Stenotrophomonas maltophilia (S. maltophilia), resistant to antibiotics, is a hazardous illness and a well-known worldwide public health issue. The present investigation included the preparation of formulations of tetracycline encapsulated in pullulan (referred to as HM-PULL-Tetracycline). The study aimed to assess the effectiveness of these formulations against strains of S. maltophilia in terms of their antimicrobial and anti-biofilm properties. The physicochemical characteristics of HM-PULL-Tetracycline were analyzed using a field scanning electron microscope, X-ray dispersion, Zeta potential, and dynamic light scattering analysis. The antibacterial and anti-biofilm activity was assessed using minimal biofilm inhibitory concentration and broth micro-dilution. In addition, the biocompatibility of HM-PULL-Tetracycline was assessed by investigating its cytotoxicity on the human diploid fibroblasts (HDF) normal cell line using the MTT test. The HM-PULL-Tetracycline formulation successfully prevented biofilm formation, measuring 179.7±2.66 nm in size and with an encapsulation efficiency of 84.86±3.14 %. It exhibited a biofilm growth inhibition rating of 69 % and significantly down-regulated the expression of the smf-1, rpfF, rmlA, and spgM biofilm genes in S. maltophilia strains (p<0.05). Furthermore, the HM-PULL-Tetracycline formulation exhibited a 4 to 6-fold increase in antibacterial efficacy compared to unbound tetracycline. The HM-PULL-Tetracycline formulation demonstrated cell viability of over 90 % at all doses tested against HDF normal cells. The findings of the current investigation demonstrate that HM-PULL-Tetracycline enhances the bactericidal and anti-biofilm properties without causing harm to healthy human cells. This suggests that Could be a promising approach for medication administration.
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