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Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan–Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study

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Abstract

Brucellosis is a common zoonotic infection, particularly in the developing world. The recommended treatment regimens for brucellosis involve the use of two medications such as doxycycline and curcumin in order to avoid relapses and prolonged use of these drugs. Doxycycline has excellent activity in the acidic phagolysosomal environment, while curcumin modulates the immune system function and macrophage activity. Due to the intracellular existence of Brucellae and the different anti-immune mechanisms of Brucella, the treatment of Brucella infection faces many limitations. The design of nanosystems is a promising treatment approach for brucellosis. The objective of this study was to design and evaluate the efficacy of in situ pH-responsive curcumin-loaded niosome hydrogel and doxycycline-loaded chitosan–sodium alginate nanoparticles as chemotherapeutic agents against brucellosis. The prepared formulae showed a spherical nano shape with a slow drug release pattern and small particle size. The prepared formulae were evaluated in vivo using Guinea pigs experimentally infected with Brucella melitensis biovar3. The prepared formula combination gave a significant high reduction rate of Brucella spleen viable count compared with that of untreated controls at p < 0.05. The results showed that the treatment schemes were not fully successful in eliminating Brucella infection in Guinea pigs; however, they significantly (p < 0.05) reduced the viable Brucella count in a shorter time and sub-therapeutic doses. Collectively the novel prepared formulae could be a successful therapy for the effective treatment of brucellosis infection at the recommended therapeutic doses.

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Abbreviations

DOX:

Doxycycline

LD50 :

Median lethal dose

GMO:

Glyceryl monooleate

b.wt:

Body weight

h:

Hour

IPB:

Isotonic phosphate buffer

EE:

Entrapment efficiency

PDI:

Polydispersity index

TEM:

Transmission electron microscopy

BPAT:

Buffered plate antigen test

RBT:

Rose Bengal test

BAPA:

Buffered acidified plate antigen

CFU:

Colony-forming unit

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Correspondence to Fatma I. Abo El-Ela.

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Abo El-Ela, F.I., Hussein, K.H., El-Banna, H.A. et al. Treatment of Brucellosis in Guinea Pigs via a Combination of Engineered Novel pH-Responsive Curcumin Niosome Hydrogel and Doxycycline-Loaded Chitosan–Sodium Alginate Nanoparticles: an In Vitro and In Vivo Study. AAPS PharmSciTech 21, 326 (2020). https://doi.org/10.1208/s12249-020-01833-7

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