Evaluation of the anticandidal activity of clotrimazole using Lactobacillus caseie ghosts as biological drug carrier

以干酪乳杆菌菌体为生物药物载体评价克霉唑的抗念珠菌活性

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Abstract

BACKGROUND: Candida albicans cause oral and vaginal mucosa infections as well as bloodstream and deep-tissue infections. Commonly, clotrimazole as a broad-spectrum antimitotic drug applied for treatment of Candida albicans infections. Bacterial ghosts are dead cells that have the broad potential to target the various body tissues and cells as drug vector. OBJECTIVES: We hope to conquest this resistance by using clotrimazole loaded on bacterial ghosts. METHODS: Lactobacillus ghosts were produced by using tween 80 and lactic acid according to the protocol and the amount of the DNA and protein in supernatant was measured by Nano-drop spectrophotometry. Ghost's morphological characteristics were detected by using light microscopy, SEM and AFM. Antifungal activities of the synthesized ghosts were measured by plate methods. Three independent vertical Franz cells were used to evaluate drug release profile. BG-clotrimazole was added into cream base and was examined for dispensability as well as uniformity of the formulation on the skin. RESULTS: Results of the Nano-drop analysis showed that protein and DNA was seen in supernatant of treatment compared to control groups. AFM results showed well-dispersed and rod-shaped L. casei ghost cells. Lysis pores formation in the L. casei ghosts was indicated by SEM micrographs. BGs represent an excellent drug delivery system because of the high loading capability. Nearly, 50% of clotrimazole was released from BGs during 90 min. Highest anticandidal activity occurred using 100 mg/l clotrimazole-BG, while toxic effects were also seen with 10 mg/l clotrimazole. IC(50) clotrimazole-BG was found at 0.001 mg/l. Chemical stability results showed that about 90% of clotrimazole remained in the formulation. CONCLUSION: It could be concluded that the bacterial ghosts are very talented to high loading capability, keeping and releasing drug during six months, therefore these could act as an excellent drug delivery system.

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