Enhanced bioavailability and antihypertensive activity of nisoldipine loaded nanoemulsion: optimization, cytotoxicity and uptake across Caco-2 cell line, pharmacokinetic and pharmacodynamic studies

Abstract

Objective: The present study explored the antihypertensive activity of nisoldipine in oil in water nanoemulsion to improve its oral bioavailability via intestinal lymphatic uptake.

Methods: Nanoemulsion was prepared by ultrasonication technique using Peceol, Cremophor EL and Transcutol HP as oil, surfactant and cosurfactant respectively. Optimization was done employing 3² full factorial design. The developed formulation was assessed for in vitro,cell line, ex vivo and in vivo studies.

Results: The experimental results indicated homogeneity of the nanoemulsion with globule size of 62.35 ± 2.55 nm and PDI value of 0.108 ± 0.01 with negative zeta potential (−26.2 ± 3.6 mV). Transmission electron microscopy showed spherical oil globules morphology. The in vitro diffusion study showed significant increase in drug release from NE formulations (98.51 ± 2.64%) as compared to plain drug dispersion (29.73 ± 2.15%) in 0.1 N HCl + 0.5% SLS medium. Moreover, higher quantitative and qualitative uptake of nanoemulsion via Caco-2 cells showed superior intestinal absorption and improved therapeutic activity of nisoldipine when compared to drug dispersion. Pharmacokinetic and pharmacodynamic study confirmed significantly (p ˂ 0.05) greater bioavailability and antihypertensive activity of nisoldipine nanoemulsion when compared to its dispersion. These results are visualized in abstract figure.

Conclusion: Thus, prepared nanoemulsion showed potential as oral delivery system for nisoldipine with superior oral bioavailability and therapeutic efficacy over drug dispersion.

Keywords:

• Antihypertensive activity
• Caco-2 cells
• bioavailability
• nanoemulsion
• cycloheximide
• pharmacodynamic

Acknowledgment

The authors would like to acknowledge University Grant Commission, India for providing the Research Fellowship in Science for Meritorious Student to Veenu Mundada; Technology Information, Forecasting and Assessment Council (TIFAC) - Center of Relevance & Excellence (CORE) in NDDS for providing research facilities; Alembic Research Center, India for providing Nisoldipine; BASF, India, and Gattefosse India Ltd, India for providing gift sample of Cremophor EL, Peceol and Transcutol HP respectively; Dr. Vikram Sarabhai Institute of Cell and Molecular Biology, The M.S. University of Baroda, India for providing facilities for cell uptake studies.

Disclosure statement

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