The invention relates to a new and improved pharmaceutical composition and method for delivery of therapeutic agents. The methods and composition of the invention can be used with several therapeutic agents and can achieve site specific delivery of a therapeutic substance. This can allow for lower doses and for improved efficacy with drugs which traditionally reach targeted sites and can result in utility for agents such as oligonucleotides which are plagued with problems in reaching targeted sites in necessary therapeutic levels. The delivery system includes gas-filled microbubbles formed in a nitrogen-free environment. Microbubbles formed through sonication in a nitrogen-free environment are smaller and more stable than microbubbles sonicated in the presence of room air.