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Anacardic acid encapsulated solid lipid nanoparticles for Staphylococcus aureus biofilm therapy: chitosan and DNase coating improves antimicrobial activity

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Abstract

Biofilm mediated bacterial infections are the key factors in the progression of infectious diseases due to the evolution of antimicrobial resistance. Traditional therapy involving antibiotics is not adequate enough for treatment of such infections due to the increased resistance triggered by biofilm. To overcome this challenge, we developed anacardic acid (Ana) loaded solid lipid nanoparticles (SLNs), further coated with chitosan and DNase (Ana-SLNs-CH-DNase). The DNase coating was hypothesized to degrade the e-DNA, while chitosan was coated to yield positively charged SLNs with additional adhesion to biofilms. The SLNs were developed using homogenization method and further evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Drug excipient compatibility was confirmed by using FT-IR study, while encapsulation of Ana in SLNs was confirmed by X-ray diffraction study. The SLNs demonstrated sustained release for up to 24 h and excellent stability at room temperature for up to 3 months. The developed SLNs were found non-toxic against human immortalized keratinocyte (HaCaT) cells while demonstrated remarkably higher antimicrobial efficacy against Staphylococcus aureus. Excellent effect of the developed SLNs on minimum biofilm inhibition concentration and minimum biofilm eradication concentration further confirmed the superiority of the developed formulation strategy. A significant (p < 0.05) reduction in biofilm thickness and biomass, as confirmed by confocal laser scanning microscopy, was observed in the case of developed SLNs in comparison with control. Cumulatively, the results suggest the enhanced efficacy of the developed formulation strategy to overcome the biofilm-mediated antimicrobial resistance.

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Acknowledgments

The authors acknowledge financial support from the Department of Science & Technology (DST), grant no: DST/SSTP/UP/2013-14/12TH PLAN/132, Government of India. The authors would also like to acknowledge the Central Instrument Facility Centre (CIFC), Indian Institute of Technology (Banaras Hindu University), Varanasi, for providing the instrument facilities

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, 221005, India

    Md Meraj Anjum, Krishna Kumar Patel, Deepa Dehari, Ashish Kumar Agrawal & Sanjay Singh

  2. Department of Microbiology, Institute of Medical Sciences (Banaras Hindu University), Varanasi, Uttar Pradesh, 221005, India

    Nidhi Pandey & Ragini Tilak

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  1. Md Meraj Anjum
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  2. Krishna Kumar Patel
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Correspondence to Ashish Kumar Agrawal or Sanjay Singh.

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Anjum, M.M., Patel, K.K., Dehari, D. et al. Anacardic acid encapsulated solid lipid nanoparticles for Staphylococcus aureus biofilm therapy: chitosan and DNase coating improves antimicrobial activity. Drug Deliv. and Transl. Res. 11, 305–317 (2021). https://doi.org/10.1007/s13346-020-00795-4

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