Niosomal encapsulation of the tuberculocidal drug rifampicin

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, 1:1]. For the negatively charged niosomes, the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 1:1:0.1] exhibited better percentage of entrapment viz., 35.08% compared to 30.64% for the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 4:2:1]. For the positively charged niosomes, the molar ratio [Span 60: Cholesterol: Stearylamine, 4:2:1] exhibited nearly similar entrapment viz., 53.83% compared to 52.80% for the molar ratio [Span 60: Cholesterol: Stearylamine, 1:1:0.1]. 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, 1:1] exhibited the least release values compared to molar ratio [Span 60: Cholesterol, 4:2]. For the negatively charged rifampicin niosomes, the molar ratio [Span 60: Cholesterol: Dicetylphosphate, 1:1:0.1] exhibited less release than [Span 60: Cholesterol: Dicetylphosphate, 4:2:1]. Determination of the tuberculocidal activity, of rifampicin niosomes compared to the free drug, in guinea pigs, is under way

Phytosomal encapsulation of a panax ginseng root extract for increasing its efficacy and safety

Phytosomes are complexes created when an herbal substance is combined with phosphatidylcholine. The new molecule is both water-soluble and fat-soluble, for greater bioavailability and absorption. Panax ginseng root extract is used as a tonic agent or an adaptogen that helps to improve overall health. Several pharmacological effects of P. ginseng has been investigated e.g. improvement of physical and mental performance, immune stimulation, liver protection and regulating glycaemia level. The main active components of P.ginseng are ginsenosides saponins. Ginsenosides Phytosomes were prepared using an aprotic solvent which is methylene chloride. Two types of ginsenosides phytosomes were prepared from L-alpha- phosphatidylcholine obtained from either egg yolk or soybean. Amount of complexed ginsenosides was estimated directly in the complex [phytosomes] using UV-visible recording spectrophotometer. The ratio of complexation between ginsenosides and lipids was 1:3 w/w. Dissolution rate profiles of the two types of phytosomes are nearly the same and they showed more sustained release of ginsenosides compared to the root extract; that can be explained by increased lipophilicity of ginsenosides by lipid complexation; denoting that the biological effect of ginsenosides phytosomes is expected to be maintained for longer time than that for the root extract. Characterization of phytosomes was carried out using Proton Nuclear Magnetic Resonance [[1]HNMR], Carbon Thirteen Nuclear Magnetic Resonance [[13]CNMR], Fourier Transform Infrared spectroscopy [FT-IR] and Differential Scanning Calorimetry [DSC]. All these characterization techniques have provided an evidence of complex formation. Ginsenosides phytosomes prepared using soybean L-alpha- phosphatidylcholine were biologically evaluated for enhancing the immunity against S.mansoni cercariae. Infected mice were divided at random into three groups; one as a control, the other two groups were administered the free drug [P.ginseng root extract] and the complexed drug [ginsenosides phytosomes] orally. Immunological response for the three groups was assessed by Enzyme Linked Immunosorbent Assay [ELISA] and worm and ova count in both liver and intestine. The results proved the promoted biological efficacy for the group administered phytosomes; due to increased lipophilicity of ginsenosides attained by complexation with phospholipids

Three months chemoprophylaxis of shistosomiasis using liposome encapsulated oxamniquine

Oxamniquine liposomes of the molar ratio 7:6, neutral and negatively charged, were prepared by the vortex dispersion method. Entrapped oxamniquine was estimated by HPLC analysis. Percentage drug encapsulated was found to range from 12.4% [neutral liposomes] to 20% [negative liposomes]. Drug-free and oxamniquine liposomes were characterized by particle-size analysis and Differential-scanning-calorimetry. Liver disposition of oxamniquine liposomes in mice, three-months post [s.c.] injection was investigated. Results reveal that oxamniquine liposomes are better liver-targeted than the free drug. Chemoprophylaxis of oxamniquine liposomes against S. mansoni in mice, was assessed for three months where drug liposomes displayed highly significant protection of 44%, unlike the free drug preparation; 1.3%. Stability study of oxamniquine liposomes was conducted on negative and neutral liposomes at -10, 4°, and 25°. Neutral liposomes displayed better sustained release of the drug over the negative ones. Storage at -10° provides more stable drug- liposomes. Sterilization of negatively charged oxamniquine liposomes was conducted employing four doses of gamma radiation of 10, 15, 20 and 25 KGy. Results revealed that 25 KGy is the optimum sterilizing dose, in addition to inferring high stability to the product

Optimising liposome-encapsulated praziquantel formulations for treating and overcoming resistant isolates of schistosoma mansoni

Praziquantel [pzq.] liposomes of [DPPC: Cholesterol] molar ratio 7:2, neutral [N] and negatively [-ve] charged, were prepared by the vortex dispersion method yielding multilamellar vesicles [MLV]. Some MLV were sonicated yielding unilamellar vesicles [ULV]. Entrapped pzq. was measured using UV spectrophotometric analysis at 265 nm. [N] UL and ML liposomes exhibited higher percentage entrapment over the [-ve] liposomes. Swelling at 52° for 24 hours, led to increased percentage entrapment of UL pzq. liposomes. Transmission electron micrographing was employed to characterize ML liposomes. [N] pzq. liposomes, of higher percentage entrapment, were used in curative and prophylactic experiments against susceptible [S] and resistant [R] isolates of S. mansoni, in mice. Pzq. liposomes were injected subcutaneously [s.c.] to effect efficient targeting to the site of infection viz., the liver. The effect of pzq. liposomes, in half dose, was compared to the same dose of free pzq, administered orally and as s.c. injection, in addition to full oral free pzq. [1000 mg/kg]. The curative experiment showed best efficacy for full oral free pzq. On the other hand, [N] pzq. ML liposomes imparted the highest 7-days chemoprophylactic effect against both [S] and [R] isolates of S. mansoni, emphasizing the significant success of such a pharmaceutical formulation in conquering the [R] S. mansoni isolate [EE2] responsible for evolving resistance to pzq. curative effect, in the Egyptian population

Effect of varying the pharmaceutical formulation on the biochemical a vailability and immunological behaviour of schistosomicidal drug, Oxamniquine

Oxamniquine [OXQ] is one of schistosomicide specific for Schistosoma mansoni [S. mansoni] infection. The aim of this work was to encapsulate OXQ into a liposome. These liposomal formulations in order to exhibit long term prophylactic effect against S. mansoni. It was found that OXQ exhibited marked chemoprophylaxis effect when encapsulated in negatively charged liposomes. Pharmacokinetically, OXQ liposomes are perfectly targeted to the liver whereby they release oxamniquine in minute amounts over extended periods in the proximate of schistosomules, maturing in liver sinusoids. All animal groups were injected with either free oxamniquine, OXQ free liposomes or OXQ liposomes encapsulated, one, two or three months before infection by S. mansoni cercariae and were sacrificed 6 weeks post infection. It was found that OXQ liposomes had moderate normalization effect on liver enzymes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and gamma glutamyl transferase in serum. Oxamniquine liposomes normalized A/G ratio and decreased the liver granuloma diameters. Infection increased the IgE and IgGl level, treatment with OXQ liposomes increased the level of IgG1 when given one or two months before infection, while free OXQ reduced IgG1 when given one month before infection and no significant change when given two months before infection. Treatment with different formulations to S. mansoni infected mice produced a significant decrease in IgE level after one and two months protection, while in normal animals there was an increase in IgG1 level after one month and no significant change after two months protection. So, it was concluded that OXQ in liposomal formulations is more efficient and safe than free drug in the protection against S. mansoni infection