MICROFABRICATED PARTICLES AND METHOD FOR TREATING SOLID TUMORS
First Claim
1. Asymmetric microparticles for intravenous administration in treating tumors, having:
- (i.) uniform sizes, e.g., in the range 0.5 to 10 μ
m, (ii.) at least one internal reservoir which communicates through at least one pore with the front face of said particle, (iii.) each reservoir containing a releasable cytotoxic agent, (iv.) said pore and/or reservoir filled or covered with release-delaying material, and (v.) a layer of ligand molecules chemically grafted to the same face of the particle as the pore openings.
4 Assignments
0 Petitions
Accused Products
Abstract
Microfabricated, asymmetrical, reservoir-containing particles for use in the intravenous delivery of cytotoxic agents such as melittin to tumors is disclosed. The particles have a selected shape and uniform dimensions preferably in the 1 μm to 10 μm range. The reservoirs open to the face of the particle and are filled with a solution or suspension of the therapeutic agent and selected excipients. The drug/excipient solution may be dried by standard techniques. The excipients are selected to delay the dissolution/release of the agent from the particle reservoirs for 1-48 hours after the particle suspension is rehydrated and injected. Alternatively, the pore is plugged with an erodable material or covered with a semipermeable membrane. The face of the particle is grafted with a layer of specific ligands designed to quickly bind the particle to the surface of either tumor cells or the vascular endothelial cells, which form tumor capillaries. The cytolytic agent, which is released from the reservoirs after binding, is presented directly to the surface membranes of target cells. The locally high concentration of cytolytic agent achieved in the circumscribed volume between the face of the particle and the juxtaposed cell provides for efficient entry of the cytolytic agent directly into the surface membrane of the target cell leading to cell lysis ans death. Also disclosed are microfabrication methods for making such particles and a method of treating cancer patients with such particles.
45 Citations
44 Claims
-
1. Asymmetric microparticles for intravenous administration in treating tumors, having:
-
(i.) uniform sizes, e.g., in the range 0.5 to 10 μ
m,(ii.) at least one internal reservoir which communicates through at least one pore with the front face of said particle, (iii.) each reservoir containing a releasable cytotoxic agent, (iv.) said pore and/or reservoir filled or covered with release-delaying material, and (v.) a layer of ligand molecules chemically grafted to the same face of the particle as the pore openings. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27)
-
-
28. A method for treating patients with solid tumors, wherein asymmetric microparticles, having:
-
(vi.) uniform sizes, e.g., in the range 0.5 to 10 μ
m,(vii.) at least one internal reservoir which communicates through at least one pore with the front face of said particle, (viii.) said internal reservoir containing a releasable cytotoxic agent, (ix.) said pore and/or reservoir filled or covered with release-delaying material, and (x.) a layer of ligand molecules chemically grafted to the same face of the particle as the pore openings are injected intravenously into the patient. - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44)
-
Specification