 to 2 months.
Overall, the claim coverage centers on a conjunctival wafer defined by specific mucoadhesive polymer placement, mesh geometry, and performance constraints. Dependent claim refinements specify tissue-reactive mucoadhesive polymer and polymer fiber options, define drug identity selections, and describe layered coaxial architectures for delivering two drugs with inner and outer layer placement, as well as an ocular surface infection treatment use constraint.
Stated Advantages
Provides sustained-release ocular functionality intended to address limitations of conventional eye-drop dosing.
Emphasizes biocompatibility/irritation screening correlations with thickness/modulus/oxygen permeability.
Supports multi-drug delivery using layered coaxial architectures.
Documented Applications
Glaucoma therapy.
Ocular surface disorders.
Ocular surface infections.
Post-cataract inflammation treatment using loteprednol etabonate.
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