System for delayed and pulsed release of biologically active substances
First Claim
1. A microencapsulated system for controlled release of entrapped biologically active substances prepared by the process comprising:
- entrapping a first substance within liposomes, wherein the liposomes have a predetermined rigidity, permeability, stability, and sensitivity to specific stimuli,encapsulating the liposomes within microcapsules permeable to solutions and the substance to be released but impermeable to scavenging components of the reticuloendothelial system, having a predetermined diameter, rigidity, stability, and being non toxic to the encapsulated liposomes and host if implanted, wherein the substance in the liposomes is released by exposure of the encapsulated liposomes to a specific stimulus selected from the group consisting of pH, sonication, temperature, high ionic strength solutions, bivalent metals, detergents, phospholipases, and light.
0 Assignments
0 Petitions
Accused Products
Abstract
A system for controlled release both in vivo and in vitro of entrapped substances, either at a constant rate over a period of time or in discrete pulses, is disclosed. Biologically active substances, such as drugs, hormones, enzymes, genetic material, antigens including viruses, vaccines, or inorganic material, such as dyes and nutrients, are entrapped in liposomes which are protected from the biological environment by encapsulation within semi-permeable microcapsules. Release of the entrapped substance into the surrounding environment is governed by the permeability of both the liposome and microcapsule walls to the substance. Permeability of the liposome is engineered by modifying the composition and method for making the liposomes, thereby producing liposomes which are sensitive to a specific stimuli such as temperature, pH, or light; or by including a phospholipase within some or all of the liposomes or the microcapsule; or by destabilizing the liposomes to break down over a period of time; or by any combination of these features.
127 Citations
24 Claims
-
1. A microencapsulated system for controlled release of entrapped biologically active substances prepared by the process comprising:
-
entrapping a first substance within liposomes, wherein the liposomes have a predetermined rigidity, permeability, stability, and sensitivity to specific stimuli, encapsulating the liposomes within microcapsules permeable to solutions and the substance to be released but impermeable to scavenging components of the reticuloendothelial system, having a predetermined diameter, rigidity, stability, and being non toxic to the encapsulated liposomes and host if implanted, wherein the substance in the liposomes is released by exposure of the encapsulated liposomes to a specific stimulus selected from the group consisting of pH, sonication, temperature, high ionic strength solutions, bivalent metals, detergents, phospholipases, and light. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
-
-
10. A method for making a microencapsulated system for controlled release of entrapped biologically active substances comprising:
-
providing a first biologically active substance, entrapping the first substance within liposomes, wherein the liposomes have a predetermined rigidity, permeability, stability, and sensitivity to stimuli selected from the group consisting of pH, sonication, temperature, high ionic strength solutions, bivalent metals, detergents, phospholipases, and light, such that exposure to a stimulus effects release of the entrapped substance from the liposomes, and, encapsulating the substance-containing liposomes within microcapsules, wherein the microcapsules are permeable to solutions and the substance to be released but impermeable to scavenging components of the reticuloendothelial system, have a predeterined diameter, rigidity, stability, and are non-toxic to the encapsulated liposomes and host if implanted. - View Dependent Claims (11, 12, 13, 14)
-
-
15. A method for controlled release of an entrapped biologically active substance comprising:
releasing by exposure to a specific stimuli a first biologically active substance entrapped within encapsulated liposomes having a predetermined rigidity, permeability, stability, and sensitivity to specific stimuli selected from the group consisting of pH, sonication, temperature, high ionic strength solutions, bivalent metals, detergents, phospholipases, and light, such that exposure to a stimulus effects release of the entrapped substance from the liposomes, wherein the permeability of the liposomes has been disrupted after encapsulation within microcapsules that are permeable to solutions and the substance to be released but impermeable to scavenging components of the reticuloendothelial system, having a predetermined diameter, rigidity, stability, and non-toxicity to the encapsulated liposomes and host if implanted. - View Dependent Claims (16, 17, 18, 19, 20, 21, 22, 23, 24)
Specification