Niosomal encapsulation of the tuberculocidal drug rifampicin

ABSTRACT

Niosomes are vesicles formed by self-assembly of non-ionic surfactants that have potential applications in the delivery of hydrophobic and hydrophilic drugs intracellularly e.g. to macrophages and hence, are expected to increase the potency, safety and to overcome the resistant strains of M. tuberculosis. Rifampicin niosomes were prepared by the chloroform-film method using Span 60 and cholesterol. Stearylamine and dicetylphosphate were added as the positive and negative charge inducing agents, respectively. Characterization of Rifampicin niosomes was carried out using Differential Scanning Calorimetry [DSC] and Electron Microscopy. Computer presentations of DSC thermograms are provided for drug niosomes, drug free niosomes as well as the individual components of the niosomes investigated, using the Shimadzu-50 DS Calorimeter. Electron micrographs reveal the shape of the investigated niosomes. Rifampicin niosomes, thus prepared and characterized, were investigated for the purpose of optimizing the drug encapsulation efficiency, release profiles and expected increased potency and safety. The latter expectancy is explained by the intracellular targeting behavior of the drug niosomes compared to free drug. The results indicate that for rifampicin neutral niosomes, the molar ratio [Span 60 Cholesterol, 4 2] exhibited better percentage of entrapment viz., 36.55% compared to 26.98% for the molar ratio [Span 60 Cholesterol, 11]. For the negatively charged niosomes, the molar ratio [Span 60 Cholesterol Dicetylphosphate, 110.1] exhibited better percentage of entrapment viz., 35.08% compared to 30.64% for the molar ratio [Span 60 Cholesterol Dicetylphosphate, 421]. For the positively charged niosomes, the molar ratio [Span 60 Cholesterol Stearylamine, 421] exhibited nearly similar entrapment viz., 53.83% compared to 52.80% for the molar ratio [Span 60 Cholesterol Stearylamine, 110.1]. The release profiles of these rifampicin niosomes were performed at 37°C, as a trial to anticipate the expected behavior of these niosomes under the hydrodynamic stress of in-vivo conditions. The release profile values for the different niosomes investigated showed that neutral niosomes of molar ratio [Span 60 Cholesterol, 11] exhibited the least release values compared to molar ratio [Span 60 Cholesterol, 42]. For the negatively charged rifampicin niosomes, the molar ratio [Span 60 Cholesterol Dicetylphosphate, 110.1] exhibited less release than [Span 60 Cholesterol Dicetylphosphate, 421]. Determination of the tuberculocidal activity, of rifampicin niosomes compared to the free drug, in guinea pigs, is under way