Biology Reference
In-Depth Information
Chapter 6
Presence of Polyanions and Sputum of Patients with
Cystic Fibrosis
Misagh Alipour, Zacharias E. Suntres, Majed Halwani, Ali O. Azghani,
and Abdelwahab Omri
INTRODUCTION
To compare the effectiveness of liposomal tobramycin or polymyxin B against
Pseudomonas aeruginosa
in the cystic fibrosis (CF) sputum and its inhibition by com-
mon polyanionic components such as DNA, F-actin, lipopolysaccharides (LPS), and
lipoteichoic acid (LTA).
Liposomal formulations were prepared from a mixture of 1,2-dimyristoyl-sn-
glycero-3-phosphocholine (DMPC) or 1,2-dipalmitoyl-sn-glycero-3-phosphocholine
(DPPC), and cholesterol (Chol), respectively. Stability of the formulations in different
biological milieus and antibacterial activities compared to conventional forms in the
presence of the aforementioned inhibitory factors or CF sputum were evaluated.
The formulations were stable in all conditions tested with no signifi cant differ-
ences compared to the controls. Inhibition of antibiotic formulations by DNA/F-actin
and LPS/LTA was concentration dependent. The DNA/F-actin (1251,000 mg/l) and
LPS/LTA (1 to 1,000 mg/l) inhibited conventional tobramycin bioactivity, whereas,
liposome-entrapped tobramycin was inhibited at higher concentrationsDNA/F-actin
(5001,000 mg/l) and LPS/LTA (1001,000 mg/l). Neither polymyxin B formulation was
inactivated by DNA/F-actin, but LPS/LTA (11,000 mg/l) inhibited the drug in conven-
tional form completely and higher concentrations of the inhibitors (1001,000 mg/l)
was required to inhibit the liposome-entrapped polymyxin B. Co-incubation with in-
hibitory factors (1,000 mg/l) increased conventional (16-fold) and liposomal (4-fold)
tobramycin minimum bactericidal concentrations (MBCs), while both polymyxin B
formulations were inhibited 64-fold.
Liposome-entrapment reduced antibiotic inhibition up to 100-fold and the CFU of
endogenous
P. aeruginosa
in sputum by 4-fold compared to the conventional antibi-
otic, suggesting their potential applications in CF lung infections.
Chronic bronchial infections caused by opportunistic pathogens in the lower re-
spiratory tract are a major cause of health decline in the CF population [1]. These
recurrent infections are mainly due to gram-negative bacteria, with
P. aeruginosa
be-
ing the most common species isolated [2-4]. Bacterial infections lead to biofi lm for-
mation and host infl ammatory responses and the ultimate resistance to antibacterial
therapies results in increased morbidity and mortality [5-10]. Presently, prophylactic
