Korean J Physiol Pharmacol.  2024 May;28(3):275-284. 10.4196/kjpp.2024.28.3.275.

Development and assessment of nano drug delivery systems for combined delivery of rosuvastatin and ezetimibe

• Mohamed AM
• El-Zawahry EYI
• Ali MA
• Ibrahim DF
• Sabry SA
• Sarhan OM

• KMID: 2555669
• DOI: http://doi.org/10.4196/kjpp.2024.28.3.275

Abstract

Worldwide, cardiovascular disease is the main cause of death, which accordingly increased by hyperlipidemia. Hyperlipidemia therapy can include lifestyle changes and medications to control cholesterol levels. Statins are the medications of the first choice for dealing with lipid abnormalities. Rosuvastatin founds to control high lipid levels by hindering liver production of cholesterol and to achieve the targeted levels of low-density lipoprotein cholesterol, another lipid lowering agents named ezetimibe may be used as an added therapy. Both rosuvastatin and ezetimibe have low bioavailability which will stand as barrier to decrease cholesterol levels, because of such depictions, formulations of this combined therapy in nanotechnology will be of a great assistance. Our study demonstrated preparations of nanoparticles of this combined therapy, showing their physical characterizations, and examined their behavior in laboratory conditions and vivo habitation. The mean particle size was uniform, polydispersity index and zeta potential of formulations were found to be in the ranges of (0.181–0.72) and (–13.4 to –6.24), respectively. Acceptable limits of entrapment efficiency were affirmed with appearance of spherical and uniform nanoparticles. In vitro testing showed a sustained release of drug exceeded 90% over 24 h. In vivo study revealed an enhanced dissolution and bioavailability from loaded nanoparticles, which was evidenced by calculated pharmacokinetic parameters using triton for hyperlipidemia induction. Stability studies were performed and assured that the formulations are kept the same up to one month. Therefore, nano formulations is a suitable transporter for combined therapy of rosuvastatin and ezetimibe with improvement in their dissolution and bioavailability.

Keyword

Bioavailability; Cardiovascular disease; Poloxamer; Statins

Figure

• 

  Fig. 1 Loaded NPs shows a uniform size with suitable physical characterizations. Particle size and PDI (A); Zeta potential (B); transmission electron microscope (C) of rosuvastatin and ezetimibe encapsulated NPs. Each value represents the mean ± SD (n = 3). NP, nanoparticle; PDI, polydispersity index.

• 

  Fig. 2 F3 NPs showed enhanced dissolution rate in comparison to other formulations. In vitro release of (A) rosuvastatin and (B) ezetimibe from different nano-particles formulations. F1 to F4 are different formulations with different compositions of NPs. Each value represents the mean ± SD (n = 3). NPs, nanoparticles.

• 

  Fig. 3 Loaded NPs of ezetimibe and rosuvastatin showed better vivo release profile in comparison with their oral suspensions. In vivo release study of (A) rosuvastatin and (B) ezetimibe from different nano-particles formulations against drug suspension. Each value represents the mean ± SD (n = 6). All values in loaded NPs at each time were significantly different from those in drug suspension (p < 0.05). NPs, nanoparticles.

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