Combination HIV therapeutic
Inventors
Assignees
Publication Number
US-11234932-B2
Publication Date
2022-02-01
Expiration Date
2037-11-21
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Abstract
Embodiments of the present invention are directed to particles having a Bryoid and a HDAC inhibitor for the treatment of latent viral disease.
Core Innovation
The invention is directed to particles, compositions, medicaments, and methods for treating latent viral diseases, particularly latent HIV infection. The invention features a combination of a Bryoid, such as Bryostatin, and a Histone Deacetylase (HDAC) inhibitor within a specially structured particle. The particles have a core composed of a hydrophilic material mixed with an HDAC inhibitor, surrounded by a hydrophobic material mixed with a Bryoid, and are provided with an outer surface that can be functionalized with ligands.
The primary problem being addressed is the inability of existing antiretroviral therapy (ART) to eradicate latent HIV-infected cellular reservoirs, which persist as a source of viral reactivation. Current ART cannot effectively target these latent reservoirs, and even potent agents like HDAC inhibitors alone have failed to clear HIV-1 reservoirs. Additional strategies are required because intensification of ART has not proved effective and persistent reservoirs remain a significant hurdle to virus eradication.
This invention uniquely proposes the co-encapsulation of both a Bryoid and an HDAC inhibitor in nanoparticles, enabling simultaneous delivery and targeting to latent viral reservoirs. The surface of these particles can be modified with antibodies or ligands specific to viral components or for upregulation of CD4 cells to enhance therapeutic targeting. The patent describes processes for manufacturing such particles, including the use of supercritical, critical, or near-critical fluids for efficient encapsulation of the therapeutic agents.
Claims Coverage
There are two independent claims in the patent, each addressing a core inventive feature relating to the formulation and process for making nanosomes for the treatment of latent viral diseases.
Formulation of nanosome with specific core-shell structure encapsulating HDAC inhibitor and Bryoid
The invention involves making a nanosome for treatment of latent viral diseases, comprising: - An aqueous core containing a mixture of a hydrophilic material and an HDAC inhibitor. - A surrounding layer containing a mixture of a phospholipid and a Bryoid. - An outer surface encapsulating the nanosome.
Process for manufacturing nanosome using supercritical, critical, or near-critical fluid techniques to encapsulate therapeutics
The invention provides a method comprising: 1. Providing phospholipid material in supercritical, critical or near critical fluid. 2. Providing a Bryoid in an alcohol solution. 3. Forming a mixture of the phospholipid fluid and the Bryoid solution in an inline mixer. 4. Decompressing the mixture using a backpressure regulator. 5. Injecting the mixture as a stream through an injection nozzle into a decompression vessel containing an HDAC inhibitor in a hydrophilic aqueous solution. During this process, bubbles form at the nozzle, detach, and rupture, causing phospholipid bilayers to encapsulate the solute molecules, thereby forming nanosomes with an aqueous core containing the HDAC inhibitor and a phospholipid shell containing the Bryoid.
The claims establish a nanosome with a specific encapsulation structure for the co-delivery of a Bryoid and an HDAC inhibitor, as well as a specialized method for producing these nanosomes using supercritical fluid techniques.
Stated Advantages
The co-encapsulation of both drugs ensures simultaneous delivery to the intended target, enhancing therapeutic efficacy.
Targeting with broadly neutralizing antibodies and anti-PD-L1 nanobodies on the particle surface allows for efficient activation of HIV latency and immunological depletion of latent reservoirs.
Encapsulation in liposomes significantly reduces systemic toxicities associated with Bryostatin-1 and HDAC inhibitors.
Pegylation increases the residence time of the circulating nanoparticles, thereby increasing therapeutic efficacy and overall therapeutic index.
Therapeutic activity can be achieved at lower concentrations, minimizing activation of pathways that may result in negative side effects.
The process reduces product volatilization, oxidation, processing time, and organic solvent usage during production.
Documented Applications
Treatment of latent viral diseases, including latent HIV infection.
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