Enhanced Antimicrobial Action of Chlorhexidine Loaded in Shellac Nanoparticles with Cationic Surface Functionality.

Saba S M Al-Obaidy,Gillian M Greenway,Vesselin N Paunov

doi:10.3390/pharmaceutics13091389

Saba S M Al-Obaidy, Gillian M Greenway + Show 1 more

Open Access

https://doi.org/10.3390/pharmaceutics13091389

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Abstract

We report on an active nanocarrier for chlorhexidine (CHX) based on sterically stabilized shellac nanoparticles (NPs) with dual surface functionalization, which greatly enhances the antimicrobial action of CHX. The fabrication process for the CHX nanocarrier is based on pH-induced co-precipitation of CHX-DG from an aqueous solution of ammonium shellac and Poloxamer 407 (P407), which serves as a steric stabilizing agent. This is followed by further surface modification with octadecyl trimethyl ammonium bromide (ODTAB) through a solvent change to yield cationic surface functionality. In this study, we assessed the encapsulation efficiency and release kinetics of the novel nanocarrier for CHX. We further examined the antimicrobial effects of the CHX nanocarriers and their individual components in order to gain better insight into how they work, to improve their design and to explore the impacts of their dual functionalization. The antimicrobial actions of CHX loaded in shellac NPs were examined on three different proxy microorganisms: a Gram-negative bacterium (E. coli), a yeast (S. cerevisiae) and a microalgae (C. reinhardtii). The antimicrobial actions of free CHX and CHX-loaded shellac NPs were compared over the same CHX concentration range. We found that the non-coated shellac NPs loaded with CHX showed inferior action compared with free CHX due to their negative surface charge; however, the ODTAB-coated, CHX-loaded shellac NPs strongly amplified the antimicrobial action of the CHX for the tested microorganisms. The enhancement of the CHX antimicrobial action was thought to be due to the increased electrostatic adhesion between the cationic surface of the ODTAB-coated, CHX-loaded shellac NPs and the anionic surface of the cell walls of the microorganisms, ensuring direct delivery of CHX with a high concentration locally on the cell membrane. The novel CHX nanocarriers with enhanced antimicrobial action may potentially find applications in dentistry for the development of more efficient formulations against conditions such as gingivitis, periodontitis and other oral infections, as well as enabling formulations to have lower CHX concentrations.

Highlights

CHX Encapsulation and Characterization of CHX Loaded within Shellac NPs
chlorhexidine di-gluconate (CHX-DG) was encapsulated within shellac NPs by mixing the three components shellac, Poloxamer 407 (P407) and chlorhexidine at pH 8, decreasing the pH to 5 to protonate the shellac carboxylic groups and to decrease their solubility so that they precipitated as nanoparticles
Our results show that the octadecyl trimethyl ammonium bromide (ODTAB) mainly affects the shellac NPs and causes their charge reversal

Summary

Introduction

Chlorhexidine (CHX) is a synthetic antimicrobial agent that is widely used in antiplaque and antigingivitic formulations for treatment of periodontitis due to its widespectrum action against both Gram-negative and Gram-positive bacteria, as well as in other applications against yeasts, fungi and some viruses. CHX release based on poly ε-caprolactone (PCL), with 200–300 nm CHX-loaded PCL capsules showing similar minimal inhibitory concentration to Staphylococcus epidermidis as Pharmaceutics 2021, 13, 1389. A single-emulsion-based solvent evaporation technique was used to fabricate microparticles with poly(dl-lacticco-glycolic acid), chlorhexidine di-gluconate and a linking complex of either methylatedβ-cyclodextrin or hydroxypropyl-β-cyclodextrin [5]. Seneviratne et al [6] reported on mesoporous silica nanoparticles encapsulated with pure chlorhexidine and investigated their antimicrobial properties on planktonic bacteria, mono-species and mixed-species models of oral biofilms.

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