Abstract
The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route.
Highlights
Enhanced immunization strategies must be urgently found for tuberculosis control [1,2]
The formulation studies presented in this work aimed the optimization of the preparation conditions of bacille Calmette-Guérin (BCG)-loaded polymeric particles taking into consideration the final yield of production, encapsulation efficiency, particle size distribution and surface charge
The purpose of this study was to optimize the experimental parameters to prepare BCG-loaded polymeric microparticles intended for intranasal immunization studies, presenting suitable size distribution or surface charge, critical aspects for vaccine delivery
Summary
Enhanced immunization strategies must be urgently found for tuberculosis control [1,2]. The current available vaccine used for pre-exposure vaccination against tuberculosis is Mycobacterium bovis. As with most vaccines nowadays, BCG is parenterally administrated by subcutaneous route. This implies a relatively high production cost, the need for cold chain, and the need for trained personnel for vaccine administration, while it leads to lower patient compliance. Regarding the resulting immune response, parenterally delivered vaccines usually produce poor mucosal responses, which is critical to preventing tuberculosis, as Mycobacterium tuberculosis normally enters the host through mucosal surfaces. The nasal route might be an attractive alternative administration route [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
