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.

What is claimed is: 
     
         1 . (canceled) 
     
     
         2 . A method of delivering one or more agents to a solid tissue of a subject, comprising:
 (a) inserting one or more needles to said solid tissue; and   (b) delivering said one or more agents to said solid tissue by withdrawing said one or more needles from said solid tissue and injecting said one or more agents into said solid tissue.   
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 2 , further comprising evaluating an effect of at least one of said one or more agents on said solid tissue. 
     
     
         5 .- 16 . (canceled) 
     
     
         17 . The method of  claim 2 , wherein at least one of said one or more agents is delivered to a same region of said solid tissue in multiple doses. 
     
     
         18 . The method of  claim 17 , wherein any two of said multiple doses are separated by a selected period of time. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 2 , wherein said one or more agents comprises a chemotherapeutic agent. 
     
     
         22 .- 25 . (canceled) 
     
     
         26 . The method of  claim 2 , wherein said one or more agents comprises an agent selected from the group consisting of a protein, a peptide, a peptidomimetic, an antibody, a small molecule, a small interfering RNA-encoding polynucleotide, an antisense RNA-encoding polynucleotide, or a ribozyme-encoding polynucleotide. 
     
     
         27 . The method of  claim 2 , wherein said one or more agents comprises a fluorescent dye. 
     
     
         28 . The method of  claim 2 , wherein two or more agents are delivered simultaneously to a same region within said solid tissue. 
     
     
         29 . The method of  claim 2 , wherein two or more agents are delivered sequentially to a same region within said solid tissue. 
     
     
         30 . The method of  claim 2 , wherein two or more agents are delivered to different regions within said solid tissue. 
     
     
         31 . The method of  claim 2 , wherein at least one agent is delivered to different regions within said solid tissue at different concentrations. 
     
     
         32 . The method of  claim 2 , wherein said solid tissue comprises a tumor. 
     
     
         33 . (canceled) 
     
     
         34 . The method of  claim 32 , wherein said tumor is selected from the group consisting of a primary tumor, an invasive tumor and a metastatic tumor. 
     
     
         35 .- 37 . (canceled) 
     
     
         38 . The method of  claim 4 , wherein said evaluating is performed in vitro. 
     
     
         39 . The method of  claim 4 , wherein said evaluating is performed in vivo. 
     
     
         40 . (canceled) 
     
     
         41 . The method of  claim 4 , wherein said evaluating comprises detecting activity or toxicity or lack thereof of at least one of said one or more agents, in separate regions of said solid tissue. 
     
     
         42 . The method of  claim 4 , wherein said evaluating comprises detecting the activity or toxicity of at least two of said agents, in a same region of said solid tissue. 
     
     
         43 . The method of  claim 42 , wherein said activity or toxicity is synergistic. 
     
     
         44 . The method of  claim 42 , wherein said activity or toxicity is additive. 
     
     
         45 . The method of  claim 4 , wherein said evaluating comprises imaging said solid tissue. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 45 , wherein said imaging occurs during, or after introduction of said agents. 
     
     
         48 . The method of  claim 4 , wherein said evaluating comprises analyzing at least one analyte selected from the group consisting of: a biomarker for tumor cell death, a biomarker for cell signal changes, a biomarker for proliferative or miotic changes, the one or more agents delivered to the solid tissue and metabolite(s) of the one or more agents delivered to the solid tissue, or any combination thereof. 
     
     
         49 .- 50 . (canceled) 
     
     
         51 . The method of  claim 2 , further comprising marking sites of insertions. 
     
     
         52 . The method of  claim 51 , wherein said sites of insertions are marked by at least one position marker. 
     
     
         53 . The method of  claim 52 , wherein said at least one position marker comprises a dye. 
     
     
         54 . The method of  claim 53 , wherein said dye and at least one additional agent is delivered to a same region within said solid tissue. 
     
     
         55 . (canceled) 
     
     
         56 . The method of  claim 2 , wherein said inserting is carried out with a needle array device. 
     
     
         57 .- 62 . (canceled) 
     
     
         63 . The method of  claim 2 , wherein each of said one or more needles comprises a different agent. 
     
     
         64 . The method of  claim 2 , wherein at least two of said needles each comprises a same agent at different concentrations. 
     
     
         65 .- 66 . (canceled) 
     
     
         67 . The method of  claim 2 , wherein at least one of said one or more agents is a cancer therapeutic agent. 
     
     
         68 . The method of  claim 4 , wherein said evaluating comprises detecting cell apoptosis after delivering a cancer therapeutic agent. 
     
     
         69 .- 73 . (canceled) 
     
     
         74 . The method of  claim 2 , wherein said withdrawing one or more needles and injecting one or more agents are carried out simultaneously. 
     
     
         75 . (canceled) 
     
     
         76 . The method of  claim 2 , wherein the rate of injecting one or more agents is between about 0.1 μl/min and about 10 μl/min. 
     
     
         77 .- 79 . (canceled) 
     
     
         80 . The method of  claim 2 , wherein the rate of withdrawing one or more needles is between about 0.1 mm/min and about 5 mm/min. 
     
     
         81 .- 82 . (canceled) 
     
     
         83 . The method of  claim 2 , wherein said one or more needles comprise at least five needles. 
     
     
         84 .- 88 . (canceled) 
     
     
         89 . The method of  claim 2 , wherein outside said solid tissue said one or more agents is undetectable, outside said solid tissue. 
     
     
         90 . The method of  claim 2 , wherein said one or more agents is introduced in an amount that is less than a minimal dose required to produce a detectable effect in said solid tissue. 
     
     
         91 . The method of  claim 2 , wherein said one or more agents is present in said solid tissue at a therapeutically effective concentration. 
     
     
         92 .- 97 . (canceled) 
     
     
         98 . The method of  claim 2 , wherein the subject is an animal. 
     
     
         99 . The method of  claim 2 , wherein the subject is a human. 
     
     
         100 . The method of  claim 4 , wherein said evaluating comprises an evaluation method selected from the group consisting of: selecting at least one of said one or more based on said evaluating, deselecting at least one of said one or more agents based on said evaluating, and prioritizing at least two of said agents based on said evaluating. 
     
     
         101 . The method of  claim 4 , wherein said subject is one of a plurality of subjects. 
     
     
         102 .- 135 . (canceled) 
     
     
         136 . The method of  claim 2 , wherein outside said solid tissue said one or more agents is present at less than a minimal effective dose.