Polymeric Depots Research Articles

Defining the Role of Ultrasound in Drug Delivery

Ultrasound is a very effective modality for drug delivery because energy that is noninvasively transmitted through the skin can be focused on a specific location and employed to release drug at that site. Most of the drug delivery techniques employ one or both of the results of ultrasonic insonation — the generation of thermal energy, called hyperthermia, or the oscillation of gas bubbles, called acoustic cavitation. Cavitation perturbs cell membrane structures via several modes and increases the permeability to drugs or other solutes. Micro-convection, caused by stable cavitation, shears cell membranes. The shock waves and fluid jets of inertial cavitation disrupt and pierce cell membranes. While intense cavitation can lyse cells, moderate cavitation can transiently increase membrane permeability without lysis or permanent damage.Cavitation events can increase the permeability of larger tissue systems, such as skin or capillary walls. In skin, cavitation appears to transiently disrupt the lipid organization of the stratum corneum, as well as to form pores. In bacteria, cavitation is implicated in increasing the cell wall permeability towards antibacterials. Cavitation events also increase the rate of drug transport in general by superseding the slow diffusion process with convective transport processes. Ultrasound increases the transport of proteins into blood clots, of antibacterials through alginate, and of drugs from polymeric depots. Drugs can also be released ultrasonically from liposomes and micelles that circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Gas filled microbubbles in the circulatory system cavitate upon insonation and disrupt surrounding cells and membranes, thus allowing the passage of drugs into the targeted tissue.The unique advantages of ultrasonic drug delivery have been employed in several tissue systems, including dermal and transdermal delivery, localized delivery to tumors, and delivery to selected organs, such as the heart, eyes, and lungs.The scope of this review article covers the use of ultrasound in delivering drugs to targeted tissues, with emphasis on drug release from liposomes, micelles and polymeric depots.