Methods for drug delivery

Abstract

Methods and devices for delivering an agent to a solid tissue in vivo for assessment of efficacy are described. One method involves withdrawing of a needle from and injecting of the agent into the solid tissue; another method involves delivering the agent using a plurality of microdialysis probes to a solid tissue.

Description

CROSS-REFERENCE[0001]This application claims the benefit of priority under 35 U.S.C. section 119(e) to U.S. Provisional Application 61 / 553,003, filed Oct. 28, 2011; and U.S. Provisional Application 61 / 680,847, filed Aug. 8, 2012; the contents of which are incorporated by reference in their entirety.BACKGROUND OF THE INVENTION[0002]Numerous cancer-related therapeutics are under preclinical, phase I or phase II clinical trial and evaluations at any particular time; however, most of them will fail to advance. In fact, numerous drug candidates fail in the preclinical test, and it is estimated that more than 90% of cancer-related therapeutics will fail phase I or II clinical trial evaluation. The failure rate in phase III trials is almost 50%, and the cost of new drug development from discovery through phase Ill trials is between $0.8 billion and $1.7 billion and can take between eight and ten years.[0003]In addition, many subjects fail to respond even to standard drugs that have been sh...

AI Technical Summary

Benefits of technology

The use of microdialysis probes as a delivery tool has advantages such as being an enclosed system, not dependent upon delivery of a liquid volume, allowing for easy and controlled delivery of agents. The semi-permeable membrane surrounding the probe allows liquid to be filled and distributed evenly along the probe membrane when injecting into a solid tissue. Multiple or timed dosing over an extended periods of time can be achieved by leaving the probes in the solid tissue. The amount of agents delivered can be accurately determined by analyzing the amount of agent in the perfusate and dialysate. The length of the probe / semi-permeable membrane can be customized to target various size tumors or length of targeting zone within a tumor. An array of linear microdialysis probes can be designed to target the proliferating zone in solid tumor xenografts, as well as avoiding the central regions necrosis. The use of microdialysis probes can help better sampling of multiple zones, including the entire dimension of a solid tumor, and can help coax contact-inhibited cells into cycling in order to kill them using checkpoint inhibition / DNA damage, or activate cell signal pathways that have been shut down in non-proliferative zones.

Problems solved by technology

Numerous cancer-related therapeutics are under preclinical, phase I or phase II clinical trial and evaluations at any particular time; however, most of them will fail to advance.

In fact, numerous drug candidates fail in the preclinical test, and it is estimated that more than 90% of cancer-related therapeutics will fail phase I or II clinical trial evaluation.

The failure rate in phase III trials is almost 50%, and the cost of new drug development from discovery through phase Ill trials is between $0.8 billion and $1.7 billion and can take between eight and ten years.

In addition, many subjects fail to respond even to standard drugs that have been shown to be efficacious.

For reasons that are not currently well understood or easily evaluated, individual subjects may not respond to standard drug therapy.

One significant challenge in the field of oncology is to exclude treatment selection for individual subjects having cell autonomous resistance to a candidate drug to reduce the risk of unnecessary side effects.

A related problem is that excessive systemic concentrations are required for many oncology drug candidates in efforts to achieve a desired concentration at a tumor site, an issue compounded by poor drug penetration in many under-vascularized tumors (Tunggal et al., 1999 Clin. Canc. Res. 5:1583).

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