Title:Enhanced Antibacterial Activity of Doxycycline and Rifampicin Combination
Loaded in Nanoparticles against Intracellular Brucella abortus
Volume: 19
Issue: 1
Author(s): Shilpa Dawre*, Padma V. Devarajan and Abdul Samad
Affiliation:
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM, NMIMS, Maharashtra
425405, India
Keywords:
Doxycycline-rifampicin combination therapy, nanoparticles, macrophages, Brucella abortus, brucellosis, scanning electron microscopy (SEM).
Abstract:
Introduction: Brucellosis is a zoonotic disease that is prevalent in livestock animals.
The bacteria reside inside the macrophage cells of the host. The WHO has endorseda combination
treatment therapy for brucellosis against the conventional monotherapy to avoid relapse and resistance.
Therefore, we developed nanoparticles incorporating doxycycline and rifampicin in combination.
Aim: The aim of the study is to develop polymeric nanoparticles incorporating doxycycline as well
as rifampicin and investigate the antibacterial activity of nanoparticles in U937 human macrophage
cells infected with B. abortus.
Methods: Polymeric nanoparticles were developed by the emulsion-solvent diffusion method, and
characterization was performed.
Results: The nanoparticles with high entrapment efficiency of both the drugs were developed successfully.
Scanning electron microscopy revealed a spherical morphology with a size ranging
~450nm, which can be easily engulfed by the macrophages. Zeta potential confirmed the colloidal
stability. Differential scanning calorimetry and X-ray diffraction suggested amorphization of doxycycline
and rifampicin in nanoparticles. Fourier transfer infrared spectroscopy could not confirm
the interaction of drugs with AOT. In vitro haemolysis study confirmed the safety of nanoparticles
(<10%) for IV administration. Further, nanoparticles revealed the sustained release of both drugs,
which followed diffusion kinetics. Nanoparticles were found stable for 6 months as per WHO
guidelines. The internalization study revealed nanoparticles could be easily uptaken by U-937 human
macrophage cells. The efficacy study demonstrated significantly high antibacterial activity of
nanoparticles as compared to free drug solution in U937 human macrophages cells infected with
Brucella abortus.
Conclusion: It can be concluded that the developed nanoparticles entrapping doxycycline and rifampicin
combination can be considered as a promising delivery system for enhancing the antibacterial
activity against Brucella abortus.