https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2884%2980836-4

The organ uptake of intravenously administered colloidal particles can be altered using a non-ionic surfactant (Poloxamer 338).

Drug delivery compositions yeild new and unexpected degrees of stabilization, solubilization and delivery of incorporated medicaments, drugs, or other physiologically-active compounds. The compositions enable administration of drugs and other medically useful compounds via a variety of routes. More particularly, a drug delivery system or composition including one or more monomeric or polymerized surface active agents allows for rapid dissolution and smooth liberation of any desired incorporated drug or combinations, and the method of preparing the drug composition. In one embodiment, the physiologically-active compound is encapsulated by a coacervate-derived film, and the finished product is suitable for transmucosal administration. Other formulations of this invention may be administered via inhalation, oral, parenteral and by transdermal and transmucosal routes.

Drug delivery compositions and methods

In accordance with the present invention, there are provided compositions and methods useful for the in vivo delivery of substantially water insoluble pharmacologically active agents (such as the anticancer drug paclitaxel) in which the pharmacologically active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacologically active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diameter of less than about 1 micron. The use of specific composition and preparation conditions (e.g., addition of a polar solvent to the organic phase), and careful selection of the proper organic phase and phase fraction, enables the reproducible production of unusually small nanoparticles of less than 200 nm diameter, which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insoluble drug coated with a protein, and free protein to which molecules of the pharmacological agent are bound. This results in a unique delivery system, in which part of the pharmacologically active agent is readily bioavailable (in the form of molecules bound to the protein), and part of the agent is present within particles without any polymeric matrix therein.

Formulations of pharmacological agents, methods for the preparation thereof and methods for the use thereof

A brominated perfluorocarbon emulsion non-toxic for internal and intravenous use in animals including humans for use as an oxygen transport medium and as a tumor and other element contrast enhancement medium is stable with very small size characteristics for extended periods in excess of eighteen months and after sterilization, with a stabilizing component selected from the class comprising steroid hormones, tocopherols, cholesterols and their combinations. An anti-oxidizing component enhances delivery in oxygen transport.

Brominated perfluorocarbon emulsions for internal animal use for contrast enhancement and oxygen transport

Stable emulsions of highly fluorinated organic compounds for use as oxygen transport agents, "artificial bloods" or red blood cell substitutes and as contrast agents for biological imaging. The emulsions comprise a highly fluorinated organic compound, an oil that is not substantially surface active and not significantly soluble in water, a surfactant and water.

Stable emulsions of highly fluorinated organic compounds

Synthetic whole blood useful as a substitute for whole natural mammalian blood and method of making the same. The method of manufacture yields a composition of matter comprised of a two phase coacervate system. The claimed system successfully substantially duplicates the two phase heterogeneous physico-chemical system of naturally occurring whole mammalian blood. Also disclosed is a phase of the claimed method of manufacture which produces a composition of matter, useful as a substitute for naturally occurring hematocrit.

Synthetic whole blood and a method of making the same

The method of this invention yields a two phase liquid aqueous system which replicates the two phase heterogeneous physico-chemical system of naturally securing whole human blood. The method produces: (1) a composition of matter which comprises an oxygen transport solution; (2) when pyridoxalated-polymerized hemoglobin and other specific additives are incorporated, said composition comprises a synthetic blood useful as a physiological substitute for human blood; and (3) when said blood substitute is processed further, yields a microencapsulated composition with time released characteristics that can transport oxygen. The invention overcomes the obstacles that have prevented the use of pyridoxalated-polymerized hemoglobin and other forms of modified hemoglobin in the preparation of oxygen transport solutions.

Substitute for human blood and a method of making the same

A composition and a method of making a whole blood substitute are disclosed. The claimed invention duplicates the two phase heterogeneous physico-chemical system of natural whole blood and accordingly, is capable of carrying out virtually all of the physiological functions of whole blood. Albumin dispersed in a solution composed of distilled water, sodium chloride and urea, and to which a surface active agent such as lecithin is subsequently added, constitutes the preferred method of preparing the two phase aqueous liquid system on which this invention is based. Other ingredients necessary to the manufacture of the claimed composition of matter include stroma free hemoglobin, an appropriate sterol, electrolytes and proteins. Emulsification of the two phase aqueous liquid system and the additives given immediately above completes the preparation of the claimed synthetic whole blood. The method of manufacture described in this disclosure also provides for the separation of the phases of the two phase aqueous liquid system. Separation of the coacervate phase from the external equilibrium phase may be carried out prior to the introduction of the additives referred to above. In the preferred procedure, separation takes place after emulsification has been completed. Introduction of the claimed synthetic whole blood into the circulation is accomplished through intravenous transfusion. When introduced into the circulation, the coacervate phase of this invention will serve the functions of normally occuring hematocrit.

Bernard Ecanow

Papers

Synthetic whole blood and a method of making the same

Substitute for human blood and a method of making the same

Synthetic whole blood

Powdered Particle Interactions: Suspension Flocculation and Caking I

Ferguson Principle and the Critical Micelle Concentration