Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs
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Date
2023-03-10
Authors
Motiei, Marjan
Mišík, Ondrej
Thanh Huong, Truong
Lízal, František
Humpolíček, Petr
Sedlařík, Vladimír
Sáha, Petr
0000-0003-4683-5145Advisor
Referee
Mark
Journal Title
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Volume Title
Publisher
Springer Nature
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Abstract
In this study, novel Trojan particles were engineered for direct delivery of doxorubicin (DOX) and miR-34a as model drugs to the lungs to raise local drug concentration, decrease pulmonary clearance, increase lung drug deposition, reduce systemic side effects, and overcome multi-drug resistance. For this purpose, targeted polyelectrolyte nanoparticles (tPENs) developed with layer-by-layer polymers (i.e., chitosan, dextran sulfate, and mannose-g-polyethyleneimine) were spray dried into a multiple-excipient (i.e., chitosan, leucine, and mannitol). The resulting nanoparticles were first characterized in terms of size, morphology, in vitro DOX release, cellular internalization, and in vitro cytotoxicity. tPENs showed comparable cellular uptake levels to PENs in A549 cells and no significant cytotoxicity on their metabolic activity. Co-loaded DOX/miR-34a showed a greater cytotoxicity effect than DOX-loaded tPENs and free drugs, which was confirmed by Actin staining. Thereafter, nano-in-microparticles were studied through size, morphology, aerosolization efficiency, residual moisture content, and in vitro DOX release. It was demonstrated that tPENs were successfully incorporated into microspheres with adequate emitted dose and fine particle fraction but low mass median aerodynamic diameter for deposition into the deep lung. The dry powder formulations also demonstrated a sustained DOX release at both pH values of 6.8 and 7.4.
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Citation
Discover nano. 2023, vol. 18, issue 1, p. 1-16.
https://link.springer.com/article/10.1186/s11671-023-03781-0
https://link.springer.com/article/10.1186/s11671-023-03781-0
Document type
Peer-reviewed
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en