Cationic nanocapsule suspension as an alternative to the sublingual delivery of nifedipine

Abstract

Nifedipine (NIFE) is a calcium channel blocker drug used to treat cardiovascular diseases, angina, and hypertension. However, NIFE is photolabile, has a short biological half-life, low aqueous solubility, and undergoes an intense first-pass effect, compromising its oral bioavailability. Thus, this study aimed to develop NIFE-loaded nanocapsules for sublingual administration. Nanocapsule suspensions of Eudragit^® RS100 and medium chain triglycerides containing NIFE were prepared by the interfacial deposition of preformed polymer technique. The developed formulations showed particle size around 170 nm, polydispersity index below 0.2, positive zeta potential, and acid pH. The NIFE content was 0.98 ± 0.03 mg/mL, and the encapsulation efficiency was 99.9%. The natural light photodegradation experiment showed that the nanocapsules were able to provide NIFE photoprotection. The nanocapsules reduced the cytotoxicity of NIFE and showed no genotoxic effects in the Allium cepa model. Through the HET-CAM test, the formulations were classified as non-irritating. The developed nanocapsule suspension demonstrated a controlled release of NIFE and mucoadhesive potential. The in vitro permeation assay showed that the nanocapsules favored the NIFE permeation to the receptor compartment. In addition, the nanocapsules provided greater drug retention in the mucosa. Thus, the development of polymeric nanocapsule suspensions showed that this system could be a promising platform for NIFE sublingual administration.

Keywords:

• Nanoparticles
• Eudragit^®RS100
• sublingual permeation
• nifedipine
• controlled release

Acknowledgements

Bárbara Felin Osmari thanks to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-BR) for the financial support (masters fellowship, process number: 88887.490212/2020-00). Letícia Cruz thanks CNPq for PQ fellowship (process number: 315612/2020-7). The authors wish to thank Cristiane de Bona da Silva for Zetasizer access.

Author contributions

Bárbara Felin Osmari: methodology, conceptualization, investigation, formal analysis, visualization, and writing – original draft. Giovana Aime Medeiros: methodology, conceptualization, investigation, and visualization. Jéssica Brandão Reolon: methodology, investigation, and formal analysis. Vinícius Costa Prado: investigation and formal analysis. Natália Brucker: supervision and visualization. Letícia Cruz: conceptualization, supervision, visualization, writing – review and editing, and project administration.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Bárbara Felin Osmari thanks to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-BR) for the financial support [masters fellowship, process number: 88887.490212/2020-00]. Letícia Cruz thanks CNPq for PQ fellowship [process number: 315612/2020-7].