| 1. |
- Andersen, Anders J., et al.
(författare)
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Characterization of salmon calcitonin in spray-dried powder for inhalation : effect of formulation and process variables
- 2006
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Ingår i: 2006 AAPS Annual Meeting and Exposition. - : American Association of Pharmaceutical Scientists.
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Konferensbidrag (refereegranskat)abstract
- To characterize physicochemical properties of salmon calcitonin in spray-dried powder for inhalation and understand the interplay between stability, formulation and process parametersSalmon calcitonin (sCT) was spray-dried together with mannitol and chitosan that acts as stabiliser and absorption enhancer, respectively. Two process variables, i.e. inlet temperature and atomizing air volumetric flow rate, were investigated. Solid state properties of the spray-dried powders were characterized using SEM, TGA, XRPD and DSC. The physicochemical stability of salmon calcitonin in the dry powder was investigated by FTIR, HPLC and LC-MS techniques.A high yield of up to 80 % spray-dried powder was obtained with an improved cyclone assembled with B-290 Mini Spray Drier. Nevertheless, the yield was markedly reduced when addition of chitosan exceeded a certain proportion in spray drying formulation. XRPD and DSC results indicated that crystallinity of mannitol was inhibited with an increase of chitosan in the formulation. Residual moisture levels in the spray dried powders were 1-2%. As indicated by FTIR analysis, sCT retained its structural integrity under the spray drying conditions studied, i.e. 100-180 ºC inlet temperature and 357-742 L/h atomizing air volumetric flow rate. Addition of mannitol and chitosan in the spray drying formulation did not improve stabilization of sCT, in which around 7 % degraded impurities were found at a condition of 180 ºC inlet temperature. Yet no obvious degraded impurities were found in plain sCT spray-dried powder under the conditions studied. The LC-MS analysis showed that oxidation was the main degradation pathway at high inlet temperature. Other minor impurities originated from deamidation of Asn26, N-O acyl migration on Ser29 and dimerization by cross-linkage of the disulfide bonds. Two fragments, i.e. H-(Cys1-Gly28)-OH and H-(Ser29-Pro32)-NH2, could also be found when the degraded ester bond between Gly28 and Ser29 was further hydrolysed in phosphate buffer.Salmon calcitonin can be spray-dried into dry powders with good physical integrity under certain conditions. Chemical stability of sCT in spray-dried powder could be improved by the optimization of formulation and process variables.
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| 2. |
- Wan, Feng, et al.
(författare)
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Lipid Shell-Enveloped Polymeric Nanoparticles with High Integrity of Lipid Shells Improve Mucus Penetration and Interaction with Cystic Fibrosis-Related Bacterial Biofilms
- 2018
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 10:13, s. 10678-10687
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticle (NP) mediated drug delivery into viscous biomatrices, e.g., mucus and bacterial biofilms, is challenging. Lipid shell-enveloped polymeric NPs (Lipid@NPs), composed of a polymeric NP core coated with a lipid shell, represent a promising alternative to the current delivery systems. Here, we describe the facile methods to prepare Lipid@NPs with high integrity of lipid shells and demonstrate the potential of Lipid@NPs in an effective mucus penetration and interaction with cystic fibrosis-related bacterial biofilms. Lipid shell-enveloped polystyrene NPs with high integrity of lipid shells (cLipid@PSNPs) were prepared by using an electrostatically mediated layer-by-layer approach, where the model polystyrene NPs (PSNPs) were first modified with positively charged poly-l-lysine (PLL) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), followed by subsequent fusion with zwitterionic, PEGylated small unilamellar vesicles (SUVs). The interaction of the PSNPs with SUVs was significantly enhanced by modifying the PSNPs with PLL and DOTAP, which eventually resulted in the formation of cLipid@PSNPs, i.e., Lipid@PLL-PSNPs and Lipid@DOTAP-PSNPs. Improved mucus-penetrating property of cLipid@PSNPs was demonstrated by quartz crystal microbalance with dissipation monitoring measurements. Furthermore, fluorescence resonance energy transfer measurements showed that the interaction of the cLipid@PSNPs with bacterial biofilms was significantly promoted. In conclusion, we prepared cLipid@PSNPs via an electrostatically mediated layer-by-layer approach. Our results suggest that the integrity of the lipid envelopes is crucial for enabling the diffusion of Lipid@PSNPs into the mucus layer and promoting the interaction of Lipid@PSNPs with a bacterial biofilm.
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| 3. |
- Wan, Feng, et al.
(författare)
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Qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant by using quartz crystal microbalance with dissipation monitoring
- 2019
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797. ; 545, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the interaction between inhaled nanoparticles and pulmonary surfactant is a prerequisite for predicting the fate of inhaled nanoparticles. Here, we introduce a quartz crystal microbalance with dissipation monitoring (QCM-D)-based methodology to reveal the extent and nature of the biophysical interactions of polymer- and lipid-based nanoparticles with pulmonary surfactant. By fitting the QCM-D data to the Langmuir adsorption equation, we determined the kinetics and equilibrium parameters [i.e., maximal adsorption (Δm max ), equilibrium constant (K a ), adsorption rate constant (k a ) and desorption rate constant (k d )] of polymeric nanoparticles adsorption onto the pulmonary surfactant (e.g., an artificial lipid mixture and an extract of porcine lung surfactant). Furthermore, our results revealed that the nature of the interactions between lipid-based nanoparticles (e.g., liposomes) and pulmonary surfactant was governed by the liposomal composition, i.e., incorporation of cholesterol and PEGylated phospholipid (DSPE-PEG 2000 ) into DOPC-based liposomes led to the adsorption of intact liposomes onto the pulmonary surfactant layer and the mass exchange between the liposomes and pulmonary surfactant layer, respectively. In conclusion, we demonstrate the applicability of the QCM-D technique for qualitative and quantitative analysis of the biophysical interaction of inhaled nanoparticles with pulmonary surfactant, which is vital for rational design and optimization of inhalable nanomedicines.
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| 4. |
- Yang, Mingshi, et al.
(författare)
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Characterisation of salmon calcitonin in spray-dried powder for inhalation : effect of chitosan
- 2007
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 331:2, s. 176-81
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Tidskriftsartikel (refereegranskat)abstract
- Salmon calcitonin (sCT) powders suitable for inhalation, containing chitosan and mannitol as absorption enhancer and protection agent, respectively, were prepared using a spray-drying process. The effect of chitosan on physicochemical stability of sCT in the dry powder was investigated by different analytical techniques. High-performance liquid chromatography (HPLC) analysis indicated that sCT was chemically stable upon spray-drying. With the proportion of chitosan in spray-drying formulation being increased, dissolution of sCT from the dry powders was decreased both in phosphate buffer and acetate buffer. The thioflavine T fluorescence assay showed that no fibrils were present in the spray-dried powder. However, sCT partly fibrillated in the phosphate buffer, but not in acetate buffer. Fourier transform infrared (FTIR) spectra showed that the secondary structure of sCT was slightly changed in the dry powder, yet no aggregate signal was observed. Circular dichroism analysis indicated that the structure of sCT in an aqueous formulation was slightly altered by addition of chitosan. Nevertheless, recovery of sCT was not influenced by chitosan in the aqueous formulation as indicated by HPLC analysis. This study suggested that sCT, in absence of any additives, was stable during the spray-drying process under certain conditions. Addition of chitosan affects recovery of sCT from spray-dried powders, which may be due to formation of a partially irreversible complex between the protein and chitosan during the spray-drying process.
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