Abstract

Some peptides demonstrate significant biological or antibacterial therapeutic effects. However, their effectiveness is limited by poor stability, susceptibility to enzymatic degradation and restricted membrane permeability. This study evaluates niosomal drug delivery systems as nanocarrier platforms for three representative peptides: vancomycin hydrochloride, nisin and insulin. The aim of this study is to improve peptide stability, achieve controlled release, and facilitate non-invasive administration via the oral cavity.

Niosomes were synthesized through a microfluidic method by using different non-ionic surfactants, including Span 40, Span 60 and Span 65, that combined with cholesterol and co-surfactants such as Kolliphor RH40, Kolliphor ELP, and Solutol HS15. The microfluidic method produced nanosized vesicles with diameters ranging from 100 to 300 nanometers, exhibiting narrow polydispersity and high encapsulation efficiency. Dynamic light scattering (DLS) confirmed particle size and uniformity. Peptide quantification was accomplished using high-performance liquid chromatography (HPLC) and the bicinchoninic acid (BCA) assay.

The optimised niosomal formulations of vancomycin and nisin were incorporated into polyvinyl alcohol (PVA) polymer as a film former base of fast-disintegrating oral films. These films were assessed for mechanical strength, flexibility, thickness, surface pH, and disintegration time. Results indicate rapid disintegration time and consistent film performances. In addition, agar diffusion assays confirmed the release of active peptide after niosomes formulation, as evidenced by clear inhibition zones against Bacillus subtilis. Analytical techniques, including Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM) have been employed to verify drug to excipient compatibility, thermal stability and homogeneous surface morphology.

Insulin-loaded niosomes were produced via microfluidic mixing using various Span surfactants and co-surfactants. Insulin niosomal formulation was intended for oral cavity administration in two dosage forms: microneedle films and the lyophilised buccal tablets. Optimised niosomal dispersion was freeze-dried with different lyoprotectants (mannitol, trehalose, glycine, sucrose). The most stable composition showed minimal nanoparticle size change and intact vesicle morphology using fluorescence microscope. Tablet characterization showed acceptable hardness, friability, and uniform insulin content after the tableting process. In vitro release studies using dialysis bags and permeability studies using Copley Franz cells equipped with polycarbonate membranes revealed controlled vancomycin, nisin and insulin release and enhanced drug diffusion rate over 24 hours compared to free peptides.

These results confirm that niosomal encapsulation can protect peptides from degradation and support controlled transmucosal delivery through the oral cavity.

Overall, this research demonstrates that niosomes function as stable and adaptable nanocarriers for peptide-based therapeutics. The integration of microfluidic fabrication, film casting or tablet compression technologies provides a simple and non-invasive platform to improve the stability, permeability and bioavailability of peptides.