| 1. |
- Bodvik, Rasmus, et al.
(författare)
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Aggregation and network formation of aqueous methylcellulose and hydroxypropylmethylcellulose solutions.
- 2010
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Ingår i: Colloids and Surfaces A. - : Elsevier. - 0927-7757 .- 1873-4359. ; 354:1-3, s. 162-171
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Tidskriftsartikel (refereegranskat)abstract
- Solution properties of methylcellulose (MC) and hydroxypropylmethylcellulose (HPMC) have been investigated as a function of temperature and concentration using a broad range of experimental techniques. Novelties include the extensive comparison between MC and HPMC solutions as well as the combination of techniques, and the use of Cryo transmission electron microscopy (Cryo-TEM). The correlation between rheology and light scattering results clearly demonstrates the relation between viscosity change and aggregation. Cryo-TEM images show the network structures formed. Viscosity measurements show that for both MC and HPMC solutions sudden changes in viscosity occur as the temperature is increased. The onset temperature for these changes depends on polymer concentration and heating rate. For both MC and HPMC solutions the viscosity on cooling is very different compared to on heating, demonstrating the slow equilibration time. The viscosity changes in MC and HPMC solutions are dramatically different; for MC solutions the viscosity increases by several orders of magnitude when a critical temperature is reached, whereas for HPMC solutions the viscosity decreases abruptly at a given temperature, followed by an increase upon further heating. Light and (SAXS) small-angle X-ray scattering shows that the increase in viscosity, for MC as well as for HPMC solutions, is due to extensive aggregation of the polymers. Light scattering also provides information on aggregation kinetics. The SAXS measurements allow us to correlate aggregation hysteresis to the viscosity hysteresis, as well as to extract some structural information. Cryo-TEM images give novel information that a fibrillar network is formed in MC solutions, and the strong viscosity increase occurs when this network spans the whole solution volume. For HPMC solutions the behaviour is more complex. The decrease in viscosity can be related to the formation of compact objects, and the subsequent increase to formation of fibrillar structures, which are more linear and less entangled than for MC.
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| 2. |
- Bodvik, Rasmus, et al.
(författare)
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Aggregation of modified celluloses in aqueous solution : transition from methylcellulose to hydroxypropylmethylcellulose solution properties induced by a low molecular weight oxyethylene additive
- 2012
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 28:38, s. 13562-13569
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Tidskriftsartikel (refereegranskat)abstract
- Temperature effects on viscosity and aggregation behaviour of aqueous solutions of three different cellulose ethers: methylcellulose (MC), hydroxypropylmethylcellulose (HPMC) and ethyl(hydroxyethyl)cellulose (EHEC), were investigated using viscosity and dynamic light scattering measurements as well as Cryo-TEM. In all cases increasing temperature reduces the solvent quality of water, which induces aggregation. It was found that the aggregation rate followed the order EHEC > HPMC > MC, suggesting that cellulose ethers containing some bulky and partly hydrophilic substituents assemble into large aggregates more readly than methylcellulose. This finding is discussed in terms of the organization of the structures formed by the different cellulose ethers. The temperature-dependent association behavior of cellulose ethers was also investigated in a novel way by adding diethyleneglycolmonobutylether (BDG) to methylcellulose aqueous solutions. When the concentration of BDG was at and above 5 wt%, methylcellulose adopted HPMC-like solution behaviour. In particular, a transition temperature where the viscosity was decreasing, prior to increasing at higher temperatures, appeared and the aggregation rate increased. This observation is rationalized by the ability of the amphiphilic BDG to accumulate at non-polar interfaces, and thus also to associate with hydrophobic regions of methylcellulose. In effect BDG is suggested to act as a physisorbed hydrophilic and bulky substituent inducing similar constraints on aggregation as the chemically attached hydroxypropyl groups in HPMC and oligo(ethyleneoxide) chains in EHEC.
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| 3. |
- Boge, Lukas, 1987, et al.
(författare)
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Cubosomes post-loaded with antimicrobial peptides: Characterization, bactericidal effect and proteolytic stability
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 526:1-2, s. 400-412
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Tidskriftsartikel (refereegranskat)abstract
- Novel antibiotics, such as antimicrobial peptides (AMPs), have recently attended more and more attraction. In this work, dispersed cubic liquid crystalline gel (cubosomes) was used as drug delivery vehicles for three AMPs (AP114, DPK-060 and LL-37). Association of peptides onto cubosomes was studied at two cubosome/peptide ratios using high performance liquid chromatography, ?-potential and circular dichroism measurements. AMPs impact on the cubosome structure was investigated using small angle x-ray scattering and cryogenic transmission electron microscopy. The antimicrobial effect of the AMP loaded cubosomes was studied in vitro by minimum inhibitory concentration and time-kill assays. Proteolytic protection was investigated by incubating the formulations with two elastases and the antimicrobial effect after proteolysis was studied using radial diffusion assay. Different association efficacy onto the cubosomes was observed among the AMPs, with LL-37 showing greatest association (>60%). AP114 loaded cubosomes displayed a preserved antimicrobial effect, whereas for LL-37 the broad spectrum bacterial killing was reduced to only comprise Gram-negative bacteria. Interestingly, DPK-060 loaded cubosomes showed a slight enhanced effect against S. aureus and E. coli strains. Moreover, the cubosomes were found to protect LL-37 from proteolytic degradation, resulting in a significantly better bactericidal effect after being subjected to elastase, compared to unformulated peptide.
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| 4. |
- Boge, Lukas, et al.
(författare)
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Freeze-dried and re-hydrated liquid crystalline nanoparticles stabilized with disaccharides for drug-delivery of the plectasin derivative AP114 antimicrobial peptide
- 2018
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 0021-9797 .- 1095-7103. ; 522, s. 126-135
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Tidskriftsartikel (refereegranskat)abstract
- Liquid crystalline nanoparticles (LCNPs), e.g. cubosomes and hexosomes, are receiving more and more attraction as drug delivery vehicles. Dry powder formulation that forms LCNPs upon hydration can be advantageous to make new routes of administration accessible. In this work, we investigate use of three disaccharides (lactose, trehalose and sucrose) as protective matrices for glycerol monooleate based LCNP forming powders produced by freeze-drying. Phase behavior, particle size and size distributions at the different preparation steps were monitored by small angle x-ray scattering (SAXS) and dynamic light scattering (DLS). Particle appearance was imaged by cryogenic transmission electron microscopy (cryo-TEM). Moreover, the therapeutic relevant antimicrobial peptide AP114 (plectasin derivative) was incorporated in the formulations. Peptide encapsulation and release as well as in vitro antibacterial effect were investigated. Results showed that all freeze-dried powders did form particles with liquid crystalline structure upon hydration. However, a phase transition from the bicontinuous cubic Pn3m to the reversed hexagonal was observed, as a consequence of sugar addition and the freeze-drying procedure. Data indicates that trehalose is the preferred choice of lyo-protectant in order to maintain a mono-modal particle size distribution. In addition, antimicrobial activity of AP114-containing formulations was found to be highest for the formulation containing trehalose. The release kinetics of AP114 from the nanoparticles was strongly affected by the dimensions of the hexagonal phase. Larger dimension of the hexagonal phase, significantly improved the release of AP114 and antimicrobial activity of the formulation.
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| 5. |
- Boge, Lukas, et al.
(författare)
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Lipid-based liquid crystals as carriers for antimicrobial peptides : Phase behavior and antimicrobial effect
- 2016
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:17, s. 4217-4228
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Tidskriftsartikel (refereegranskat)abstract
- The number of antibiotic-resistant bacteria is increasing worldwide, and the demand for novel antimicrobials is constantly growing. Antimicrobial peptides (AMPs) could be an important part of future treatment strategies of various bacterial infection diseases. However, AMPs have relatively low stability, because of proteolytic and chemical degradation. As a consequence, carrier systems protecting the AMPs are greatly needed, to achieve efficient treatments. In addition, the carrier system also must administrate the peptide in a controlled manner to match the therapeutic dose window. In this work, lyotropic liquid crystalline (LC) structures consisting of cubic glycerol monooleate/water and hexagonal glycerol monooleate/oleic acid/water have been examined as carriers for AMPs. These LC structures have the capability of solubilizing both hydrophilic and hydrophobic substances, as well as being biocompatible and biodegradable. Both bulk gels and discrete dispersed structures (i.e., cubosomes and hexosomes) have been studied. Three AMPs have been investigated with respect to phase stability of the LC structures and antimicrobial effect: AP114, DPK-060, and LL-37. Characterization of the LC structures was performed using small-angle X-ray scattering (SAXS), dynamic light scattering, ζ-potential, and cryogenic transmission electron microscopy (Cryo-TEM) and peptide loading efficacy by ultra performance liquid chromatography. The antimicrobial effect of the LCNPs was investigated in vitro using minimum inhibitory concentration (MIC) and time-kill assay. The most hydrophobic peptide (AP114) was shown to induce an increase in negative curvature of the cubic LC system. The most polar peptide (DPK-060) induced a decrease in negative curvature while LL-37 did not change the LC phase at all. The hexagonal LC phase was not affected by any of the AMPs. Moreover, cubosomes loaded with peptides AP114 and DPK-060 showed preserved antimicrobial activity, whereas particles loaded with peptide LL-37 displayed a loss in its broad-spectrum bactericidal properties. AMP-loaded hexosomes showed a reduction in antimicrobial activity.
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| 6. |
- Urimi, Dileep, et al.
(författare)
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Formulation development and upscaling of lipid nanocapsules as a drug delivery system for a novel cyclic GMP analogue intended for retinal drug delivery
- 2021
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 602
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Tidskriftsartikel (refereegranskat)abstract
- Lipid nanocapsules (LNCs) were prepared with a novel cyclic GMP analogue, DF003, intended for the treatment of neurodegenerative retinal degenerations. LNCs loaded with DF003 were prepared by a phase inversion method and characterized for particle size, polydispersity index, drug loading, entrapment efficiency, stability, and in vitro drug release. Particle size, PdI and zeta potential of selected optimized formulation were 76 ± 1.2 nm, 0.16 ± 0.02, and −11.6 ± 0.4 mV, respectively, with an entrapment efficiency of 69 ± 0.5%. The selected formulation showed a sustained drug release for up to 6 days in phosphate buffer as well as in vitreous components. Stability evaluation of LNCs in presence of vitreous components demonstrated structural stability and compatibility. Further, the nanoparticle preparation process was upscaled to 1000 times (10 L) of the typical lab scale (0.01 L). Product parameters were observed to be unaffected by the upscaling, demonstrating that the LNCs were of the same quality as those prepared at lab scale. Additionally, the manufacturing process was adapted and assessed for a continuous production of LNCs to leverage it for industrial viability. Overall, these findings reveal the remarkable potential of LNCs as drug delivery vehicles and their possibility for clinical translation.
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| 7. |
- Urimi, Dileep, et al.
(författare)
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Structural Characterization Study of a Lipid Nanocapsule Formulation Intended for Drug Delivery Applications Using Small-Angle Scattering Techniques
- 2022
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 19:4, s. 1068-1077
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Tidskriftsartikel (refereegranskat)abstract
- Lipid nanocapsules (LNCs) are increasingly being used for various drug delivery applications due to their versatile nature and ability to carry a wide variety of therapeutic drug molecules. In the present investigation, small-angle X-ray (SAXS) and neutron scattering (SANS) techniques were used to elucidate the structure of LNCs. Overall, size measurements obtained from SAXS and SANS techniques were complemented with dynamic light scattering, zeta potential, and cryogenic transmission electron microscopy measurements. The structural aspects of LNCs can be affected by drug loading and the properties of the drug. Here, the impact of drug loading on the overall structure was evaluated using DF003 as a model drug molecule. LNCs with varying compositions were prepared using a phase inversion method. Combined analysis of SAXS and SANS measurements indicated the presence of a core-shell structure in the LNCs. Further, the drug loading did not alter the overall core-shell structure of the LNCs. SANS data revealed that the core size remained unchanged with a radius of 20.0 +/- 0.9 nm for unloaded LNCs and 20.2 +/- 0.6 nm for drug-loaded LNCs. Furthermore, interestingly, the shell becomes thicker in an order of similar to 1 nm in presence of the drug compared to the shell thickness of unloaded LNCs as demonstrated by SAXS data. This can be correlated with the strong association of hydrophilic DF003 with Kolliphor HS 15, a polyethylene glycol-based surfactant that predominantly makes up the shell, resulting in a drug-rich hydrated shell.
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