The present invention relates to pre-formulations comprising low viscosity, non-liquid crystalline, mixtures of: a) at least one neutral diacyl lipid and/or at least one tocopherol; b) at least one phospholipid; c) at least one biocompatible, oxygen containing, low viscosity organic solvent;
wherein at least one bioactive agent is dissolved or dispersed in the low viscosity mixture and wherein the pre-formulation forms, or is capable of forming, at least one liquid crystalline phase structure upon contact with an aqueous fluid. The preformulations are suitable for generating parenteral, non-parenteral and topical depot compositions for sustained release of active agents. The invention additionally relates to a method of delivery of an active agent comprising administration of a preformulation of the invention, a method of treatment comprising administration of a preformulation of the invention and the use of a preformulation of the invention in a method for the manufacture of a medicament.

Disclosed are compounds of Formula 1,

##STR00001##

stereoisomers thereof, and pharmaceutically acceptable salts thereof, wherein L, r, s, R.sup.5, R.sup.6, R.sup.7, R.sup.9, R.sup.10, R.sup.11, R.sup.12, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.13, and X.sup.14 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with SSTR4.

Disclosed are compounds of Formula 1,

##STR00001##

stereoisomers thereof, and pharmaceutically acceptable salts thereof, wherein L, r, s, R.sup.5, R.sup.6, R.sup.7, R.sup.9, R.sup.10, R.sup.11, R.sup.12, X.sup.1, X.sup.2, X.sup.3, X.sup.4, X.sup.13, and X.sup.14 are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with SSTR4.

Treatments for cancer include miriplatin assembled into an ultra-small dot (uPtD) and/or lomitapide or a pharmaceutically-acceptable salt thereof. The uPtD and/or lomitapide can be encapsulated in a nanoparticle for administration to a subject. Some embodiments further include paclitaxel or a pharmaceutically-acceptable salt thereof.

Treatments for cancer include miriplatin assembled into an ultra-small dot (uPtD) and/or lomitapide or a pharmaceutically-acceptable salt thereof. The uPtD and/or lomitapide can be encapsulated in a nanoparticle for administration to a subject. Some embodiments further include paclitaxel or a pharmaceutically-acceptable salt thereof.

Treatments for cancer include miriplatin assembled into an ultra-small dot (uPtD) and/or lomitapide or a pharmaceutically-acceptable salt thereof. The uPtD and/or lomitapide can be encapsulated in a nanoparticle for administration to a subject. Some embodiments further include paclitaxel or a pharmaceutically-acceptable salt thereof.

Treating, and compositions for treating, a condition and/or a symptom associated with an effect of at least one element of the opioid system in an animal by administering to the animal (i) a therapeutically effective amount of at least one microorganism and/or of a prebiotic thereof, where the microorganism is capable of modulating an effect of at least one element of the opioid system of the animal and (ii) a therapeutically effective amount of at least one compound capable of modulating an effect of an element of the opioid system of the animal.

Treating, and compositions for treating, a condition and/or a symptom associated with an effect of at least one element of the opioid system in an animal by administering to the animal (i) a therapeutically effective amount of at least one microorganism and/or of a prebiotic thereof, where the microorganism is capable of modulating an effect of at least one element of the opioid system of the animal and (ii) a therapeutically effective amount of at least one compound capable of modulating an effect of an element of the opioid system of the animal.

The present invention discloses, in one embodiment, a method of using human induced pluripotent stem cells to generate three-dimensional human organ tissue for therapeutic drug toxicity and discovery⋅. In one embodiment, a high throughput microtiter plate is loaded with both wild type and Rett disease 3D spheroids and exposed to a drug library, and activity is measured and analyzed for disease rescue to wild type cell behavior.

The present invention discloses, in one embodiment, a method of using human induced pluripotent stem cells to generate three-dimensional human organ tissue for therapeutic drug toxicity and discovery⋅. In one embodiment, a high throughput microtiter plate is loaded with both wild type and Rett disease 3D spheroids and exposed to a drug library, and activity is measured and analyzed for disease rescue to wild type cell behavior.