Synthesis and evaluation of chitosan-alginate microspheres loaded with various combinations of enrofloxacin and selected phytochemicals against pathogenic bacteria

T. Manuroop, K Bharavi, A. Jahan, M Alpharaj, P. A. Kumar, G. S. Rao
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Abstract

Enrofloxacin in combination with phytochemicals such as Curcumin (CUR), Piperin (PIP), Cinnamic acid (CIA), Caffeic acid (CAA) and Syringic acid (SYA) exhibits notable synergism against pathogenic bacteria. Chitosan-alginate encapsulated microspheres containing enrofloxacin and phytochemicals prepared and evaluated for their synergistic effect and reduction in individual agent’s disadvantages. CSALG microspheres were prepared by impregnating enrofloxacin (CS-ALG-EN) alone and in combination with respective phytochemicals such as CS-ALG-EN-CUR, CS-ALG-EN-PIP, CS-ALG-EN-CIA, CSALG-EN-CAA & CS-ALG-EN-SYA and evaluated for shape, size, loading efficacy, release kinetics of enrofloxacin and MIC of enrofloxacin along with various phytochemicals against MTCC and clinical isolate bacteria. Microspheres were spherical. When combined with phytochemicals the enrofloxacin loading efficacy decreased variably with respective phytochemicals. The % cumulative release of enrofloxacin from all microspheres was maximum at pH 1.2 and further increased at pH 6.8. CAA and SYA improved the release and CIA, CUR and PIP decreased the release of enrofloxacin from respective microspheres compared to CS-ALG-EN. The dissolution efficacy increased by addition of SYA, CAA while PIP, CIA and CUR decreased. The mean dissolution time is same in PIP, SYA, CAA while CIA showed lowest and CUR highest when compared with enrofloxacin alone loaded microspheres. The release of enrofloxacin followed korsmeyer-peppas model by following Fickian diffusion/Quasi-Fickian diffusion from spheres. The MIC of enrofloxacin significantly lowered in combination with CUR, PIP, CIA, CAA on both MTCC and clinical isolates of pathogenic bacteria. In conclusion chitosan-alginate encapsulation improved the bioavailability of enrofloxacin and phytochemicals and combination showed synergistic antibacterial effect.
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不同组合恩诺沙星及植物化学物质负载壳聚糖-海藻酸微球的合成及抑菌效果评价
恩诺沙星与姜黄素(CUR)、辣椒素(PIP)、肉桂酸(CIA)、咖啡酸(CAA)和丁香酸(SYA)等植物化学物质联用对致病菌具有显著的协同作用。制备了含有恩诺沙星和植物化学物质的壳聚糖-海藻酸盐包封微球,并对其协同效应和减少单个药物的缺点进行了评价。通过单独浸渍恩诺沙星(CS-ALG-EN)并与各自的植物化学物质CS-ALG-EN- cur、CS-ALG-EN- pip、CS-ALG-EN- cia、CS-ALG-EN- caa和CS-ALG-EN- sya共同浸渍制备CSALG微球,并对恩诺沙星的形状、大小、载药效果、释放动力学和恩诺沙星与各种植物化学物质对MTCC和临床分离菌的MIC进行了评价。微球是球形的。当与植物化学物质联合使用时,恩诺沙星的负载效率随植物化学物质的不同而不同。在pH值为1.2时,恩诺沙星的累积释放量最大,在pH值为6.8时进一步增加。与CS-ALG-EN相比,CAA和SYA提高了恩诺沙星微球的释放,CIA、CUR和PIP降低了恩诺沙星微球的释放。SYA、CAA的加入提高了溶出效果,而PIP、CIA和CUR的加入降低了溶出效果。与单独载恩诺沙星微球相比,PIP、SYA、CAA的平均溶出时间相同,CIA最低,CUR最高。恩诺沙星的释放符合korsmemeyer -peppas模型,从球体开始遵循Fickian扩散/准Fickian扩散。恩诺沙星联合CUR、PIP、CIA、CAA对MTCC和临床分离病原菌的MIC均显著降低。综上所述,壳聚糖-海藻酸盐包封提高了恩诺沙星与植物化学物质的生物利用度,并具有协同抑菌作用。
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