Solubilization of negatively charged DPPC/DPPG liposomes by bile salts

Hildebrand, Annegret; Beyer, Katja; Neubert, R.; Garidel, Patrick; Blume, Alfred

doi:10.1016/j.jcis.2004.06.085

Cited by 62 publications

(46 citation statements)

References 28 publications

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“…The phase diagrams for the vesicle-to-micelle transition in water ( Figure 7) are characterised by non-linear phase boundaries with a decrease of the phase boundaries at low lipid concentration [59,62,75,81]. This is not observed to such an extent for the lipid to bile salt systems dispersed in 100 mM NaCl.…”

Section: Total Detergent Concentration D T / Mmmentioning

confidence: 95%

“…for POPC and DPPC molecule A L ≈65 Å 2 ) [61,62] and A D the average bile salt molecular surface area (A D ≈40 Å 2 ) [56,62].…”

Section: Investigation Of Detergent Water To Membrane Partitioning Bymentioning

confidence: 99%

“…The thermodynamic parameters ΔG T # and TΔS T # are calculated for the intrinsic partition coefficient P 0 and the average partition coefficient P av [41,56,62,64,65].…”

Section: Investigation Of Detergent Water To Membrane Partitioning Bymentioning

confidence: 99%

“…Higher P av values and larger ΔG av T are obtained in 100 mM NaCl compared to pure water. The intrinsic partition coefficient should be unaffected by changing the ionic strength, due to the fact that charge screening effects at infinite dilution of the bile salt in the lipid phase is strongly reduced (for more details see [41,56,59,62]). …”

Section: Influence Of Ionic Strengthmentioning

confidence: 99%

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Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

et al. 2007

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Abstract:The two main steps of the membranolytic activity of detergents: 1) the partitioning of detergent molecules in the membrane and 2) the solubilisation of the membrane are systematically investigated. The interactions of two bile salt molecules, sodium cholate (NaC) and sodium deoxycholate (NaDC) with biological phospholipid model membranes are considered. The membranolytic activity is analysed as a function of the hydrophobicity of the bile salt, ionic strength, temperature, membrane phase properties, membrane surface charge and composition of the acyl chains of the lipids. The results are derived from calorimetric measurements (ITC, isothermal titration calorimetry). A thermodynamic model is described, taking into consideration electrostatic interactions, which is used for the calculation of the partition coefficient as well as to derive the complete thermodynamic parameters describing the interaction of detergents with biological membranes (change in enthalpy, change in free energy, change in entropy etc). The solubilisation properties are described in a so-called vesicle-to-micelle phase transition diagram. The obtained results are supplemented and confirmed by data obtained from other biophysical techniques (DSC differential scanning calorimetry, DLS dynamic light scattering, SANS small angle neutron scattering).

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Section: Total Detergent Concentration D T / Mmmentioning

confidence: 95%

“…for POPC and DPPC molecule A L ≈65 Å 2 ) [61,62] and A D the average bile salt molecular surface area (A D ≈40 Å 2 ) [56,62].…”

Section: Investigation Of Detergent Water To Membrane Partitioning Bymentioning

confidence: 99%

“…The thermodynamic parameters ΔG T # and TΔS T # are calculated for the intrinsic partition coefficient P 0 and the average partition coefficient P av [41,56,62,64,65].…”

Section: Investigation Of Detergent Water To Membrane Partitioning Bymentioning

confidence: 99%

Section: Influence Of Ionic Strengthmentioning

confidence: 99%

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Membranolytic Activity of Bile Salts: Influence of Biological Membrane Properties and Composition

et al. 2007

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“…It was shown that BS significantly enhances the intestinal permeability of CEF and increasing the absorption rate up to 2-times (32). However, the harsh environment in the GIT has negative impact on the oral administration as the presence of physiological BS leads to solubilization of the lipid bilayer (33)(34). The incorporation of BS enhancing the bioavailability of insulin colloidal drug carrier system has previously been reported (35)(36).…”

Section: Introductionmentioning

confidence: 99%

Nanosized Liposomes Containing Bile Salt: A Vesicular Nanocarrier for Enhancing Oral Bioavailability of BCS Class III Drug

et al. 2017

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-PURPOSE: Liposomes have been studied as a colloidal carrier in drug delivery systems, especially for oral administration. However, their low structural integrity in the gut is still a major shortcoming. Membrane disruptive effects of physiological bile salts in the small intestine result in premature drug release prior to intestinal absorption. Thus, we analyzed the stabilizing effect of sodium deoxycholate when incorporated into nano-sized liposomes. METHOD: Cefotaxime-loaded liposomes were prepared with different sodium deoxycholate concentrations (3.75-30 mM) by rotary film evaporation followed by nanosize reduction. The physical integrity of liposomes was evaluated by monitoring cefotaxime leakage, particle sizes in different simulated physiological media. The oral bioavailability and pharmacokinetics of cefotaxime was assessed in rats (n = 6 per group) after single dose of drug-encapsulated in liposomes containing bile salt, drug in conventional liposomes, and cefotaxime solution (oral and intravenous). RESULTS: Simulated gastric fluid with low pH showed less effect on the stability of liposomes in comparison to media containing physiological bile salts. Liposomes containing 15 mM sodium deoxycholate were most stable in size and retained the majority of encapsulated cefotaxime even in fed state of simulated intestinal fluid being the most destructive media. Pharmacokinetics data showed an increase in Cmax and AUC0-inf in the following order: cefotaxime solution < conventional liposomes < liposomes made with bile salts. The total oral bioavailability of cefotaxime in liposomes containing bile salt was found to be 5-times higher compared to cefotaxime solution and twice as much as in conventional liposomes. CONCLUSION: Incorporation of bile salts, initially used as membrane permeation enhancer, also acted as a stabilizer against physiological bile salts. The nanosized liposomes containing sodium deoxycholate were able to reduce the leakage of encapsulated cefotaxime in the gut due to the improved vesicle stability and to enhance the oral bioavailability of acid-labile drugs up to 5-fold.

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