A Dual-Biotic System for the Concurrent Delivery of Antibiotics and Probiotics: In Vitro, Ex Vivo, In Vivo and In Silico Evaluation and Correlation.
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.
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.
Mershen
M
Govender
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.
Yahya E
YE
Choonara
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.
Sandy
S
van Vuuren
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.
Pradeep
P
Kumar
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.
Lisa C
LC
du Toit
School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown, 2193, South Africa.
Kennedy
K
Erlwanger
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. viness.pillay@wits.ac.za.
Viness
V
Pillay
D000284:Administration, Oral; D000658:Amoxicillin / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003198:Computer Simulation; D003432:Cross-Linking Reagents / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D007413:Intestinal Mucosa / Q000378:metabolism; D039823:Iridoids / Q000737:chemistry; D007779:Lactobacillus acidophilus; D050296:Microbial Viability; D062105:Molecular Docking Simulation; D010047:Ovalbumin / Q000737:chemistry; D019936:Probiotics / Q000008:administration & dosage* / Q000737:chemistry; D034421:Sus scrofa
D000900:Anti-Bacterial Agents; D003432:Cross-Linking Reagents; D039823:Iridoids; D000658:Amoxicillin; D010047:Ovalbumin; C007834:genipin
Large White pig; concurrent oral antibiotic; in vitro; in vivo; molecular simulation; probiotic delivery