Toward a closed-loop subcutaneous delivery of L-DOPA

TL;DR

This paper proposes a novel closed-loop subcutaneous delivery system for L-DOPA to improve Parkinson's disease treatment by bypassing gastrointestinal issues and controlling blood-brain barrier competition.

Contribution

It introduces a new closed-loop controlled pump for continuous subcutaneous L-DOPA delivery, addressing absorption and blood barrier challenges.

Findings

Model-based evaluation shows potential for improved drug delivery.

Closed-loop control can maintain optimal L-DOPA levels.

Bypasses gastrointestinal absorption issues.

Abstract

L-DOPA has been the gold standard treatment for Parkinson's disease since 50 years. Being the direct biochemical precursor of dopamine, L-DOPA is effectively converted in the brain, but two major phenomena reduce its therapeutic action: i) competition with amino acids in the gut wall and in the blood brain barrier and ii) its fast kinetics (absorption, distribution, metabolism, and elimination). Continuous administration of L-DOPA, such as jejunal pumps, have addressed the issue of fast absorption. Considering a subcutaneous delivery of L-DOPA allows to bypass the gastrointestinal tract and avoid competition with dietary amino acids. Remains the competition at the blood barrier between amino acids and L-DOPA, which we address by proposing a closed-loop controlled, continuous subcutaneous delivery pump. In the proof-of-concept format, the delivery strategy evaluated on comprehensive model of L-DOPA kinetics, holds the promise of improving the treatment of late-stage Parkinson's disease patients.