A61K9/1275

REMOTE LOADING OF SPARINGLY WATER-SOLUBLE DRUGS INTO LIPOSOMES
20190110991 · 2019-04-18 ·

The present invention provides liposome compositions containing sparingly soluble drugs that are used to treat life-threatening diseases. A preferred method of encapsulating a drug inside a liposome is by remote or active loading. Remote loading of a drug into liposomes containing a transmembrane electrochemical gradient is initiated by co-mixing a liposome suspension with a solution of drug, whereby the neutral form of the compound freely enters the liposome and becomes electrostatically charged thereby preventing the reverse transfer out of the liposome. There is a continuous build-up of compound within the liposome interior until the electrochemical gradient is dissipated or all the drug is encapsulated in the liposome. However, this process as described in the literature has been limited to drugs that are freely soluble in aqueous solution or solubilized as a water-soluble complex. This invention describes compositions and methods for remote loading drugs with low water solubility (<2 mg/mL). In the preferred embodiment the drug in the solubilizing agent is mixed with the liposomes in aqueous suspension so that the concentration of solubilizing agent is lowered to below its capacity to completely solubilize the drug. This results in the drug precipitating but remote loading capability is retained. The process is scalable and, in liposomes in which the lipid composition and remote loading agent are optimized, the resulting drug-loaded liposomes are characterized by a high drug-to-lipid ratios and prolonged drug retention when the liposome encapsulated drug is administered to a subject.

LIPOPROTEINS CONTAINING PLATINUM COMPLEXES FOR THE TREATMENT OF CANCER

The present invention relates to lipoproteins containing platinum complex. The invention also relates to a kit comprising said lipoproteins. In particular, the present invention relates to the use of said platinum-complex-bearing lipoproteins for the specific targeting of macrophages and tumour cells in the treatment of cancer.

BIODEGRADABLE COMPOUND, LIPID PARTICLE, COMPOSITION CONTAINING LIPID PARTICLE, AND KIT

The compound according to the present embodiment is represented by the following formula (1):


Q-LCHR.sub.2 (1)

(wherein, Q is a non-cationic aliphatic group that does not contain nitrogen but contains oxy; L is a single bond or an aliphatic group containing no nitrogen; Rs are C.sub.12-C.sub.24 aliphatic group, the same or different; and at least one R contains, in the main chain or side chain thereof, a linking group L.sup.R selected from the group consisting of C(O)O, OC(O), OC(O)O, SC(O), C(O)S, C(O)NH, and NHC(O)).

APO-E MODIFIED LIPID NANOPARTICLES FOR DRUG DELIVERY TO TARGETED TISSUES AND THERAPEUTIC METHODS

Lipid nanoparticles and methods of making and using the same, including pharmaceutical compositions and kits, and the targeted delivery of drugs in various treatment methods. The nanoparticle formulation includes phospholipids, triglycerides, cholesterol, cholesteryl ester, apolipoprotein E3 (ApoE3), and a lipophilic therapeutic agent.

DETECTION APPARATUS FOR DIFFERENTIAL-CHARGED PARTICLE MOBILITY ANALYZER
20190025317 · 2019-01-24 ·

The present invention provides devices and methods for identification and/or quantitation of particles through detection of fluorescence labeled particles in an apparatus for differential charged particle mobility analysis and fluorescence detection.

Engineered Exosomes for the Delivery of Bioactive Cargo Using Transmembrane VSV-G
20190015333 · 2019-01-17 ·

Vesicular stomatitis virus glycoprotein (VSVG) can both load protein cargo onto exosomes and increase their delivery ability via a pseudotyping mechanism. By fusing a set of fluorescent and luminescent reporters with VSVG, we show the successful targeting and incorporation of VSVG fusions into exosomes by gene transfection and fluorescence tracking. VSVG pseudotyping of exosomes does not affect the size or distributions of the exosomes, and both the full-length VSVG and the VSVG without the ectodomain integrate into the exosomal membrane, suggesting that the ectodomain is not required for protein loading. Finally, exosomes pseudotyped with full-length VSVG are internalized by multiple-recipient cell types to a greater degree compared to exosomes loaded with VSVG without the ectodomain, confirming a role of the ectodomain in cell tropism. This invention provides a new genetically encoded pseudotyping platform to load and enhance the intracellular delivery of therapeutic proteins via exosome-based vehicles to target cells.

DRIED COMPOSITION

Described herein is the formulation of immunogenic or vaccine compositions comprising neutral lipid liposome based adjuvants, where the composition is suitable for lyophilisation. In particular, the invention relates to lyophilised forms of such immunogenic or vaccine compositions wherein both the immunogen or vaccine antigen and the adjuvant are present in one and the same vial, as well as to the formulation and manufacture of lyophilised forms of such immunogenic or vaccine composition.

Lipid nanoparticles containing silyl lipids for use in vaccines and gene therapy

This disclosure provides silyl lipid molecules in which one or more carbon-to-carbon double bonds in the lipophilic portion is substituted with a silicon atom. Guidance is provided by which the reader may make silyl lipid molecules from molecular building blocks, and then incorporate silyl lipid molecules into lipid nanoparticles (LNPs). The silyl LNPs can be used as carriers of pharmaceutical agents. Flexible steric and substitution patterns of silyl groups in the LNPs give the user a way to fine-tune physicochemical properties, achieving improved stability and clinical efficacy. This technology is useful for immunization or genetic therapy, such as the preparation and administration of RNA vaccines for protection against the virus that causes COVID-19.

Silyl lipids suitable for enhanced delivery of anti-viral therapeutics

This disclosure provides silyl lipid molecules in which one or more carbon-to-carbon double bonds in the lipophilic portion is substituted with a silicon atom. Guidance is provided by which the reader may make silyl lipid molecules from molecular building blocks, and then incorporate silyl lipid molecules into lipid nanoparticles (LNPs). The silyl LNPs can be used as carriers of pharmaceutical agents. Flexible steric and substitution patterns of silyl groups in the LNPs give the user a way to fine-tune physicochemical properties, achieving improved stability and clinical efficacy. This technology is useful for immunization or genetic therapy, such as the preparation and administration of RNA vaccines for protection against the virus that causes COVID-19.

Methods and Apparatus for Creating Particle Derivatives of HDL with Reduced Lipid Content

The present invention is directed to systems, apparatus and methods for creating derivatives of at least one form of HDL without substantially affecting LDL. These derivatives of HDL are particles with reduced lipid content, particularly reduced cholesterol content. These particles have the capacity to bind cholesterol and are administered to a patient to enhance cellular cholesterol efflux and reduce cholesterol levels in cells, tissues, organs, and blood vessels. The present method is useful for treating atherogenic vascular disease and may be combined with other therapies such as statins, inhibitors of cholesterol absorption, niacin, anti-inflammatories, exercise and dietary restriction.