Publication detail

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

MOTIEI, M. MIŠÍK, O. THANH HUONG, T. LÍZAL, F. HUMPOLÍČEK, P. SEDLAŘÍK, V. SÁHA, P.

Original Title

Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs

Type

journal article in Web of Science

Language

English

Original 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.

Keywords

Nano-in-microparticles; Pulmonary delivery; Chitosan; Small molecules; miRNAs

Authors

MOTIEI, M.; MIŠÍK, O.; THANH HUONG, T.; LÍZAL, F.; HUMPOLÍČEK, P.; SEDLAŘÍK, V.; SÁHA, P.

Released

10. 3. 2023

Publisher

Springer Nature

Location

NEW YORK

ISBN

2731-9229

Periodical

Discover nano

Year of study

18

Number

1

State

United States of America

Pages from

1

Pages to

16

Pages count

16

URL

https://link.springer.com/article/10.1186/s11671-023-03781-0

Full text in the Digital Library

http://hdl.handle.net/11012/244720

BibTex

@article{BUT184894,
  author="Marjan {Motiei} and Ondrej {Mišík} and Truong {Thanh Huong} and František {Lízal} and Petr {Humpolíček} and Vladimír {Sedlařík} and Petr {Sáha}",
  title="Engineering of inhalable nano-in-microparticles for co-delivery of small molecules and miRNAs",
  journal="Discover nano",
  year="2023",
  volume="18",
  number="1",
  pages="16",
  doi="10.1186/s11671-023-03781-0",
  issn="2731-9229",
  url="https://link.springer.com/article/10.1186/s11671-023-03781-0"
}