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 III 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

[0006]In another aspect, the present disclosure provides a method of delivering two or more agents to a solid tissue of a subject, comprising: (a) administering at least one of said two or more agents to said subject systemically; and (b) delivering at least one of said two or more agents to said solid tissue with at least one microdialysis probe or at least one needle, wherein said agent(s) administered in (a) is different from said agent(s) delivered in (b). In some case, step (a) is performed prior to step (b). In some other cases, step (a) is performed after step (b). The method may further comprise evaluating at least one effect of the agents on the solid tissue.

[0007]In some embodiments, the agent(s) delivered in (a) or (b) is selected from the group consisting of an anti-angiogenic agent, a kinase inhibitor, an inhibitor of metabolic pathway targets that are preferentially expressed in cancer cells, or an epigenetic modifier. In some other embodiments, the agent(s) delivered in (a) or (b) comprises a small molecule anti-cancer agent. In some embodiments, the agent(s) delivered in (a) comprises an antibody or antibody drug conjugate. In some embodiments, the agent(s) delivered in (b) comprises a small interfering RNA, an antisense RNA or a small molecule anti-cancer agent. At least one of the agents delivered in step (b) may be delivered at different concentrations to different regions of the solid tissue. Alternatively, at least one of the agents delivered in step (b) may be delivered in multiple doses to a same region of the solid tissue. The agent(s) administered in step (a) and the agent(s) delivered in step (b) may have a synergistic effect on the solid tissue. The agent(s) may be present at a concentration below the therapeutic effective concentration.

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 III 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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