Liposomes for drug delivery to the lungs by nebulization

Zaru, Marco; Mourtas, Spyridon; Klepetsanis, Pavlos; Fadda, Anna Maria; Antimisiaris, Sophia G.

doi:10.1016/j.ejpb.2007.04.005

Cited by 117 publications

(61 citation statements)

References 31 publications

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“…To remove any possible structural defects, the obtained liposomes were left for 1 h at the above temperatures, i.e. above their transition temperature, which is 41°C for DPPC (Zaru et al 2009) and -18°C for DOPC (Lewis et al 1988). Thus prepared liposomes were kept in a fridge in dark place.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

“…All the lipid vesicles were prepared by a thin film hydration method (Dual et al 2012, Zaru et al 2009). A thin lipid film was formed by dissolving the lipid (DPPC or DOPC) in chloroform/methanol solution (2:1, v/v) in a round bottom flask and following removal of the solvent under vacuum condition (117 mbar, 24 h) at room temperature, which ensured complete removal of the solvents.…”

Section: Preparation Of Liposomesmentioning

confidence: 99%

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Zeta potential and surface charge of DPPC and DOPC liposomes in the presence of PLC enzyme

2016

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Zeta potential of liposomes is often measured in studies of their properties and/or applications. However, there are not many papers published in which zeta potential was determined during enzymatic reaction of a lipid. Therefore in this paper size, polydispersity index, and zeta potentials of 1,2-dipalmitoylsn-glycero-3-phosphatidylcholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) liposomes were investigated in 1 mM NaCl (pH 6.2) and phosphate buffer (pH 8.1) during 60 min of phospholipase C action at 20 and 37°C. The hydrocarbon chains saturation differ these two phospholipids what appears in some differences in the zeta potential changes during the hydrolysis reaction run. The polydispersity index of the liposomes indicates that they are relatively stable and monodisperse, except for DPPC in phosphate buffer where up to 30 % of the initial amount forms larger size moieties, possibly aggregates of the liposomes, enzyme and the hydrolysis products. However, in this buffer zeta potential of the liposomes practically does not change during PLC action. Also the changes of zeta potential of DOPC liposomes are minor, although their negative values are much smaller than those of DPPC at both temperatures. These small changes of the potential may be due to compression of the diffuse double layer by present phosphate buffer. However, distinct changes of the zeta potentials in the presence of PLC take place in NaCl solution. The observed changes can be explained by reorientation of the phospholipid polar heads and their different density on DPPC and DOPC surface of the liposomes. Although it appeared that the zeta potential is not a very sensitive parameter for tracking the hydrolysis reaction in phosphate buffer, generally zeta potential enables the characterization of such reactions through determination of electrokinetic properties of liposomes as well as the polydispersity and size distribution of the liposomes do.

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Section: Preparation Of Liposomesmentioning

confidence: 99%

Section: Preparation Of Liposomesmentioning

confidence: 99%

Zeta potential and surface charge of DPPC and DOPC liposomes in the presence of PLC enzyme

2016

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“…1,2 Local treatment of lung disorders via pulmonary drug delivery offers many advantages over oral or intravenous routes of administration, because direct deposition of drug at the diseased site could increase local drug concentrations, improve the pulmonary receptor occupancy, and reduce the overall dose required and the side effects that result from high doses of drug. 3 In addition, sustained-release formulations for pulmonary delivery may result in a favorable therapeutic index by prolonging drug action at the target site, reducing its side effects, and enhancing patient compliance.…”

Section: Introductionmentioning

confidence: 99%

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Sahib¹,

Darwis²,

Peh³

et al. 2011

IJN

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Background: Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization. Methods: PEG 5000 -DSPE polymeric micelles containing budesonide (BUD-SSMs) were prepared by the coprecipitation and reconstitution method, and the physicochemical and pharmacodynamic characteristics of BUD-SSMs were investigated. Results: The optimal concentration of solubilized budesonide at 5 mM PEG 5000 -DSPE was 605.71 ± 6.38 µg/mL, with a single-sized peak population determined by photon correlation spectroscopy and a particle size distribution of 21.51 ± 1.5 nm. The zeta potential of BUD-SSMs was −28.43 ± 1.98 mV. The percent entrapment efficiency, percent yield, and percent drug loading of the lyophilized formulations were 100.13% ± 1.09%, 97.98% ± 1.95%, and 2.01% ± 0.02%, respectively. Budesonide was found to be amorphous by differential scanning calorimetry, and had no chemical interaction with PEGylated polymer according to Fourier transform infrared spectroscopy. Transmission electron microscopic images of BUD-SSMs revealed spherical nanoparticles. BUD-SSMs exhibited prolonged dissolution behavior compared with Pulmicort Respules ® (P , 0.05). Aerodynamic characteristics indicated significantly higher deposition in the lungs compared with Pulmicort Respules ® . The mass median aerodynamic, geometric standard deviation, percent emitted dose, and the fine particle fraction were 2.83 ± 0.08 µm, 2.33 ± 0.04 µm, 59.13% ± 0.19%, and 52.31% ± 0.25%, respectively. Intratracheal administration of BUD-SSMs 23 hours before challenge (1 mg/kg) in an asthmatic/chronic obstructive pulmonary disease rat model led to a significant reduction in inflammatory cell counts (76.94 ± 5.11) in bronchoalveolar lavage fluid compared with administration of Pulmicort Respules ® (25.06 ± 6.91). Conclusion:The BUD-SSMs system might be advantageous for asthma or chronic obstructive pulmonary disease and other inflammatory airway diseases.

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“…A complex combination of molecular features such as high molecular weight (823 Da), amphotericity ( pK a1 in diluted water is 1.7, pK a2 in diluted water is 7.9 and the isoelectric point is 4.8) [13] and amphiphilicity challenges the development of pharmaceutical formulations [14] (scheme 1). Its intrinsic pH-dependent aqueous solubility ranges between 1 and 3 mg ml 21 [15].…”

Section: Introductionmentioning

confidence: 99%

Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

Morettón

Chiappetta

Sosnik

2011

J. R. Soc. Interface.

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Rifampicin-loadedpoly(e-caprolactone)-b-poly(ethylene glycol) -poly(e-caprolactone) flower-like polymeric micelles display low aqueous physical stability over time and undergo substantial secondary aggregation. To improve their physical stability, the lyoprotectionlyophilization process was thoroughly characterized. The preliminary cryoprotectant performance of mono-and disaccharides (e.g. maltose, glucose), hydroxypropyl-bcyclodextrin (HPbCD) and poly(ethylene glycol) (PEG) of different molecular weights was assessed in freeze -thawing assays at 2208C, 2808C and 21968C. The size and size distribution of the micelles at the different stages were measured by dynamic light scattering (DLS). A cryoprotectant factor ( f c ) was determined by taking the ratio between the size immediately after the addition of the cryoprotectant and the size after the preliminary freeze -thawing assay. The benefit of a synergistic cryoprotection by means of saccharide/ PEG mixtures was also assessed. Glucose (1 : 20), maltose (1 : 20), HPbCD (1 : 5) and glucose or maltose mixtures with PEG3350 (1 : 20) (copolymer:cryoprotectant weight ratio) were the most effective systems to protect 1 per cent micellar systems. Conversely, only HPbCD (1 : 5) cryoprotected more concentrated drug-loaded micelles (4% and 6%). Then, those micelle/ cryoprotectant systems that displayed f c values smaller than 2 were freeze-dried. The morphology of freeze-dried powders was characterized by scanning electron microscopy and atomic force microscopy and the residual water content analysed by the Karl Fisher method. The HPbCD-added lyophilisates were brittle porous cakes (residual water was between 0.8% and 3%), easily redispersable in water to form transparent systems with a minimal increase in the micellar size, as determined by DLS.

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Liposomes for drug delivery to the lungs by nebulization

Cited by 117 publications

References 31 publications

Zeta potential and surface charge of DPPC and DOPC liposomes in the presence of PLC enzyme

Zeta potential and surface charge of DPPC and DOPC liposomes in the presence of PLC enzyme

Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Cryoprotection–lyophilization and physical stabilization of rifampicin-loaded flower-like polymeric micelles

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