Design of Microbubbles for Gene/Drug Delivery

Abstract

The role of ultrasound contrast agents (UCA) initially designed for diagnosis has evolved towards a therapeutic use. Ultrasound (US) for triggered drug delivery has many advantages. In particular, it enables a high spatial control of drug release, thus potentially allowing activation of drug delivery only in the targeted region, and not in surrounding healthy tissue. Moreover, UCA imaging can also be used firstly to precisely locate the target region to, and then used to monitor the drug delivery process by tracking the location of release occurrence. All these features make UCA and ultrasound attractive means to mediate drug delivery. The three main potential clinical indications for drug/gene US delivery are (i) the cardiovascular system, (ii) the central nervous system for small molecule delivery, and (iii) tumor therapy using cytotoxic drugs. Although promising results have been achieved in preclinical studies in various animal models, still very few examples of clinical use have been reported. In this chapter will be addressed the aspects pertaining to UCA formulation (chemical composition, mode of preparation, analytical methods…) and the requirement for a potential translation into the clinic following approval by regulatory authorities.

Ultrasound‐microbubble cavitation facilitates adeno‐associated virus mediated cochlear gene transfection across the round‐window membrane

“…US has long been recognized as a useful tool for targeting material delivery for therapeutic applications, including gene transfection (see reviews 26,31,32,[39][40][41] ). MBs have been used as imaging enhancers since the 1990s.…”

“…In addition to medication delivery, 26,31 the use of USMB cavitation for gene transfection via plasmid DNA, siRNA, and miRNA has been investigated. 27,28,32 USMB-mediated AAV gene transfection in the rat retina has also been reported. 33 In that application, however, AAV was injected into the subretinal space before USMB was applied.…”

Ultrasound and Microbubbles for Targeted Drug Delivery to the Lung Endothelium in ARDS: Cellular Mechanisms and Therapeutic Opportunities

“…Several attempts have been made to bind cargo (i.e., drugs or plasmids) to the microbubble shell using electrostatic or covalent interactions [128]. Due to the proximity of the cargo to the microbubble shell, it is speculated that this approach leads to enhanced delivery efficacy due to cavitation effects [129]. In addition, the release of cargo could be limited to the area of insonation, thus reducing any adverse side-effects related to free circulating drug [129].…”

“…Due to the proximity of the cargo to the microbubble shell, it is speculated that this approach leads to enhanced delivery efficacy due to cavitation effects [129]. In addition, the release of cargo could be limited to the area of insonation, thus reducing any adverse side-effects related to free circulating drug [129]. Plasmids, which have an inherent negative charge, can be bound onto the shells of cationic lipid microbubbles using electrostatic interactions.…”

“…Similar to electrostatic or covalent binding, embedding the cargo inside the microbubble shell could have a protective effect on the cargo, preventing its early degradation and prolonging its half-life inside the body [129]. Different types of cargo have been embedded inside the microbubble shell.…”