The invention relates to methods for the preparation of a pharmaceutical-vesicle formulation comprising steps of: preparing and processing vesicle components and a pharmaceutical agent to entrap the pharmaceutical agent in the vesicle and form a pharmaceutical-vesicle formulation, wherein the pharmaceutical-vesicle formulation is reconstituted in a known quantity of the pharmaceutical agent dissolved in a pharmaceutically-acceptable carrier to provide a biphasic pharmaceutical-vesicle formulation. The invention also relates to the associated pharmaceutical-vesicle formulations, pharmaceutical kits and uses as a medicament, in particular for the prevention or treatment of infection by bacteria such as Burkholderia pseudomallei and Francisella tularensis, and viruses such as Venezuelan Equine Encephalitis Virus (VEEV).

The present invention discloses a drug delivery system for targeted therapy comprising a functionalized lipid-based nanoplatform, where at least one ligand is coupled to the surface of the nanoplatform and encapsulates at least one pharmaceutically active ingredient. A process for obtaining the drug delivery system of the present invention is also disclosed as well as a composition comprising the system of the invention. The invention relates to the field of medicine and biotechnology. The present solution aims at developing targeting co-encapsulating nanostructured lipid carriers for the treatment of different types of cancer, including glioblastoma, as well as other diseases and disorders, envisioning the establishment of an in vitro/in vivo correlation.

Provided are methods for treating a disease, disorder, or condition associated with an acid ceramidase (AC) biological activity. The methods include administering to a subject in need thereof a composition including an AC inhibitor and at least one additional active agent, such as a C6-ceramide nanoliposome (CNL); an inhibitor of a Bcl-2 family protein; a hypomethylating agent; an intensive chemotherapeutic agent such as cytarabine (AraC) and/or daunorubicin; a Hedgehog pathway inhibitor; a targeted agent, such as a FLT2 inhibitor or a EDH1/2 inhibitor; and/or an antibody drug conjugate that targets, for example, CD-33. The composition can include N-[(2S,3R)-1,3-dihydroxyoctadecan-2-yl]2-chloroacetamide (SACLAC) or a pharmaceutically acceptable salt thereof and at least one additional active agent. The disease, disorder, or condition associated with the AC biological activity can be a cancer, such as acute myeloid leukemia (AML).

The present disclosure describes compounds of Formula (I) or a pharmaceutically acceptable salt thereof:

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wherein: R.sup.1 and R.sup.2 are each independently (CH.sub.3(CH.sub.2).sub.m).sub.2CH—, (CH.sub.3(CH.sub.2).sub.m)(CH.sub.3(CH.sub.2).sub.m-1)CH, (CH.sub.3(CH.sub.2).sub.m)(CH.sub.3(CH.sub.2).sub.m-2)CH, (CH.sub.3(CH.sub.2).sub.m).sub.2CHCH.sub.2—, or (CH.sub.3(CH.sub.2).sub.m)(CH.sub.3(CH.sub.2).sub.m-1)CHCH.sub.2—, wherein m is 4-11; L.sup.1 and L.sup.2 are each independently absent, a linear C.sub.1-5 alkylene, or (CH.sub.2).sub.p—O—(CH.sub.2).sub.q, wherein p and q are each independently 1-3; R.sup.3 is a linear C.sub.2-5 alkylene optionally substituted with one or two methyl groups; R.sup.4 and R.sup.5 are each independently H or C.sub.1-6 alkyl; X is O or S; and n is 0-2.

A lipid membrane structure includes, as lipid components, a lipid compound represented by Formula (I):
(R.sup.1)(R.sup.2)C(OH)—(CH.sub.3).sub.a—(O—CO).sub.b—X  (I) [in the formula, a represents an integer of 3 to 5; b represents an integer of 0 or 1; R.sup.1 and R.sup.2 each independently represents a linear hydrocarbon group that may have —CO—O—; and X represents a 5- to 7-membered non-aromatic heterocyclic group or a group represented by Formula (B) (in the formula, d represents an integer of 0 to 3, and R.sup.3 and R.sup.4 each independently represents a C.sub.1-4 alkyl group or a C.sub.2-4 alkenyl group, where, R.sup.3 and R.sup.4 may be bonded to each other to form a 5- to 7-membered non-aromatic heterocycle (where, one or two C.sub.1-4 alkyl groups or C.sub.2-4 alkenyl groups may be substituted on the ring)].

The present invention relates to lipid nanoparticles (LNP) or compositions thereof for delivery of mRNA molecules encoding CAR, nucleic acid molecule, and/or therapeutic agents to selected targets, such as cells. Thus, in various aspects, the present invention also provides methods of preventing or treating diseases or disorders in a subject in need thereof using the said LNPs or compositions thereof.

The present invention provides compositions comprising phase separated nanoparticles, as well as methods of making the nanoparticles and uses thereof. The nanoparticles can be conjugated to therapeutics and used to treat diseases or to screen compounds.

The present invention relates to a formulation comprising blends of formulations (or colloidal dispersions) and its topical application. The formulation comprises at least two different types of colloidal dispersion comprising deformable colloidal particles, wherein the deformable colloidal particles comprise a non-ionic surfactant and/or a phospholipid. The deformable colloidal particles of the invention may comprise an agent of interest (AOI) or may be free of an AOI. The formulation may comprise an AOI that is not associated with the deformable colloidal particles. The present invention also includes kits comprising the formulation of the present invention and the use of the formulation in medicine, skin care and cosmetics.

The present invention relates to a cationic lipid having one or more biodegradable groups located in a lipidic moiety (e.g., a hydrophobic chain) of the cationic lipid. These cationic lipids may be incorporated into a lipid particle for delivering an active agent, such as a nucleic acid. The invention also relates to lipid particles comprising a neutral lipid, a lipid capable of reducing aggregation, a cationic lipid of the present invention, and optionally, a sterol. The lipid particle may further include a therapeutic agent such as a nucleic acid.

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This disclosure relates to mRNA therapy for the treatment of methylmalonic acidemia (MMA). mRNAs for use in the invention, when administered in vivo, encode methylmalonyl-CoA mutase (MUT). mRNA therapies of the disclosure increase and/or restore deficient levels of MUT expression and/or activity in subjects.