We're developing new and existing drugs for inhalational therapy of mycobacterial disease. Our focus is on a novel approach to treat drug-resistant organisms, ensuring safety and efficacy using dry powders. The initial preclinical testing of dry powder inhaler products typically occurs in a murine model prior to movement to a larger animal model.
A significant limitation to this approach is the lack of suitable device technology for accurate and reproducible delivery of dry powders to small animals. The disposable dosators that we have developed are easy to manufacture, making them accessible and cost-effective for initial proof-of-concept studies in mice. The disposable nature allows their use in animal procedure rooms without concerns for cleaning, refilling, and weighing out materials for reusable devices.
Our future work will employ biotherapeutic moieties targeted to the pathogen that would avoid any effects on the host. This approach then can be tailored to the patient because it's pathogen specific. To prepare the disposable dosator and its filling components, take a 2.5 centimeter or 1 inch blunt stainless steel needle of 21 to 25 gauge.
Utilizing a precision sectioning saw or a belt sander, trim the plastic Luer part of the needle, leaving about 2 to 3 millimeters of the plastic Luer attached to the needle. Next, cut off approximately 1 to 1.5 centimeters from the tip of a 0.6 milliliter conical centrifuge tube. After that, fill this cut tip with 30 to 35 milligrams of the powder of interest.
For storing or transporting the powder, place the cutoff tube cap onto the cut tip containing the powder. Use paraffin film to wrap the cover, minimizing the powder's exposure to ambient moisture. To load the dosator, tamp the trimmed stainless steel needle into the powder bed in the cut tip as many times as required to achieve the desired dose.
Using a low-lint wiper, gently wipe the sides of the needle to remove any excess powder. Then take a 3.81 centimeter or 1.5 inch polypropylene needle of 16 to 20 gauge, and cautiously insert the loaded stainless steel needle into it, making sure not to dislodge any powder. Alternatively, use a 5.08 centimeter or 2 inch PTFE needle for the same.
To actuate the dosator, first draw back a disposable syringe to the desired volume based on the application. Then attach the syringe to the Luer lock on the polypropylene or PTFE needle before inserting the needle end of the dosator into the desired target. To analyze powder content and reproducibility, insert the dosator needle through a perforated rubber septum or paraffin film into a vial with a small quantity of liquid.
Forcefully depress the syringe plunger, expelling the powder from the device into the collection vial. Finally, analyze the powder solution in the vial using UV-visible spectrophotometry to monitor the dose of the powder released from the dosator. Four different spray dried powders, visualized using scanning electron microscopy, were considered for delivery using the demonstrated dosator.
The delivered dose, as a function of the number of Tamps in the powder bed, was obtained from UV-visible spectrophotometry of the powder solutions. Notably, all spray dried powders demonstrated a linear dose response from 1 to 4 Tamps. The first Tamp always incurred a larger dose of powder than subsequent Tamps.
When compared to the demonstrated 21-gauge stainless steel with a 16-gauge polypropylene dosator, a slight increase in achievable dose was observed using a 21-gauge stainless steel with a 20-gauge PTFE dosator for powder SD-1. As expected, the achievable dose of SD-1 decreased for a 22-gauge stainless steel, with an 18-gauge polypropylene dosator having a smaller inner needle diameter. A 25-gauge stainless steel with a 20-gauge polypropylene dosator further decreased the initial and subsequent Tamp doses.
This is a comparison of the four dosator systems that were evaluated, highlighting that the dosages can be customized to meet different dosage needs.
