Investigation of the antibacterial activity and efflux pump inhibitory effect of co-loaded piperine and gentamicin nanoliposomes in methicillin-resistant Staphylococcus aureus.
OBJECTIVE
Antibiotic resistance has stimulated the research for developing novel strategies that can prevent bacterial growth. Methicillin-resistant Staphylococcus aureus (MRSA), regarded as one of the most serious antibiotic-resistant bacteria which has been conventionally recognized as a nosocomial pathogen.


METHODS
Nanoliposomal formulations of piperine and gentamicin were prepared by dehydration-rehydration (DRV) method and characterized for size, zeta potential and encapsulation efficiency. Antibactericidal activities of liposomal and free forms were evaluated against MRSA ATCC 43300 by the determination of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and fractional inhibitory concentration index (FICI). The time-kill studies were carried out to evaluate the potency of antibacterial agents. The effect of piperine on bacterial efflux pumps was also investigated.


RESULTS
MIC values of gentamicin and piperine were 32 and 100 µg/mL, respectively. Synergetic effects were observed by the combination of gentamicin and piperine and FICI was determined to be 0.5. Following incorporation of gentamicin into liposomal gentamicin and liposomal combination, the MIC values were reduced 16- and 32-fold, respectively. MBC values of gentamicin reduced 4 and 8 times following incorporation into gentamicin and combination liposomes, respectively. In comparison with vancomycin, liposomal combination was more effective in bacterial inhibition and killing. Liposomal combination was the most effective preparations in time-kill study. Our findings indicated that liposomal piperine was able to inhibit the efflux pump sufficiently.


CONCLUSIONS
The results of this study revealed that liposomal combination is a powerful nano-antibacterial agent to eradicate MRSA infection. This dual-loaded formulation was an effective approach for eradication of MRSA.
Department of Food and Drug Control, Students Research Committee, Mashhad University of Medical Sciences , Mashhad , Iran .
Bahman
B
Khameneh
Milad
M
Iranshahy
Morteza
M
Ghandadi
Davod
D
Ghoochi Atashbeyk
Bibi Sedigheh
BS
Fazly Bazzaz
Mehrdad
M
Iranshahi
D000470:Alkaloids / Q000008:administration & dosage* / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology; D052117:Benzodioxoles / Q000008:administration & dosage* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods; D004357:Drug Synergism; D005839:Gentamicins / Q000008:administration & dosage* / Q000494:pharmacology; D008081:Liposomes; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles; D010316:Particle Size; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage* / Q000494:pharmacology
D000470:Alkaloids; D000900:Anti-Bacterial Agents; D052117:Benzodioxoles; D004338:Drug Combinations; D005839:Gentamicins; D008081:Liposomes; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine
Combination therapy; gentamicin; methicillin-resistant Staphylococcus aureus; microbial resistance; nanoliposomes; piperine; vancomycin