Matrices for drug delivery and methods for making and using the same

Abstract

In one aspect, biocompatible matrices such as sol-gels encapsulating a reaction center may be administered to a subject for conversion of prodrugs into biologically active agents. In certain embodiments, the biocompatible matrices of the present invention are sol-gels. In one embodiment, the enzyme L-amino acid decarboxylase is encapsulated and implanted in the brain to convert L-dopa to dopamine for treatment of Parkinson's disease.

Description

1. RELATED APPLICATION INFORMATION[0001] This Application claims the benefit of priority under 35 U.S.C. section 119(e) to Provisional Application No, 60 / 119,828, filed Feb. 12, 1999.2. INTRODUCTION[0002] Many clinical conditions, deficiencies, and disease states may be remedied or alleviated by providing to a patient beneficial biologically active agents or removing from the patient deleterious biologically active agents. In many cases, provision of beneficial agents or removal of deleterious ones may restore or compensate for the impairment or loss of function or homeostasis. An example of a disease or deficiency state whose etiology includes loss of such an agent include Parkinson's disease, in which dopamine production is diminished. The impairment or loss of such agents may result in the loss of additional metabolic functions.[0003] Parkinson's disease, one of many motor system disorders, results in symptoms such as tremor, bradykinesia, and impaired balance. Keller in Handbook...

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Problems solved by technology

The impairment or loss of such agents may result in the loss of additional metabolic functions.

Parkinson's disease, one of many motor system disorders, results in symptoms such as tremor, bradykinesia, and impaired balance.

Second, monoamine oxidase inhibitors (MAO) reduce the rate of doparnine breakdown catalyzed by monoamine oxidase enzymes and thereby increase the dopamine levels in the brain.

With respect to chemical methods, delivery to the striatal region of any biologically active agent, such as dopamine, MAO inhibitors, or anticholinergics, is complicated, in part, because of the presence of the blood-brain barrier, which may result in low bioavailability of any such agents.

As an alternative, direct administration of dopamine into the central nervous system may require the frequent and repeated use of invasive procedures which compromise the integrity of the blood-brain barrier.

Even with the careful use of sterile procedures, there is risk of infection.

It has been reported that even in intensive care units, intracerebroventricular catheters used to monitor intracranial pressure become infected with bacteria after about three days.

In addition to the risk of infection, there seems to be some risk associated with the infusion procedure.

Surgical tissue transplantation suffers from a number of factors such as immunogenic complications, delayed improvement results, and low tissue survival rates of around 10%.

The use of fetal tissue has formidable hurdles, including the failure to reestablish the normal neural circuitry, high mortality and morbidity associated with the transplant procedure, and the ethical issue of human fetal tissue research.

Adrenal cells are generally only implanted in patients less than 60 years of age, as the adrenal gland of older patients may not contain sufficient dopamine-secreting cells, which limits the usefulness of the procedure as a treatment method because the disease most often affects the elderly.

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