Pharmacokinetics of Free Oxytetracycline and Oxytetracycline Loaded Cockle Shell Calcium Carbonate-Based Nanoparticle in BALB/c Mice.

Sherifat Banke Idris,Jesse F F Abdullah,Siti-Zubaidah Ramanoon,Md Zuki Z A Abubakar,Muhammad Abdul Basit,Arifah Abdul Kadir

doi:10.3389/fvets.2020.00270

Abstract

The development and utilization of nano-antibiotics is currently gaining attention as a possible solution to antibiotic resistance. The aim of this study was therefore to determine the pharmacokinetics of free oxytetracycline (OTC) and oxytetracycline loaded cockle shell calcium carbonate-based nanoparticle (OTC-CNP) after a single dose of intraperitoneal (IP) administration in BALB/c mice. A total of 100 female BALB/c mice divided into two groups of equal number (n = 50) were administered with 10 mg/kg OTC and OTC-CNP, respectively. Blood samples were collected before and post-administration from both groups at time 0, 5, 10, 15, and 30 min and 1, 2, 6, 24, and 48 h, and OTC plasma concentration was quantified using a validated HPLC-UV method. The pharmacokinetic parameters were analyzed using a non-compartment model. The Cmax values of OTC in OTC-CNP and free OTC treated group were 64.99 and 23.53 μg/ml, respectively. OTC was detected up to 24 h in the OTC-CNP group as against 1 h in the free OTC group following intraperitoneal administration. In the OTC-CNP group, the plasma elimination rate of OTC was slower while the half-life, the area under the curve, and the volume of the distribution were increased. In conclusion, the pharmacokinetic profile of OTC in the OTC-CNP group differs significantly from that of free OTC. However, further studies are necessary to determine the antibacterial efficacy of OTC-CNP for the treatment of bacterial diseases.

Highlights

Oxytetracycline (OTC) is one of the frequently used antibiotics in livestock production [1]
Previous studies have shown that tetracyclines could be stably loaded and released from calcium-based nanoparticles [4, 6, 7] and overcome the efflux pump antibiotic resistance mechanism of Shigella flexineri when loaded into calcium phosphate nanoparticles (CNPs) [4]
Calcium carbonate nanoparticles have unique liquid phase characteristics that enable them to be crystalline solids at pH 7.4 and disintegrate to form biocompatible non-toxic ions at lower pH [9]. This property has been exploited to fabricate drug carriers in conditions where reduced pH is important such as the micro acidic environments created by biofilms, a major resistance mechanism, in chronic bacterial disease conditions [10, 11]

Summary

Introduction

Oxytetracycline (OTC) is one of the frequently used antibiotics in livestock production [1]. Its broad spectrum of activity and low cost compared to other antibiotics favor its use among veterinarians This widespread use and misuse has resulted in resistance of bacterial pathogens to OTC [2]. Calcium carbonate nanoparticles have unique liquid phase characteristics that enable them to be crystalline (stable) solids at pH 7.4 and disintegrate to form biocompatible non-toxic ions at lower pH [9]. This property has been exploited to fabricate drug carriers in conditions where reduced pH is important such as the micro acidic environments created by biofilms, a major resistance mechanism, in chronic bacterial disease conditions [10, 11]. The lower pH of the microenvironment within the biofilm extra polysaccharide matrix is due to anaerobic glycolysis and ion transfer challenges favoring the acidic medium within it [7, 12]

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Results

Conclusion