Saba Al-Obaidy started her PhD project in Paunov Research Group at the Department of Chemistry of the University of Hull in April 2014. She graduated with a PhD degree in April 2018. Currently working as a Lecturer at Babylon University, Iraq. PhD supervisors: Prof. Vesselin N. Paunov (Co-PI) and Prof Gillian Greenway (PI)

Research project 1:

Boosting the antimicrobial action of Vancomycin and Berberine formulated in shellac nanoparticles of dual-surface functionality

We report a strong amplification of the antimicrobial action of vancomycin (VCM) or Berberine (BRB) encapsulated in shellac nanoparticles (NPs) with dual surface functionalisation [1,2]. These shellac nanocarriers for VCM were produced in  two steps: (i) a pH drop from aqueous ammonium shellac solution containing Poloxamer 407 (P407) as a steric stabilising polymer in solution of vancomycin hydrochloride, and (ii) subsequent doping with the insoluble cationic surfactant octadecylthrimethylammonium bromide (ODTAB) though a solvent change to yield cationic surface functionality.

Figure 1. Schematics of the two step process for the preparation of dual functionalised shellac nanocarriers for vancomycin (VCM). The VCM-loaded shellac NPs are sterically stabilised with Poloxamer 407 (P407) and have cationic surface functionality achieved by subsequent doping with the cationic surfactant octadecyltrimethyl ammonium bromide (ODTAB).

We evaluated the encapsulation efficiency of VCM and its release profiles from these nanocarriers. This study explored the antibiotic action of these VCM nanocarriers at the various stages of their preparation which helped us to evaluate how they could be made to work efficiently, to adapt their design and demonstrate the role of the nanocarrier dual functionalisation on its antibiotic action and delivery. The antibiotic effect of VCM loaded in such versatile functionalised shellac nanocarriers was tested on three different proxy microorganisms, C. reinhardtii, S. cerevisiae and E. coli. We also compared the antibiotic effect of free VCM with non-coated VCM-loaded nanocarriers at the same overall concentrations. The ODTAB coating of the shellac NPs strongly enhanced the antibiotic action of the encapsulated VCM across all tested microorganisms. The enhanced VCM action is explained with the increased electrostatic adhesion between the ODTAB-coated VCM-loaded shellac NPs and the negatively charged surface of the microbial cell walls which allows local delivery of VCM with a high concentration directly on the cell membrane [1]. We obtained very similar results for BRB which is another natural antimicrobial [2]. This nanocarrier-mediated boost of the antibiotic action may potentially breathe new life into old antibiotics and help to fight off antibiotic resistance by making them more effective.

Figure 2: (A) The antibacterial activity of different concentrations of VCM-loaded shellac NPs coated with ODTAB against E.coli. These solutions were prepared from 0.03 wt.% VCM loaded shellac NPs coated with 0.05 wt.% ODTAB as stock solution. (B) The relative luminescence unit representing the E.coli viability upon incubation with 0.01 wt.% VCM loaded in shellac NPs coated with 0.014 wt.% ODTAB in comparison with the antibacterial activity of free VCM and VCM-loaded shellac NPs and the cytotoxic effect of ODTAB-coated shellac NPs. The incubation was also achieved through incubating each concentration with a fixed amount of E.coli at pH 5.5. The data on (A) and (B) represent the luminance of the samples after treatment with BacTiter-Gloä reagent which is proportional to the concentration of viable bacteria (C)-(F) SEM images of E. coli cells whereby (C) represent the control sample, (D)-(F) E.coli incubated with 0.01 wt.% VCM-loaded in shellac NPs coated with 0.014 wt. % ODTAB after 2 h of incubation.

References

1. Al-Obaidy, S.S.M., Halbus, A.F., Greenway, G.M., Paunov, V.N., Boosting the antimicrobial action of vancomycin formulated in shellac nanoparticles of dual-surface functionality, J. Mater. Chem. B,  7 (2019) 3119-3133.
2. Al-Obaidy, S.S.M., Greenway, G.M., Paunov, V.N., Dual-functionalised shellac nanocarriers give a super-boost of the antimicrobial action of berberine, Nanoscale Advances, 1 (2019) 858–872. [Highlighted in Editors’ Hot Picks]