What question did this study set out to answer?

The aim is to develop lipid-polymer hybrid nanoparticles for the dual delivery of rosuvastatin and ezetimibe.

April 13, 2026Open Access

Response0 surface guided design of lipid-polymer hybrid nanoparticles for dual delivery of rosuvastatin and ezetimibe

Key Points

The aim is to develop lipid-polymer hybrid nanoparticles for the dual delivery of rosuvastatin and ezetimibe.
Used nanoprecipitation to create hybrid nanoparticles.
Evaluated effects of lipid quantity, polymer type, and drug content using response surface methodology.
Characterized particle size, polydispersity index, and zeta potential.
Confirmed drug encapsulation and stability through various analytical techniques.
Achieved minimized particle size (229–240 nm) and polydispersity index (0.150–0.237).
Maximized total drug loading up to 7.44% with neutral zeta potential.
Demonstrated sustained drug release over 36 hours at physiological pH.
Nanoparticles exhibited spherical morphology and stability over three months.

Abstract

Fixed-dose formulations of rosuvastatin and ezetimibe loaded lipid-polymer hybrid nanoparticles were developed, employing a combination of polymer and lipid components designed to achieve a potential core-shell-like structure through nanoprecipitation method. For building structure, poly-(DL)-lactic-co-glycolic acid, acid-or ester-terminated, and soy phosphatidylcholine combined either with 1,2-dioleoyl-3-trimethylammonium-propane chloride or 1,2-distearoyl-sn-glycero-3-phosphoethanolamine as lipids were used along with α-hydro-ω-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer and polyoxyethylene (20) sorbitan monooleate as stabilizers. The effects of independent variables (lipid quantity and type, polymer type and total drugs quantity) on the response variables (particle size, polydispersity index, zeta potential, total drug loading and rosuvastatin to ezetimibe ratio) were evaluated using response surface methodology by Design-Expert® software. Four optimal formulations were developed, with acid-terminated polymer and 1,2-dioleoyl-3-trimethylammonium-propane chloride, minimized particle size (229–240 nm) and polydispersity index (0.150–0.237), maximized total drugs loading (up to 7.44%) and neutral zeta potential (within ± 10 mV), having successfully loaded rosuvastatin and ezetimibe in ratio of 1, 1.5, 2 and 2.5, with potential for its modulation based on lipid to polymer ratio. Optimal formulations with suitable biopharmaceutical and physicochemical properties for oral administration were obtained, showing sustained drugs release over 36 h (in pH 6.8 and 7.4) and stable colloidal behavior over three-month storage. SEM revealed spherical morphology and size consistent with DLS measurements. FTIR, DSC and TGA confirmed nanoparticles stability and gave valuable insight into the drug-excipient interactions. XRPD analysis confirmed drugs encapsulation in an amorphous state. The optimized formulations may serve as a promising platform for future development in hyperlipidemia therapy.

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