Sustained delivery of olanzapine from sunflower oil-based polyol-urethane nanoparticles synthesised through a cyclic carbonate ring-opening reaction

Abstract

The forefront horizon of biomedical investigations in recent decades is parcelling-up and delivery of drugs to achieve controlled/targeted release. In this regard, developing green-based delivery systems for a spatiotemporal controlling therapeutic agent have drawn a lot of attention. A facile route based on cyclic carbonate ring-opening reaction has been utilised to synthesise a bio-based polyol-containing urethane bond [polyol-urethane (POU)] as a nanoparticulate drug delivery system of olanzapine in order to enhance its bioavailability. After characterisation, the nanoparticles were also estimated for in vitro release, toxicity, and pharmacokinetic studies. As olanzapine has shown poor bioavailability and permeability in the brain, the sustained release of olanzapine from the designed carriers could enhance pharmacokinetic effectiveness. POU in the aqueous solution formed micelles with a hydrophobic core and embedded olanzapine under the influence of its hydrophobic nature. Drug release from the nanoparticles (90 ± 0.43 nm in diameter) indicated a specific pattern with initial burst release, and then a sustained release behaviour (82 ± 3% after 168 h), by the Higuchi-based release mechanism. Pharmacokinetics assessments of POU-olanzapine nanoparticles were carried in male Wistar rats through intravenous administration. The obtained results paved a way to introduce the POU as an efficient platform to enhance the bioavailability of olanzapine in therapeutic methods.

Fig. 1

OZ chemical structure and its mechanism of action

Fig. 2

Synthesis route of POU (a) H₂ O₂ and formic acid, (b) CO₂, (c) Ethanol amine

Fig. 3

FTIR spectra of (a) SFO, (b) ESFO, (c) CSFO, (d) POU

Fig. 4

¹ HNMR of (a) SFO, (b) ESFO, (c) CSFO, (d) POU

Fig. 5

¹³ CNMR of (a) CSFO, (b) POU

Fig. 6

Thermal gravimetric analysis (a) Thermogram of POU, (b) X‐ray diffraction (XRD) of POU

Fig. 7

Fluorescence excitation spectra of pyrene in POU micelle solutions in different concentrations

Fig. 8

A scanning electron microscope (SEM) (a) Micrograph of OZ‐NPs, (b) Dynamic light scattering (DLS) of micrograph of OZ‐NPs, (c) Self‐assembly mechanism of OZ‐NPs

Fig. 9

SEM images of degraded OZ‐NPs (a) First day, (b) 2 days, (c) 4 days, (d) 7 days incubation in the phosphate buffer saline (pH 7.4), at 37°C

Fig. 10

Release profile of OZ from OZ‐NPs, data are shown as mean ± SD of three samples

Fig. 11

Model fit of the experimentally determined amounts of OZ‐NPs

Fig. 12

Comparison of cell viabilities upon 1‐, 3‐, and 7‐day incubation of cells in the extraction media of OZ‐NPs at four concentrations. Control groups are cells incubated in cell culture media

Fig. 13

Concentration–time curve of OZ‐NPs and OZ‐suspension

Fig. 14

Mechanism of OZ‐induced weight gain. Normal condition (upper), and OZ treated condition (lower)