Proliposome Technology for Protein Delivery
Growing attention has been given to the potential of the respiratory tract for systemic delivery of macromolecules, particularly proteins and peptides. However, limitations such as short transit time and loss of activity of some proteins and peptides in the respiratory tract need to be overcome. Consequently, the utility of controlled drug delivery systems such as liposomes as protein carriers appear promising. Unfortunately, liposomes are unstable in aqueous dispersions. Additionally, conventional liposome preparation methods such as the thin film hydration are difficult to scale-up, and also demonstrate low entrapment efficiencies for hydrophilic materials. The aim of this work was to develop novel submicron mucoadhesive liposomes entrapping the protein immunoglobulin g (IgG) using the proliposome method. Additionally, this work explored the potential of the generated liposomes for respiratory tract delivery via medical nebulisers and nasal sprays with different operating principles. Liposomes generated from the proliposome technology were multilamellar as cryo-TEM studies revealed. The generated liposomes were capable of entrapping considerable concentrations of salbutamol sulfate (59.1%), ovalbumin (43.3 %) and IgG (29.9 %). Also, the generated liposomes demonstrated superior entrapment efficiency of IgG to other liposome preparation methods (thin film and particulate- based proliposome technology). Reduction of liposome size to 400 nm and the incorporation of the mucoadhesive agent sodium alginate markedly enhanced the entrapment of IgG in liposomes (up to 50 %). The secondary structure and immunological reactivity of IgG were also maintained following its incorporation in liposomes as demonstrated by circular dichroism and microagglutination assay, respectively. Nebulisation was found to fragment liposomes as well as reduce the activity of the entrapped IgG. The degree of liposome fragmentation and loss of activity of IgG varied markedly among different medical nebulisers. Liposome size distribution and IgG immune reactivity studies elucidated that vibrating-mesh nebuliser was least disruptive to liposome structure and the immunoreactivity of the incorporated IgG was least affected following its use (retained activity of 83% versus 24% and 39% for the ultrasonic and air-jet nebulisers, respectively). Contrary to medical nebulizers, this work illustrated that all studied nasal devices preserved both the integrity of liposomes and the incorporated IgG. In conclusion, the findings of this study demonstrate potential benefits in drug delivery employing both intranasal administration and proliposome technology offer with great promise in using proliposome formulations for intranasal protein delivery.
Networked Digital Library of Theses and Dissertations