Methods for lymphatic delivery of active agents

A method of treating a subject with a disease comprising one or more sites of lymphadenitis by administering one or more bioactive agents to the one or more sites of lymphadenitis comprising:

• (a) applying one or more delivery devices having between 2 and 50,000 delivery structures to one or more sites of a skin of a subject having lymphatic vasculature, wherein the delivery device contacts one or more layers of epidermis with one or more reversible permeability enhancers comprising a chemical, physical or electrical permeability enhancer that induces reversible increase in the permeability of one or more barrier cells of the epidermis to at least one or more bioactive agents;
• (b) administering a total liquid dosage in between 2 and 50,000 sub-doses of the one or more bioactive agents at a controlled administration flow rate of from about 0.01 μl/hr to about 100 μl/hr per each of the delivery structures at a total combined controlled administration flow rate of about 0.02 μl/hr/cm2 to about 50,000 μl/hr/cm2 based on a total surface area of the one or more delivery devices that is in contact with the skin of the subject;
• wherein each sub-dose of the one or more bioactive agents is independently administered, in an administering step, to a plurality of independent depths ranging from about 1 μm to about 500 μm beyond a most superficial surface layer of the epidermis of the subject prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis;
• wherein following the administering step. the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature compared to intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents;
• and
• wherein after administration and uptake, the one or more bioactive agents circulates through the lymphatic vasculature to one or more secondary lymphatic tissues comprising one or more lymph nodes, thereby administering the one or more bioactive agents to the one or more sites of lymphadenitis.

A method of treating a subject with a disease comprising one or more sites of lymphadenitis by administering one or more bioactive agents to the one or more sites of lymphadenitis comprising:

• (a) applying one or more delivery devices having between 2 and 50,000 delivery structures to one or more sites of a skin of a subject having lymphatic vasculature, wherein the delivery device contacts one or more layers of epidermis with one or more reversible permeability enhancers comprising a chemical, physical or electrical permeability enhancer that induces reversible increase in the permeability of one or more barrier cells of the epidermis to at least one or more bioactive agents:
• (b) administering a total liquid dosage in between 2 and 50,000 sub-doses of the one or more bioactive agents at a controlled administration flow rate through the delivery device;
• wherein each sub-dose of the one or more bioactive agents is independently administered, in an administering step, to a plurality of independent depths ranging from about 1 μm to about 500 μm beyond a most superficial surface layer of the epidermis of the subject prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis;
• wherein following the administering step, the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature compared to intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents;
• and
• wherein after administration and uptake, the one or more bioactive agents circulates through the lymphatic vasculature to one or more secondary lymphatic tissues comprising one or more lymph nodes, thereby administering the one or more bioactive agents to the one or more sites of lymphadenitis.