Controlled local delivery of chemotherapeutic agents for treating solid tumors
First Claim
1. A chemotherapeutic composition comprisinga biocompatible polymeric matrix and a water insoluble, lipid insoluble chemotherapeutic agent, which does not cross the blood-brain barrier,wherein the agent is incorporated into and released from the polymeric matrix by degradation of the matrix or diffusion of the agent out of the matrix over a period of time of at least eight hours in an amount effective to inhibit growth of a solid tumor when administered to the tumor.
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Abstract
A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended time period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed. The examples demonstrate the efficacy of paclitaxel and camptothecin delivered in polymeric implants prepared by compression molding of biodegradable and non-biodegradable polymers, respectively. The results are highly statistically significant.
499 Citations
18 Claims
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1. A chemotherapeutic composition comprising
a biocompatible polymeric matrix and a water insoluble, lipid insoluble chemotherapeutic agent, which does not cross the blood-brain barrier, wherein the agent is incorporated into and released from the polymeric matrix by degradation of the matrix or diffusion of the agent out of the matrix over a period of time of at least eight hours in an amount effective to inhibit growth of a solid tumor when administered to the tumor.
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8. A method of administering to a patient in need of treatment a water insoluble, lipid insoluble chemotherapeutic agent comprising
administering the chemotherapeutic agent locally adjacent or in a solid tumor, wherein the agent is incorporated into and released from a polymeric matrix by degradation of the polymer matrix or diffusion of the agent out of the matrix over a period of time of at least eight hours, wherein in an amount effective to inhibit growth of the solid tumor.
Specification