Increasing the clinical efficacy of toxic chemotherapy drugs such as cisplatin (CDDP), via targeted drug delivery, is a key area of research in cancer treatment. In this study, CDDP-loaded poly(lactic-co-glycolic acid) (PLGA) polymeric nanoparticles (NPs) were successfully prepared using electrohydrodynamic atomization (EHDA). The configuration was varied to control the distribution of CDDP within the particles, and high encapsulation efficiency (>70%) of the drug was achieved. NPs were produced with either a core–shell (CS) or a matrix (uniform) structure. It was shown that CS NPs had the most sustained release of the 2 formulations, demonstrating a slower linear release post initial “burst” and longer duration. The role of particle architecture on the rate of drug release in vitro was confirmed by fitting the experimental data with various kinetic models. This indicated that the release process was a simple diffusion mechanism. The CS NPs were effectively internalized into the endolysosomal compartments of cancer cells and demonstrated an increased cytotoxic efficacy (concentration of a drug that gives half maximal response [EC 50 ] reaching 6.2 µM) compared to free drug (EC 50 =9 µM) and uniform CDDP-distributed NPs (EC 50 =7.6 µM) in vitro. Thus, these experiments indicate that engineering the structure of PLGA NPs can be exploited to control both the dosage and the release characteristics for improved clinical chemotherapy treatment.

Cisplatin forms the basis for many chemotherapy regimens, however the maximum permissible dose is limited by its systemic toxicity. Nanoencapsulation of drugs has been shown to reduce off-target side effects and can potentially improve treatment burden on patients. However, uptake of nanoformulations at tumor sites is minimal without some form of active delivery. We have developed a submicron, polymeric nanoparticle based on biocompatible and degradable poly(lactic-co-glycolic acid) (PLGA) capable of encapsulating cisplatin and which can be bound to the surface of a phospholipid coated microbubble. The acoustic behavior and stability of the resulting nanoparticle loaded microbubbles will be compared with those of unloaded microbubbles. Results will also be presented on the extravasation of particles in a tissue mimicking phantom using a novel long working distance confocal microscope that enables particle distributions to be measured in situ and in real time.

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