Dressing liposomal particles with chitosan and poly(vinylic alcohol) for oral vaccine delivery

Abstract

Liposomes have been used as adjuvants since 1974. One major limitation for the use of liposomes in oral vaccines is the lipid structure instability caused by enzyme activities. Our aim was to combine liposomes that could encapsulate antigens (i.e., Dtxd, diphtheria toxoid) with chitosan, which protects the particles and promotes mucoadhesibility. We employed physical techniques to understand the process by which liposomes (SPC: Cho, 3:1) can be sandwiched with chitosan (Chi) and stabilized by PVA (poly-vinylic alcohol), which are biodegradable, biocompatible polymers. Round, smooth-surfaced particles of REVs-Chi (reversed-phase vesicles sandwiched by Chi) stabilized by PVA were obtained. The REVs encapsulation efficiencies (Dtxd was used as the antigen) were directly dependent on the Chi and PVA present in the formulation. Chi adsorption on the REVs surface was accompanied by an increase of ζ-potential. In contrast, PVA adsorption on the REVs-Chi surface was accompanied by a decrease of ζ-potential. The presence of Dtxd increased the Chi surface-adsorption efficiency. The PVA affinity by mucine was 2,000 times higher than that observed with Chi alone and did not depend on the molecule being in solution or adsorbed on the liposomal surface. The liberation of encapsulated Dtxd was retarded by encapsulation within REVs-Chi-PVA. These results lead us to conclude that these new, stabilized particles were able to be adsorbed by intestinal surfaces, resisted degradation, and controlled antigen release. Therefore, REVs-Chi-PVA particles can be used as an oral delivery adjuvant.

Adapting liposomes for oral drug delivery

“…Furthermore, disulfide bridges form between thiolated polymers with cysteine-rich subdomains of mucus glycoproteins118., 134., as well as the interpenetration of polymers within mucus43., 92.. Mucins, a family of glycoproteins, have been generally used to evaluate the mucoadhesion of polymer-coated liposomes in vitro 116., 132., 170., as mucins are largely responsible for mucus viscoelastic and adhesive properties. There are ex vivo 42., 92., 118. and in vivo 132 models for this purpose.…”

Preparation, Optimization and Characterization of Bovine Lactoferrin‐loaded Liposomes and Solid Lipid Particles Modified by Hydrophilic Polymers Using Factorial Design

“…However, liposomes are prone to the combined degrading effects of the acidic pH of the stomach, bile salts and pancreatic lipases. To overcome these drawbacks, cross‐linking the liposomes with biopolymers such as pectin, alginate and chitosan could potentially prolong drug release and improve the pharmacological action by increasing mucoadhesiveness .…”

Delivery of immunogens to mucosal immune system using an oral inactivated cholera vaccine

“…11 One of the critical challenges related to such vehicles is the size of the vesicles. 12,13 Although some reports indicate that particles smaller than 10 μm can be taken up by M-cells of Peyer's patches, 14 there is no clear consensus in the scientific community regarding the optimal size for uptake by the gut mucosa and the M cells specifically. However, sizing is not the only obstacle with such oral vehicle delivery systems, the ratio and quantity of chemical components, the amount of encapsulated immunogens, the ionic surface charge, the type of associated adjuvants, and the dose of administration were also reported as other challenges.…”