BCS class II drug loaded protein nanoparticles with enhanced oral bioavailability: in vitro evaluation and in vivo pharmacokinetic study in rats.

The aim of the study was to improve the bioavailability of atorvastatin calcium (ATC) by formulating polymeric nanoparticles (NPs) with an easy and cost-effective approach. ATC entrapped gelatin nanoparticles (AEGNPs) were prepared by using a simple one-step desolvation method. The formed NPs were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Morphological study exhibited a homogenous spherical shape of formulated NPs. FTIR studies revealed the chemical compatibility of the drug with gelatin. The improvement in drug delivery kinetics of AEGNPs could be attributed to amorphization along with the reduction in particle size of ATC. The pharmacokinetic study in Sprague-Dawley rats revealed that the Cmax and AUC0-24 of AEGNPs in rats were ∼4-fold and ∼11-fold higher than that of pure ATC suspension. The research presented successfully shows that AEGNPs preparation by one-step desolvation, using minimum excipients is a quick, easy and reproducible method. These results suggest that the ATC encapsulated gelatin NP is a promising approach for the oral delivery of ATC, improving the bioavailability of the drug.

Optimisation of one-step desolvation and scale-up of gelatine nanoparticle production.

Gelatine nanoparticles (GNPs) are biodegradable and biocompatible drug delivery systems with excellent clinical performances. A two-step desolvation is commonly used for their preparation, although this methodology has several shortcomings: lack of reproducibility, small scales and low yields. A straightforward and more consistent GNP preparation approach is presented here focusing on the development of a one-step desolvation with the use of a commercially available gelatine type. Controlled stirring conditions and ultrafiltration are used to achieve large-scale production of nanoparticles of up to 2.6 g per batch. Particle size distributions are conserved and comparable to those determined for two-step desolvation on small scale. Additionally, a range of cross-linking agents is examined for their effectiveness in stabilising GNPs as an alternative to glutaraldehyde. Glyceraldehyde demonstrated outstanding properties, which led to high colloidal stability. This approach optimises the manufacturing process and the scale-up of the production capacity, providing a clear potential for future applications.