Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Pharm Res. 2016 Dec;33(12):3057-3071. doi: 10.1007/s11095-016-2030-1. Epub 2016 Sep 6.
A delayed release bio-polymeric Dual-Biotic system has been extensively evaluated in this study to overcome the therapeutic issue of probiotic killing due to incorrect administration with the antibiotic.
In vitro and ex vivo release and characterization studies have been undertaken on the Dual-Biotic system. In vivo analyses utilizing a Large White pig model were also performed with commercial products used as a comparison. Intestinal fluid for probiotic quantification was aspirated using a surgically implanted intestinal cannula with Lactobacillus acidophilus cell counts determined through luminescence and inoculation onto Lactobacilli-specific agar. Plasma amoxicillin concentrations were determined through Ultra-Performance Liquid Chromatography. The reactional profile and crosslinking mechanism of ovalbumin and genipin was elucidated using molecular mechanic energy relationships in a vacuum system by exploring the spatial disposition of different concentrations of genipin with respect to ovalbumin with ovalbumin/genipin ratios of 1:1, 1:5 and 1:10.
In vivo evaluation of the Dual-Biotic system detailed maximum Lactobacillus viability (~455% baseline viability) 6 h after oral administration. Concurrent administration of the commercial products revealed a 75% decrease in bacterial viability when compared to the controls analyzed. A level A in vitro-in vivo correlation was also established with 96.9% predictability of amoxicillin release ascertained. The computational results achieved corroborated well with the experimental findings and physicochemical data.
Evaluation and correlation of the Dual-Biotic system has detailed the success of the formulation for the concurrent delivery of an antibiotic and probiotic.
本研究广泛评估了一种延迟释放的生物聚合物双重生物系统，以克服由于与抗生素一起使用而导致益生菌失活的治疗问题。
对双重生物系统进行了体外和离体释放及特性研究。还利用商业产品作为比较，对大型白猪模型进行了体内分析。利用手术植入的肠套管抽吸用于益生菌定量的肠液，通过发光和接种到乳杆菌特异性琼脂上测定嗜酸乳杆菌细胞计数。通过超高效液相色谱法测定血浆中阿莫西林的浓度。使用真空系统中的分子力学能量关系阐明卵清蛋白和京尼平的反应性和交联机制，通过探索不同浓度的京尼平相对于卵清蛋白的空间分布，研究卵清蛋白/京尼平比例为 1:1、1:5 和 1:10 时的反应性和交联机制。
对双重生物系统的体内评估详细说明了口服后 6 小时内最大乳酸杆菌活力（~455%基线活力）。与对照相比，同时给予商业产品会导致细菌活力下降 75%。还建立了体外-体内相关性水平 A，确定了阿莫西林释放的 96.9%预测性。计算结果与实验结果和物理化学数据吻合良好。
对双重生物系统的评估和相关性详细说明了该制剂成功地同时递送抗生素和益生菌。
