Which of the following techniques is most likely to increase the diffusion of a hydrophilic peptide drug across the skin?

To increase the diffusion of a hydrophilic peptide drug across the skin, several techniques can be employed. Here are some common methods:

1. Microneedle Technology: This involves the use of tiny needles that penetrate the outer layer of the skin, allowing the peptide drug to bypass the stratum corneum, which is usually a barrier to large and hydrophilic molecules.

2. Chemical Permeation Enhancers: Certain chemical agents can disrupt the lipid structure of the stratum corneum, enhancing the permeability of the skin for hydrophilic compounds. Examples include surfactants and solvents like ethanol.

3. Iontophoresis: This technique uses electrical currents to drive charged molecules (like many peptides) across the skin, significantly increasing their rate of diffusion.

4. Ultrasound (Sonophoresis): The application of ultrasonic waves can create cavitation and microstreaming effects, temporarily disrupting the skin barrier and facilitating the absorption of hydrophilic drugs.

Among these techniques, microneedle technology is often considered the most effective for enhancing the diffusion of hydrophilic peptide drugs as it provides a direct pathway through the skin barrier while minimizing pain and discomfort.