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Drug Loading in Poly(butyl cyanoacrylate)-Based Polymeric Microbubbles
Mengjiao Liu1, Anshuman Dasgupta1, Patrick Koczera1,2
1Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, Aachen 52074, Germany.
Abstract:
Microbubbles (MB) are routinely used ultrasound (US) contrast agents that have recently attracted increasing attention as stimuli-responsive drug delivery systems. To better understand MB-based drug delivery, we studied the role of drug hydrophobicity and molecular weight on MB loading, shelf-life stability, US properties, and drug release. Eight model drugs, varying in hydrophobicity and molecular weight, were loaded into the shell of poly(butyl cyanoacrylate) (PBCA) MB. In the case of drugs with progesterone as a common structural backbone (i.e., for corticosteroids), loading capacity and drug release correlated well with hydrophobicity and molecular weight. Conversely, when employing drugs with no structural similarity (i.e., four different fluorescent dyes), loading capacity and release did not correlate with hydrophobicity and molecular weight. All model drug-loaded MB formulations could be equally efficiently destroyed upon exposure to US. Together, these findings provide valuable insights on how the physicochemical properties of (model) drug molecules affect their loading and retention in and US-induced release from polymeric MB, thereby facilitating the development of drug-loaded MB formulations for US-triggered drug delivery.
Insights
Microbubbles (MB) effectively deliver drugs, with loading and release influenced by drug properties like hydrophobicity and molecular weight, especially for similar drug structures. Ultrasound (US) efficiently destroys all MB formulations.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Ultrasound Technology
Background:
- Microbubbles (MB) are established ultrasound (US) contrast agents.
- MB are emerging as promising stimuli-responsive platforms for drug delivery.
- Understanding drug physicochemical properties is crucial for optimizing MB-based delivery.
Purpose of the Study:
- To investigate the impact of drug hydrophobicity and molecular weight on MB loading, stability, and release.
- To evaluate the influence of drug structural similarity on these parameters.
- To assess the US-triggered release efficiency across different drug-loaded MB formulations.
Main Methods:
- Loading of eight model drugs (varying in hydrophobicity and molecular weight) into poly(butyl cyanoacrylate) (PBCA) MB.
- Assessment of MB loading capacity, shelf-life stability, and US properties.
- Evaluation of drug release kinetics and US-induced MB destruction.
Main Results:
- For drugs with similar structures (corticosteroids), loading and release strongly correlated with hydrophobicity and molecular weight.
- For structurally dissimilar drugs (fluorescent dyes), no clear correlation was observed.
- All tested MB formulations exhibited efficient destruction upon US exposure.
Conclusions:
- Physicochemical properties, particularly hydrophobicity and molecular weight, significantly influence drug loading and retention in polymeric MB.
- Drug structural similarity plays a key role in predicting loading and release behavior.
- These findings are vital for designing effective ultrasound-triggered drug delivery systems using MB.
