Sensitizing Conventional Drug Vehicles to Ultrasound for Improved Delivery

A successful drug delivery system can be defined as a platform that enables the introduction of the optimal drug dose to a specific tissue for an intended duration. As the definition suggests, rigorous control over drug deposition is a necessity. Drug-based therapy historically included the introduction of a drug to the bloodstream, mainly using the digestion route or injection. This traditional delivery method has no specificity or control over delivery to the diseased tissue. Furthermore, administration of the free drug in the bloodstream results in a narrow therapeutic window where only small doses of drugs are used to prevent detrimental drug bioeffects. One of the significant accomplishments in pharmaceutics was designing drug carriers that can encapsulate high payloads of medicines and reduce drug toxicities in the bloodstream. This accomplishment was mainly a fruit of cancer research where encapsulation of highly toxic chemotherapeutics is critical. In the 1990s and 2000s, drug release from carriers and successful drug targeting were major research areas. One of the promising drug delivery platforms introduced in that era was image- guided drug delivery (IGDD). IGDD is a platform that uses a type of external energy source to activate and control drug release from stimuli-sensitive drug carriers. One of the critical choices in IGDD platforms is selecting a suitable external energy source. Ultrasound (US) has been one of the primary modalities for IGDD since it is spatiotemporally precise and cost-effective. Despite successful preclinical and clinical data in the ultrasound-mediated drug delivery field, there is still no clinically approved ultrasound-sensitive drug carrier. In this thesis, we report novel methods to make conventional drug delivery vehicles sensitive to ultrasound for producing safe and efficient ultrasound-responsive drug vehicles. We chose clinically successful drug vehicles for this purpose and delved deeper into their material chemistry to manipulate and sensitize them to ultrasound energy. We hypothesized that by introducing ultrasound-sensitive agents to traditional drug vehicles, we could build ultrasound-sensitive drug carriers suitable for drug delivery and imaging. The designed drug carriers have the potential to be used in image-guided drug delivery platforms. Our results suggest that we can create ultrasound-sensitive particles and agents suitable for theranostic/dual imaging applications by incorporating ultrasound cavitation nuclei in a drug delivery system.