| 1. |
- Badell, Maria Valldeperas, et al.
(författare)
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Lipid Sponge-Phase Nanoparticles as Carriers for Enzymes
- 2018
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Ingår i: Biophysical Journal. - : Cell Press. - 0006-3495 .- 1542-0086. ; 114:3, suppl 1, s. 15A-15A
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Immobilization of enzymes into different support materials has been widely studied as means to control their activity and stability. Here we will consider lipid liquid crystalline phases as enzyme carriers, as they have been demonstrated to have a high potential in a range of applications such as drug delivery, protein encapsulation or crystallization thanks to the wide range of self-assembly structures they can form, which have cavities of nano-scale dimensions. Furthermore, such structures have also been observed in a range of living organisms. Although, reverse cubic or hexagonal lipid aqueous phase can be used to entrap smaller biomolecules, it is still challenging to encapsulate bioactive macromolecules, such as proteins. Here, we will present a novel lipid system able to form highly swollen sponge phases (L3), with aqueous pores up to 13 nm of diameter. We will show that this structure is preserved even in excess aqueous solution, where they form sponge-like nanoparticles (L3 NPs) in which two enzymes of different sizes, Aspartic protease and beta-galactosidase (34 KDa and 460 KDa, respectively), could be included. To reveal the nature of the interaction between the enzymes and the lipid matrix, we studied the adsorption of both proteins on the lipid layers formed by the L3 NPs. The results will be discussed in terms of the ability of these nanoparticles to encapsulate and release of the proteins in the lipid matrix.
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| 2. |
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| 3. |
- Burrell, Jamie, et al.
(författare)
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Using Curvature Power to Map the Domain of Inverse Micellar Cubic Phases : The Case of Aliphatic Aldehydes in 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine
- 2017
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 33:44, s. 12804-12813
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Tidskriftsartikel (refereegranskat)abstract
- Oxylipins, or fatty aldehydes, are a class of molecules produced from membrane lipids as a result of oxidative stress or enzyme-mediated peroxidation. Here we report the effects of two biologically important fatty aldehydes, trans,trans-2,4-decanedienal (DD) and cis-11-hexadecenal (HD), on the phase behavior of the lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) in water. We compare the phase behavior of DD/DOPE and HD/DOPE mixtures to the phase behavior of oleic acid/DOPE mixtures and show that DD, HD, and oleic acid have similar effects on the phase diagrams of DOPE. Notably, both DD and HD, like oleic acid, induce the formation of Fd3m inverse micellar cubic phases in DOPE/water mixtures. This is the first time that Fd3m phases in fatty aldehyde-containing mixtures have been reported. We assess the effects of DD, HD, and oleic acid on DOPE in terms of lipid spontaneous curvatures and propose a method to predict the formation of Fd3m phases from the curvature power of amphiphiles. This methodology predicts that Fd3m phases will become stable if the spontaneous curvature of a lipid mixture is -0.48 ± 0.05 nm-1 or less.
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| 4. |
- Dabkowska, Aleksandra P., et al.
(författare)
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Non-lamellar lipid assembly at interfaces : controlling layer structure by responsive nanogel particles
- 2017
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Ingår i: Interface Focus. - : ROYAL SOC. - 2042-8898 .- 2042-8901. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Biological membranes do not only occur as planar bilayer structures, but depending on the lipid composition, can also curve into intriguing three-dimensional structures. In order to fully understand the biological implications as well as to reveal the full potential for applications, e.g. for drug delivery and other biomedical devices, of such structures, well-defined model systems are required. Here, we discuss the formation of lipid non-lamellar liquid crystalline (LC) surface layers spin-coated from the constituting lipids followed by hydration of the lipid layer. We demonstrate that hybrid lipid polymer films can be formed with different properties compared with the neat lipid LC layers. The nanostructure and morphologies of the lipid films formed reflect those in the bulk. Most notably, mixed lipid layers, which are composed of glycerol monooleate and diglycerol monooleate with poly(N-isopropylacrylamide) nanogels, can form films of reverse cubic phases that are capable of responding to temperature stimulus. Owing to the presence of the nanogel particles, changing the temperature not only regulates the hydration of the cubic phase lipid films, but also the lateral organization of the lipid domains within the lipid self-assembled film. This opens up the possibility for new nanostructured materials based on lipid-polymer responsive layers.
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| 5. |
- Dymond, Marcus K., et al.
(författare)
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Lipid Spontaneous Curvatures Estimated from Temperature-Dependent Changes in Inverse Hexagonal Phase Lattice Parameters : Effects of Metal Cations
- 2016
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 32:39, s. 10083-10092
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Tidskriftsartikel (refereegranskat)abstract
- Recently we reported a method for estimating the spontaneous curvatures of lipids from temperature-dependent changes in the lattice parameter of inverse hexagonal liquid crystal phases of binary lipid mixtures. This method makes use of 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE) as a host lipid, which preferentially forms an inverse hexagonal phase to which a guest lipid of unknown spontaneous curvature is added. The lattice parameters of these binary lipid mixtures are determined by small-angle X-ray diffraction at a range of temperatures and the spontaneous curvature of the guest lipid is determined from these data. Here we report the use of this method on a wide range of lipids under different ionic conditions. We demonstrate that our method provides spontaneous curvature values for DOPE, cholesterol, and monoolein that are within the range of values reported in the literature. Anionic lipids 1,2-dioleoyl-sn-glycerol-3-phosphatidic acid (DOPA) and 1,2-dioleoyl-sn-glycerol-3-phosphoserine (DOPS) were found to exhibit spontaneous curvatures that depend on the concentration of divalent cations present in the mixtures. We show that the range of curvatures estimated experimentally for DOPA and DOPS can be explained by a series of equilibria arising from lipid-cation exchange reactions. Our data indicate a universal relationship between the spontaneous curvature of a lipid and the extent to which it affects the lattice parameter of the hexagonal phase of DOPE when it is part of a binary mixture. This universal relationship affords a rapid way of estimating the spontaneous curvatures of lipids that are expensive, only available in small amounts, or are of limited chemical stability.
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| 6. |
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| 7. |
- Gilbert, Jennifer, et al.
(författare)
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Immobilisation of β-galactosidase within a lipid sponge phase: structure, stability and kinetics characterisation
- 2019
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Ingår i: Nanoscale. - 2040-3372. ; 11:44, s. 21291-21301
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Tidskriftsartikel (refereegranskat)abstract
- In the formulation of an active enzyme enclosed in a matrix for controlled delivery, it is a challenge to achieve a high protein load and to ensure high activity of the protein. For the first time to our knowledge, we report the use of a highly swollen lipid sponge (L3) phase for encapsulation of the large active enzyme, β-galactosidase (β-gal, 238 kDa). This enzyme has large relevance for applications in, e.g. the production of lactose free milk products. The formulation consisted of diglycerol monooleate (DGMO), and a mixture of mono-, di- and triglycerides (Capmul GMO-50) stabilised by polysorbate 80 (P80). The advantage of this type of matrix is that it can be produced on a large scale with a fairly simple and mild process as the system is in practice self-dispersing, yet it has a well-defined internal nano-structure. Minor effects on the sponge phase structure due to the inclusion of the enzyme were observed using small angle X-ray scattering (SAXS). The effect of encapsulation on the enzymatic activity and kinetic characteristics of β-galactosidase activity was also investigated and can be related to the enzyme stability and confinement within the lipid matrix. The encapsulated β-galactosidase maintained its activity for a significantly longer time when compared to the free solution at the same temperature. Differences in the particle size and charge of sponge-like nanoparticles (L3-NPs) with and without the enzyme were analysed by dynamic light scattering (DLS) and zeta-potential measurements. Moreover, all the initial β-galactosidase was encapsulated within L3-NPs as revealed by size exclusion chromatography.
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| 8. |
- Luchini, Alessandra, et al.
(författare)
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Neutron Reflectometry reveals the interaction between functionalized SPIONs and the surface of lipid bilayers
- 2017
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Ingår i: Colloids and Surfaces B. - : ELSEVIER SCIENCE BV. - 0927-7765 .- 1873-4367. ; 151, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- The safe application of nanotechnology devices in biomedicine requires fundamental understanding on how they interact with and affect the different components of biological systems. In this respect, the cellular membrane, the cell envelope, certainly represents an important target or barrier for nanosystems. Here we report on the interaction between functionalized SuperParamagnetic Iron Oxide Nanoparticles (SPIONs), promising contrast agents for Magnetic Resonance Imaging (MRI), and lipid bilayers that mimic the plasma membrane. Neutron Reflectometry, supported by Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) experiments, was used to characterize this interaction by varying both SPION coating and lipid bilayer composition. In particular, the interaction of two different SPIONs, functionalized with a cationic surfactant and a zwitterionic phospholipid, and lipid bilayers, containing different amount of cholesterol, were compared. The obtained results were further validated by Dynamic Light Scattering (DLS) measurements and Cryogenic Transmission Electron Microscopy (Cryo-TEM) images. None of the investigated functionalized SPIONs were found to disrupt the lipid membrane. However, in all case we observed the attachment of the functionalized SPIONs onto the surface of the bilayers, which was affected by the bilayer rigidity, i.e. the cholesterol concentration.
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| 9. |
- Nylander, Charlotte, 1979-, et al.
(författare)
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Previously undiagnosed attention-deficit/hyperactivity disorder associated with poor metabolic control in adolescents with type 1 diabetes
- 2018
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 19:4, s. 816-822
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Tidskriftsartikel (refereegranskat)abstract
- Background: Managing modern diabetes treatment requires efficient executive functions. Patients with attention-deficit/hyperactivity disorder (ADHD) and type 1 diabetes have poor metabolic control and present with ketoacidosis more often than patients without ADHD. Objective: To assess whether patients with type 1 diabetes and with indications of executive problems met criteria for ADHD, and to investigate whether these patients had difficulties achieving metabolic control. Methods: In a hospital-based study, including 3 pediatric departments at hospitals in Stockholm and Uppsala, Sweden, questionnaires regarding executive problems had been filled out by 12- to 18-year-old patients with type 1 diabetes and their parents. Out of 166 patients with completed questionnaires, 49 were selected for a clinical study due to reported executive problems/ADHD symptoms. However, 7 already had a diagnosis of ADHD, 21 denied follow-up, 8 did not respond, leaving 13 adolescents for the clinical assessment. Results: Of the clinically assessed adolescents, 9 (6 girls) met criteria for ADHD. Patients who did not respond to the follow-up and patients who were diagnosed with ADHD within the study, showed to a larger extent than the other study groups high HbA1c levels (>70 mmol/mol, 8,6%). HbA1c >70 mmol/mol (8.6%) was associated with diagnosed ADHD (prior to or within the study), odds ratio 2.96 (95% confidence interval 1.02-8.60). Conclusion: Patients with type 1 diabetes and poor metabolic control should be assessed with regard to ADHD. There is a need for paying special attention to girls with poor metabolic control.
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| 10. |
- Nylander, Ruta
(författare)
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Magnetic resonance imaging markers of cerebral small vessel disease in an elderly population – association with cardiovascular disease and cognitive function
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cerebral small vessel disease (SVD) is identifiable by clinical, neuroimaging, neuropathological and cognitive findings.The aim of this thesis was to assess SVD and cerebral perfusion on magnetic resonance imaging (MRI) in a 75-year-old population and compare the findings with scars of myocardial infarctions, cardiovascular risk markers and cognitive function. In addition, the evolution of SVD over 5 years was studied.The study population included subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The subjects had been chosen in a randomized manner from the register of the municipality. MRI of the brain and the heart, cognitive tests and blood tests for cardiovascular risk factors were performed in 406 subjects at age 75 years and 250 of them were re-examined 5 years later at the age of 80.Paper 1 showed that unrecognized myocardial infarctions (UMIs) were found in 120 subjects (30%) and recognized myocardial infarctions (RMIs) in 21 (5%). Men with RMIs displayed an increased prevalence of cortical and lacunar cerebral infarctions, whereas women with UMIs more frequently had cortical cerebral infarctions.Paper 2 showed that one or more brain infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts and 2% had both). Hypertension and obesity were significantly associated with an increased risk of infarction. The newer risk markers investigated were not significantly associated with brain infarcts.Paper 3 showed that MRI manifestations of SVD progressed over 5 years. Relative cerebral blood flow (rCBF) was not associated with WMH volume or progression of WMH volume.Paper 4 showed that moderate to severe WMHs and incident lacunar infarcts on brain MRI were associated with a mild impairment of executive function.In conclusion, this longitudinal population based study compares MRI manifestations of SVD with clinical data, providing knowledge that may be used in further investigations of preventive interventions and for identification of disease in early stages.
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| 11. |
- Pehrsson, S., et al.
(författare)
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Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin
- 2017
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7836 .- 1538-7933. ; 15:6, s. 1213-1222
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Tidskriftsartikel (refereegranskat)abstract
- Background: Ticagrelor, a P2Y12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective: To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods: Pigs, pretreated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results: MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: bodyweight- adjusted blood loss in the 15-to 90-min interval, 12 (confidence interval [ CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg(-1) (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.1350.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.030.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94136) mmHg (aspirin alone). Conclusion: MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADPinduced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival.
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| 12. |
- Prost, Stefan, et al.
(författare)
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Comparative analyses identify genomic features potentially involved in the evolution of birds-of-paradise
- 2019
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Ingår i: GigaScience. - : OXFORD UNIV PRESS. - 2047-217X. ; 8:5
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Tidskriftsartikel (refereegranskat)abstract
- The diverse array of phenotypes and courtship displays exhibited by birds-of-paradise have long fascinated scientists and nonscientists alike. Remarkably, almost nothing is known about the genomics of this iconic radiation. There are 41 species in 16 genera currently recognized within the birds-of-paradise family (Paradisaeidae), most of which are endemic to the island of New Guinea. In this study, we sequenced genomes of representatives from all five major clades within this family to characterize genomic changes that may have played a role in the evolution of the group's extensive phenotypic diversity. We found genes important for coloration, morphology, and feather and eye development to be under positive selection. In birds-of-paradise with complex lekking systems and strong sexual dimorphism, the core birds-of-paradise, we found Gene Ontology categories for "startle response" and "olfactory receptor activity" to be enriched among the gene families expanding significantly faster compared to the other birds in our study. Furthermore, we found novel families of retrovirus-like retrotransposons active in all three de novo genomes since the early diversification of the birds-of-paradise group, which might have played a role in the evolution of this fascinating group of birds.
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| 13. |
- Sgaramella, Nicola, et al.
(författare)
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Expression of p16 in squamous cell carcinoma of the mobile tongue is independent of HPV infection despite presence of the HPV-receptor syndecan-1
- 2015
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 113:2, s. 321-326
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tongue squamous cell carcinoma (TSCC) is increasing in incidence, especially among young patients and preferably females. Infection with human papilloma virus (HPV) has been suggested as a cause of SCC in the head and neck, and the proportion of oropharyngeal cancers caused by HPV has steadily increased. Methods: Samples from 109 patients with primary TSCC were analysed for the presence of HPV16 by in situ hybridisation and for expression of its surrogate marker p16 and the HPV receptor syndecan-1 by immunhistochemistry. Results: No evidence of HPV16 DNA was observed in the tumours, although one-third showed p16 staining. There was no difference in the expression of the primary HPV receptor, syndecan-1, between TSCC and a group of tonsil SCC. Conclusion: Whereas p16 is expressed in some TSCCs, HPV16 is undetectable, therefore, p16 cannot be used as a surrogate marker for high-risk HPV-infection in this tumour. Despite presence of the HPV-receptor syndecan-1 in TSCC, HPV prefers the tonsillar environment. Lack of p16 associates with worse prognosis primarily in patients aged <= 40 years with tongue SCC. The improved prognosis seen in p16-positive TSCC can be due to induction of a senescent phenotype or an inherent radiosensitivity due to the ability of p16 to inhibit homologous recombination repair.
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| 14. |
- Tournillon, A-S, et al.
(författare)
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p53 binds the mdmx mRNA and controls its translation
- 2017
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Ingår i: Oncogene. - : NATURE PUBLISHING GROUP. - 0950-9232 .- 1476-5594. ; 36:5, s. 723-730
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Tidskriftsartikel (refereegranskat)abstract
- MDMX and MDM2 are two nonredundant essential regulators of p53 tumor suppressor activity. MDM2 controls p53 expression levels, whereas MDMX is predominantly a negative regulator of p53 trans-activity. The feedback loops between MDM2 and p53 are well studied and involve both negative and positive regulation on transcriptional, translational and post-translational levels but little is known on the regulatory pathways between p53 and MDMX. Here we show that overexpression of p53 suppresses mdmx mRNA translation in vitro and in cell-based assays. The core domain of p53 binds the 5' untranslated region (UTR) of the mdmx mRNA in a zinc-dependent manner that together with a trans-suppression domain located in p53 N-terminus controls MDMX synthesis. This interaction can be visualized in the nuclear and cytoplasmic compartment. Fusion of the mdmx 5' UTR to the ovalbumin open reading frame leads to suppression of ovalbumin synthesis. Interestingly, the transcription inactive p53 mutant R273H has a different RNA-binding profile compared with the wild-type p53 and differentiates the synthesis of MDMX isoforms. This study describes p53 as a trans-suppressor of the mdmx mRNA and adds a further level to the intricate feedback system that exist between p53 and its key regulatory factors and emphasizes the important role of mRNA translation control in regulating protein expression in the p53 pathway.
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| 15. |
- Valldeperas, Maria, et al.
(författare)
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Encapsulation of Aspartic Protease in Nonlamellar Lipid Liquid Crystalline Phases
- 2019
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495. ; 117:5, s. 829-843
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Tidskriftsartikel (refereegranskat)abstract
- Encapsulation of proteins within lipid inverse bicontinuous cubic phases (Q2) has been widely studied for many applications, such as protein crystallization or drug delivery of proteins for food and pharmaceutical purposes. However, the use of the lipid sponge (L3) phase for encapsulation of proteins has not yet been well explored. Here, we have employed a lipid system that forms highly swollen sponge phases to entrap aspartic protease (34 kDa), an enzyme used for food processing, e.g., to control the cheese-ripening process. Small-angle x-ray scattering showed that although the L3 phase was maintained at low enzyme concentrations (≤15 mg/mL), higher concentration induces a transition to more curved structures, i.e., transition from L3 to inverse bicontinuous cubic (Q2) phase. The Raman spectroscopy data showed minor conformational changes assigned to the lipid molecules that confirm the lipid-protein interactions. However, the peaks assigned to the protein showed that the structure was not significantly affected. This was consistent with the higher activity presented by the encapsulated aspartic protease compared to the free enzyme stored at the same temperature. Finally, the encapsulation efficiency of aspartic protease in lipid sponge-like nanoparticles was 81% as examined by size-exclusion chromatography. Based on these results, we discuss the large potential of lipid sponge phases as carriers for proteins.
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| 16. |
- Valldeperas, Maria, et al.
(författare)
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Interfacial properties of lipid sponge-like nanoparticles and the role of stabilizer on particle structure and surface interactions
- 2019
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Ingår i: Soft Matter. - : ROYAL SOC CHEMISTRY. - 1744-683X .- 1744-6848. ; 15:10, s. 2178-2189
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Tidskriftsartikel (refereegranskat)abstract
- The advantage of using nonlamellar lipid liquid crystalline phases has been demonstrated in many applications, such as drug delivery, protein encapsulation and crystallisation. We have recently reported that a mixture of mono-and diglycerides is able to form sponge-like nanoparticles (L-3-NPs) with large enough aqueous pores to encapsulate macromolecules such as proteins. Here we use small angle neutron scattering (SANS) to reveal morphology, structural and chemical composition of these polysorbate 80 (P80) stabilized sponge phase nanoparticles, not previously known. Our results suggest that L-3-NPs have a core-shell sphere structure, with a shell rich in P80. It was also found that even if P80 is mostly located on the surface, it also contributes to the formation of the inner sponge phase structure. An important aspect for the application and colloidal stability of these particles is their interfacial properties. Therefore, the interfacial behaviour of the nanoparticles on hydrophilic silica was revealed by Quartz crystal microbalance with dissipation (QCM-D) and neutron reflectivity (NR). Adsorption experiments reveal the formation of a thin lipid layer, with the dimension corresponding to a lipid bilayer after L-3-NPs are in contact with hydrophilic silica. This suggests that the diglycerol monoleate/ Capmul GMO-50/P80 particles reorganize themselves on this surface, probably due to interactions between P80 head group and SiO2.
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| 17. |
- Wadsäter, Maria, et al.
(författare)
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Structural effects of the dispersing agent polysorbate 80 on liquid crystalline nanoparticles of soy phosphatidylcholine and glycerol dioleate
- 2015
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Ingår i: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 11:6, s. 1140-1150
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Tidskriftsartikel (refereegranskat)abstract
- Well-defined, stable and highly structured I-2 (Fd (3) over barm) liquid crystalline nanoparticles (LCNP) of 50/50 (wt/wt) soy phosphatidylcholine (SPC)/glycerol dioleate (GDO), can be formed by using a low fraction (5-10 wt%) of the dispersing polymeric surfactant polyoxyethylene (20) sorbitan monooleate (polysorbate 80 or P80). In the present study we used small angle neutron scattering (SANS) and deuterated P80 (d-P80) to determine the location and concentration of P80 within the LCNP and small angle X-ray scattering (SAXS) to reveal the internal structure. SANS data suggests that some d-P80 already penetrates the particle core at 5%. However, the content of d-P80 is still low enough not to significantly change the internal Fd (3) over barm structure of the LCNP. At higher fractions of P80 a phase separation occurs, in which a SPC and P80 rich phase is formed at the particle surface. The surface layer becomes gradually richer in both solvent and d-P80 when the surfactant concentration is increased from 5 to 15%, while the core of the particle is enriched by GDO, resulting in loss of internal structure and reduced hydration. We have used neutron reflectometry to reveal the location of the stabiliser within the adsorbed layer on an anionic silica and cationic (aminopropyltriethoxysilane (APTES) silanized) surface. d-P80 is enriched closest to the supporting surface and slightly more so for the cationic APTES surface. The results are relevant not only for the capability of LCNPs as drug delivery vehicles but also as means of preparing functional surface coatings.
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