E Björk

Uppsala University, Uppsala, Uppsala, Sweden

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Publications (56)219.35 Total impact

  • Noel Dew, Katarina Edsman, Erik Björk
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    ABSTRACT: The aim of this study was to investigate skin permeation rates of a drug substance when applied in novel gel formulations with catanionic aggregates. Reference gel without catanionic aggregates was compared with formulations with catanionic aggregates composed of tetracaine and either sodium dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare the effect of different gel types to elucidate if physically cross-linked, 'self-destructing' systems had benefits compared with classical, covalently cross-linked, gels. The rheological investigation showed that the interactions between the SoftCAT polymer and tetracaine/SDS aggregates were stronger than when the tetracaine/capric acid aggregates were used. The skin permeation was measured ex vivo in horizontal Ussing chambers and the permeation of tetracaine was significantly lower when formulations with tetracaine/SDS aggregates were applied (P < 0.001), but not statistically different from the reference when capric acid was used. No morphological differences could be distinguished between the skin samples exposed to the different formulations or the reference. Skin permeation was compared with silicone sheet permeation and the results indicated that silicone sheets could be used as a model of skin when using these formulations.
    The Journal of pharmacy and pharmacology. 10/2011; 63(10):1265-73.
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    ABSTRACT: To fully utilize the extended contact time of gel formulations a novel formulation with drug containing catanionic aggregates offering prolonged drug release and skin penetration were investigated. This study aimed to further explore the drug release process from catanionic vesicles in gels. Catanionic vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels composed of catanionic vesicles and a SoftCAT polymer were used as well as covalent Carbopol gels. Drug release was measured in vitro using a modified USP paddle method and the skin penetration was studied using dermatomized pig ear skin mounted in horizontal Ussing chambers. The aggregate structure was visualized with cryo-TEM during the drug release and skin penetration process. The study results show that catanionic vesicles are present in the formulations throughout the drug release process and during the clinically relevant skin application time. Hence, the decreased skin penetration rate stems from the prolonged release of drug substance from the gels. The rheological investigation shows that the gel structure of the physically cross-linked gels is maintained even as the drug substance is released and the gel volume is decreased. These findings indicate that the applicability of formulations like these is a future possibility.
    Colloids and surfaces B: Biointerfaces 09/2011; 89:53-60. · 4.28 Impact Factor
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    ABSTRACT: After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon. Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA(1c) , plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose ≤ 0.3 U kg(-1) 24 h(-1) and HbA(1c) within the normal range, in relation to the above-mentioned variables. A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin/C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.
    Diabetic Medicine 02/2011; 28(2):156-61. · 3.24 Impact Factor
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    ABSTRACT: To create improved pharmaceutical formulations for nasal and sublingual administration of desmopressin and investigate their pharmacokinetic profiles in comparison with a commercial nasal liquid spray and finally to evaluate the volunteers' opinions on the different dosage forms. Both formulations were based on the characteristics of interactive mixtures. The nasal powder spray was produced by a rotary evaporator technique with sodium starch glycolate as carrier material and the sublingual tablet by direct compression after dry mixing with mannitol as carrier. The clinical study was an open-label, randomised cross-over pharmacokinetic study in healthy volunteers. The nasal powder formulation gave a threefold increase in the absorption, unaltered time to maximum plasma concentration and a tendency to lower variability in the amount absorbed compared with the liquid spray. The powder was reported to be more irritating than the liquid but was still well accepted by the volunteers. The tablet did not improve the uptake of desmopressin, likely because of a poor disintegration sublingually. The nasal powder formulation is a promising new dosage form for the delivery of desmopressin and other compounds. The sublingual tablet has a beneficial means of production and may be further developed by decreasing its disintegration time.
    Pharmaceutical Research 04/2009; 26(7):1618-25. · 4.74 Impact Factor
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    ABSTRACT: We have evaluated the interactions between superdisintegrants and drugs with different physicochemical characteristics, which may affect the in-vivo absorption e.g. after mucosal administration. The binding of sodium salicylate, naproxen, methyl hydroxybenzoate (methylparaben), ethyl hydroxybenzoate (ethylparaben), propyl hydroxybenzoate (propylparaben), atenolol, alprenolol, diphenhydramine, verapamil, amitriptyline and cetylpyridinium chloride monohydrate (CPC) to different superdisintegrants (sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone) and one unsubstituted comparator (starch) was studied spectrophotometrically. An indication of the in-vivo effect was obtained by measuring the interactions at physiological salt concentrations. SSG was investigated more thoroughly to obtain release profiles and correlation between binding and ionic strength. The results showed that the main interactions with the anionic hydrogels formed by SSG and CCS were caused by ion exchange, whereas the neutral crospovidone exhibited lipophilic interactions with the non-ionic substances. The effect of increased ionic strength was most pronounced at low salt concentrations and the ion exchange interactions were almost completely eradicated at physiological conditions. The release profile of diphenhydramine was significantly affected by the addition of salt. It was thus concluded that the choice of buffer was of great importance for in-vitro experiments with ionic drugs. At physiological salt concentrations the interactions did not appear to be strong enough to influence the in-vivo bioavailability of any of the drug molecules.
    Journal of Pharmacy and Pharmacology 01/2009; 60(12):1583-9. · 2.03 Impact Factor
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    ABSTRACT: The residence time in the nasal cavity can be prolonged by dry particles that absorb water and subsequently increase the viscosity of the mucus layer. A novel nasal drug delivery system based on interactive mixtures has previously been developed, where fine particles of the active component are adhered to the surface of mucoadhesive carrier particles by dry mixing. The surface coverage may alter the original mucoadhesiveness of the carrier particles and to investigate this, a simplified tensile strength method was developed and evaluated. Reliable results were obtained with a plastic coated absorbent paper covered by a mucin solution as a substitution for porcine nasal mucosa and should also be applicable to other dry particle systems. The method showed that the swelling of sodium starch glycolate particles was slightly delayed, corresponding to the degree of hydrophobic surface coverage. Carrier particles of partly pregelatinized maize starch were not influenced by the addition of a hydrophobic substance, probably because of the rough particle shape that inhibited a complete surface coverage. It was concluded that the surface coverage of carrier particles in interactive mixtures only could cause a short delay in water absorption that should not affect their mucoadhesive characteristics in vivo.
    Journal of Pharmaceutical Sciences 02/2008; 97(9):3855-64. · 3.13 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether mucoadhesive interactive mixtures can be created using carrier particles in a size range appropriate for nasal administration, i.e. 10-50 microm. We also used theoretical models to investigate if homogeneity measurements can be used to evaluate the formation of interactive mixtures containing carrier particles in this size range. Sodium starch glycolate (SSG) was used as carrier material and sodium salicylate (SS) as the model fine-particulate drug. The size ranges of SSG particles and amounts of SS were varied to find the smallest carrier particle size and highest amount of drug that still resulted in an interactive mixture. Visual inspection of the mixtures by scanning electron microscopy showed that interactive mixtures could be formed with carrier particles as small as 30 microm and containing up to 4% (w/w) of SS. Comparisons with theoretical models highlighted the difficulties of using homogeneity measurements to determine if interactive mixtures were formed. The measured coefficients of variation (CV) for the amount of drug in the samples were low and inferior mixtures were associated with only a slight increase. It was thus concluded that mucoadhesive interactive mixtures can be created in an appropriate size range for nasal administration, but that visual inspection of these mixtures is initially necessary to confirm the formation of an interactive mixture.
    European Journal of Pharmaceutics and Biopharmaceutics 10/2007; 67(2):370-6. · 3.83 Impact Factor
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    ABSTRACT: The aim of this study was to quantify the olfactory transfer of morphine to the brain hemispheres by comparing brain tissue and plasma morphine levels after nasal administration with those after intravenous administration. Morphine (1.0 mg/kg body weight) was administered via the right nostril or intravenously as a 15-min constant-rate infusion to male rats. The content of morphine and its metabolite morphine-3-glucuronide in samples of the olfactory bulbs, brain hemispheres, and plasma was assessed using high-performance liquid chromatography, and the areas under the concentration-time curves (AUC) were calculated. At both 5 and 15 min after administration, brain hemisphere morphine concentrations after nasal administration were similar to those after i.v. administration of the same dose, despite lower plasma concentrations after nasal administration. The brain hemispheres/plasma morphine AUC ratios for the 0-5 min period were thus approximately 3 and 0.1 after nasal and i.v. administration, respectively, demonstrating a statistically significant early distribution advantage of morphine to the brain hemispheres via the nasal route. Morphine is transferred via olfactory pathways to the brain hemispheres, and drug transfer via this route significantly contributes to the early high brain concentrations after nasal administration to rats.
    Pharmaceutical Research 04/2006; 23(3):565-72. · 4.74 Impact Factor
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    ABSTRACT: To study the impact of blood glucose concentrations on early stroke mortality in diabetic and non-diabetic stroke patients, and to identify the optimal blood glucose concentration for each patient category. A representative sample of 81 diabetic and 366 non-diabetic stroke patients was studied. Logistic regression analyses were performed in order to estimate the impact of blood glucose concentrations on admission and during hospital stay and other clinical parameters on 30-day case-fatality. Receiver operating characteristic curves were used to predict case-fatality by blood glucose. Blood glucose, body temperature and level of consciousness were independently related to early stroke mortality in diabetic and non-diabetic patients. The mean blood glucose concentration had a greater impact on 30-day case-fatality than the admission blood glucose, particularly in diabetic patients. A mean blood glucose concentration above 10.3 mmol/l predicted 30-day case-fatality in diabetic patients. The corresponding value was 6.3 mmol/l in non-diabetic patients. Improved blood glucose control has a potential to reduce early stroke mortality. The optimal glucose concentration seems to be higher in diabetic than in non-diabetic patients.
    Acta Neurologica Scandinavica 09/2005; 112(2):81-7. · 2.47 Impact Factor
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    ABSTRACT: The cell toxic effects of nonionic surfactants were investigated by means of two in vitro models, namely pig nasal mucosa mounted in horizontal Ussing chambers, and Caco-2 cell monolayers. A series of homologous polyethyleneoxide (PEO) surfactants with a wide span in hydrophilic head-group size and hydrophobic chain lengths were screened for concentration-dependent effects on the transepithelial electrical resistance (TEER) and mannitol permeability across Caco-2 cell monolayers. Trends in effects on permeability in the presence of increasing surfactant concentration coincided with the effects seen on TEER. Correlation of surfactant molecular structure with cell toxicity showed the size of the PEO group to be a more critical parameter than the size of the hydrocarbon chain. More specifically, the presence of very long PEO groups (>30 EO units) were found to lead to a decrease in cell toxicity. Similar trends were observed in the studies of the effects of PEO surfactants on pig nasal mucosa mounted in horizontal Ussing chambers. However, the nasal mucosa was somewhat more tolerant towards high surfactant concentrations than the Caco-2 cells. The relation between surfactant molecular structure and cell toxic effects is discussed in terms of micellar surface adsorption and micellar solubilization. The effect of the surfactants on the solubility of budesonide was investigated at two different surfactant concentrations (0.01 and 1 mg/mL). At the lower concentration, the solubilizing capacity of all of the surfactants was marginal, and there was no correlation between solubilizing capacity and cmc. At the higher concentration, on the other hand, all surfactants substantially increased the solubility of budesonide. The C18 PEO-ester with 40 EO units in the head group was found to be an efficient micellar solubilizer for budesonide, without causing adverse effects on the Caco-2 cell monolayers.
    Journal of Pharmaceutical Sciences 05/2005; 94(4):730-44. · 3.13 Impact Factor
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    ABSTRACT: The aim of this study was to investigate whether morphine can be transferred along the olfactory pathway to the CNS, thereby circumventing the blood-brain barrier, after nasal administration to rodents. Radiolabelled and unlabelled morphine were administered via the right nostril to mice and rats. Olfactory bulbs, brain tissue and blood samples were collected. Morphine-derived radioactivity was measured using liquid scintillation (LS) and the concentrations of morphine and its metabolite morphine-3-glucuronide (M3G) were also assessed with high-performance liquid chromatography. The location of morphine-derived radioactivity in the rat brain was visualised by autoradiography. Overall, the levels of morphine in the right olfactory bulbs (ROBs) significantly exceeded those in the left olfactory bulbs (LOBs) and brain tissue samples 15, 60 and 240 min after right-sided nasal administration. Fifteen minutes after intravenous administration, there were no significant differences between olfactory bulbs and the other brain areas. Five minutes after nasal administration, autoradiography revealed radioactivity surrounding the ROB and reaching one of the ventricles in the brain. After 60 min, radioactivity had reached the peripheral parts of the ROB. All the techniques used in this study demonstrate that morphine was transferred along the olfactory pathway to the CNS after nasal administration to rodents.
    European Journal of Pharmaceutical Sciences 05/2005; 24(5):565-73. · 2.99 Impact Factor
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    ABSTRACT: The nasal uptake of a 3000 Da fluorescein dextran (FD3) was investigated in rats, using fluorescence microscopy. The uptake from a formulation containing deacetylated gellan gum, an in situ gelling agent, was compared to that from a mannitol solution. Additionally, the rheological behavior of the gellan gum in water and saline was studied. It was shown that the gellan gum solution was easily administered owing to its low viscosity, and upon contact with the mucosa, a gel was formed. The epithelial uptake and transfer of FD3 appeared to be increased and prolonged using the gellan gum formulation. This increase was not accompanied by qualitative changes of the epithelial FD3 distribution or any visible harmful effects.
    European Journal of Pharmaceutics and Biopharmaceutics 05/2005; 59(3):557-64. · 3.83 Impact Factor
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    ABSTRACT: To investigate whether measurements of proinsulin and/or intermediate proinsulin degradation products could be used to differentiate between autoimmune (type 1) and non-autoimmune (type 2) diabetes in young adults. Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were measured in 25 patients aged 15-34 years with type 1 diabetes, as defined by the presence of at least two positive islet autoantibodies, and in 23 antibody-negative patients of similar age with type 2 diabetes, at the time of clinical onset of diabetes and at 3-4 months thereafter. Comparisons were made with data from 25 healthy subjects matched for gender and age. Plasma levels of total proinsulin, intact proinsulin and 32,33 split proinsulin were significantly increased 2-3-fold in the patients with newly diagnosed type 2 diabetes as compared with the controls, both in absolute terms (p<0.0001) and when related to circulating insulin (p<0.01-0.0002). In contrast, absolute proinsulin and 32,33 split proinsulin concentrations were significantly lower in patients with onset of type 1 diabetes than in controls. When proinsulin and split proinsulin release were related to plasma insulin, however, similar ratios were found in the type 1 diabetes patients and in controls. Using the 90th percentile for total proinsulin in the control group as the cut-off, the sensitivity and specificity for differentiation between autoimmune and non-autoimmune diabetes were 87% and 92%, respectively. At 3-4 months after clinical onset of diabetes, proinsulin secretion was still 2-3 times higher in type 2 than in type 1 diabetes patients (p<0.001). Young adult patients with newly diagnosed type 2 diabetes display disproportionate hyperproinsulinemia, whereas proinsulin secretion appears to be normal in patients with clinical onset of type 1 diabetes. Evaluation of proinsulin and 32,33 split proinsulin concentrations may be useful as a diagnostic tool in differentiating between autoimmune and non-autoimmune diabetes in young adults, particularly in those lacking islet autoantibodies at diagnosis.
    Scandinavian Journal of Clinical and Laboratory Investigation 01/2005; 65(7):585-94. · 1.29 Impact Factor
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    ABSTRACT: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA(1c) and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose </= 0.3 U/kg/24 h and HbA(1c) within the normal range, was analysed in relation to characteristics at diagnosis. Remissions were seen in 43% of the patients with a median duration of 8 months (range 1-73). Sixteen per cent had a remission with a duration > 12 months. Among patients with antibodies (ab(+)), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m(2)) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab(+) remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.
    Diabetic Medicine 05/2004; 21(5):447-55. · 3.24 Impact Factor
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    ABSTRACT: To establish the prevalence of remaining beta-cell function 8 years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8 years later. Population-based cohort study. Nationwide from all Departments of Medicine and Endocrinology in Sweden. A total of 312 young (15-34 years old) adults diagnosed with diabetes during 1987-88. Plasma connecting peptide (C-peptide) 8 years after diagnosis. Preserved beta-cell function was defined as measurable C-peptide levels. Three islet antibodies - cytoplasmic islet cell antibodies (ICA), glutamic acid decarboxylase antibodies and tyrosine phosphatase antibodies - were measured. Amongst 269 islet antibody positives (ab+) at diagnosis, preserved beta-cell function was found in 16% (42/269) 8 years later and these patients had a higher body mass index (median 22.7 and 20.5 kg m-2, respectively; P = 0.0003), an increased frequency of one islet antibody (50 and 24%, respectively; P = 0.001), and a lower prevalence of ICA (55 and 6%, respectively; P = 0.007) at diagnosis compared with ab+ without remaining beta-cell function. Amongst the 241 patients without detectable beta-cell function at follow-up, 14 lacked islet antibodies, both at diagnosis and at follow-up. Sixteen per cent of patients with autoimmune type 1 diabetes had remaining beta-cell function 8 years after diagnosis whereas 5.8% with beta-cell failure lacked islet autoimmunity, both at diagnosis and at follow-up.
    Journal of Internal Medicine 04/2004; 255(3):384-91. · 6.46 Impact Factor
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    ABSTRACT: To study trends in body mass index (BMI) at diagnosis of diabetes in all young Swedish adults in the age range of 15-34 years registered in a nation-based registry. The BMI was assessed at diagnosis in diabetic patients 15-34 years of age at diagnosis, for a period of 17 years (1983-1999). Islet cell antibodies (ICA) were measured during three periods (1987-1988, 1992-1993 and 1998-1999). A nationwide study (Diabetes Incidence Study in Sweden). A total of 4727 type 1 and 1083 type 2 diabetic patients. Incidence-year specific BMI adjusted for age, gender and time of diagnosis (month). Body mass index at diagnosis increased significantly both in type 1 (21.4 +/- 3.6 to 22.5 +/- 4.0; P < 0.0001) and in type 2 (27.4 +/- 6.8 to 32.0 +/- 6.0; P < 0.0001) diabetic patients, also when adjusted for age, gender and month of diagnosis. A similar significant increase in BMI was found in type 1 diabetic patients and in type 2 diabetic patients in the periods 1987-1988, 1992-1993 and 1998-1999; years when ICA were assessed and considered in the classification of diabetes. Despite this increase in BMI, there was no increase in the incidence of diabetes in young-adult people in Sweden. Body mass index at diagnosis of diabetes in subjects 15-34 years of age has substantially increased during 1983-1999 in Sweden when adjusted for age, gender and month of diagnosis.
    Journal of Internal Medicine 09/2003; 254(3):251-6. · 6.46 Impact Factor
  • Cecilia Wadell, Erik Björk, Ola Camber
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    ABSTRACT: The Ussing chamber diffusion system was used as a model to study the apparent permeability across porcine nasal mucosa of eight drugs and molecules with different physicochemical characteristics, namely insulin, lidocaine, nicotine, PEG 4000, propranolol, sumatriptan, melagatran and an amino diether. A weak correlation was found between the apparent permeability coefficients and the corresponding literature data on the fraction absorbed after nasal administration in humans. In the case of passively transported drugs, a closer correlation was found than for the substances where other mechanisms such as carrier-mediated transport or possible efflux were involved. Factors influencing the correlation between in vitro and in vivo data are discussed and the importance of electrophysiological control of the viability status of the excised mucosa is emphasised. Although caution has to be exercised in view of the limitations of the in vitro system, it seems to be a useful tool when evaluating different factors influencing permeability of nasal mucosa.
    European Journal of Pharmaceutical Sciences 02/2003; 18(1):47-53. · 2.99 Impact Factor
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    ABSTRACT: The uptake of ovalbumin-conjugated starch microparticles (OVA-MP) was studied after application to porcine respiratory nasal mucosa in vitro. Nasal mucosa from freshly slaughtered pigs was mounted in horizontal Ussing chambers, which permit monitoring of the viability of the tissue exposed to microparticles and ensure that the microparticles are deposited on the mucosa. The antigen-conjugated starch microparticles have previously been shown to produce strong mucosal, cellular and systemic immune responses to conjugated model antigens following oral administration. Intranasal administration of vaccines for mucosal immunisation is an interesting alternative to oral administration, since nasal delivery systems generally require lower doses of antigen and the site of application is better suited for protection against air-borne antigens. Most of a nasally administered dose is deposited on the surface of the respiratory area of the nasal mucosa. It is therefore important to examine whether the microparticles are taken up in this area and, if so, by which cell type. Confocal laser scanning microscopy and transmission electron microscopy (TEM) of the nasal tissue both showed intracellular OVA-MP in non-ciliated epithelial cells after 45 min' incubation. The morphology of the cells in the TEM preparations did not support the presence of either M cells (specialised antigen sampling cells) or adjacent lymphocytes. Anticytokeratin-18 (Ac18) was used as a potential M cell marker. However, there was no indication of Ac18 binding to M cells, but it did bind to mucus-producing cells in the respiratory nasal mucosa. In conclusion, OVA-MP were taken up intracellularly by non-ciliated epithelial cells in the nasal respiratory mucosa of pigs, in vitro.
    Journal of Drug Targeting 02/2003; 11(1):75-82. · 2.77 Impact Factor
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    ABSTRACT: We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (<0.25 nmol/l) at follow-up. Most young adults with clinical Type 1 diabetes (199/218, 91%) had objective Type 1 (ab+ at diagnosis/follow-up and/or low fasting plasma C-peptide concentrations at follow-up), as did one third (18/58, 31%) with clinical Type 2 diabetes and more than half (22/37, 59%) with unclassifiable diabetes. About 10% of those who were antibody negative converted to antibody positive. Our study underlines that a classification considering aetiology is superior to clinical judgement.
    Diabetologia 02/2003; 46(2):173-81. · 6.49 Impact Factor
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    ABSTRACT: In this study, controlled release gel formulations containing dihydroalprenolol (DHA), hydrocortisone (HC) or testosterone (TS) in Carbopol 934P (C934) were evaluated using pig nasal mucosa in a horizontal Ussing chamber. The controlled release gel formulations were designed by including DHA in vesicle bilayers formed with sodium dodecyl sulphate (SDS) (1.4 and 36 mM) and by partitioning TS to the core of Brij 58 (B58, 1%) micelles. For comparison, unmodified gels and solutions of the drugs and additives were examined in parallel experiments. The viability and toxicity were evaluated with electrophysiological measurements and light microscopy. The results showed that C934 did not affect the viability of the mucosa and that the rate and profile of the appearance on the receiver side was independent of whether the substances were released from an unmodified gel or an unmodified solution. Continuous electrophysiological measurements made during exposure showed that B58 (1%) and SDS (1.4 mM) inactivated the mucosa, whereas SDS (36 mM) activated it. Investigations made after a 90-min exposure to the formulations showed that all the modified gels had inactivated the mucosa and had negative effects on the morphology. For the TS-B58 (1%) and the DHA-SDS (36 mM) gels, the rate-limiting step in transport was the release from the formulation. The results confirmed that gels from C934 are suitable for nasal administration and also clearly indicated the different degrees of toxicity of the controlled release formulations evaluated in this study. The horizontal Ussing chamber method was a suitable tool for the evaluation of gels for nasal administration.
    Journal of Controlled Release 11/2002; 83(3):377-88. · 7.63 Impact Factor

Publication Stats

1k Citations
219.35 Total Impact Points


  • 1988–2011
    • Uppsala University
      • • Department of Medical Sciences
      • • Department of Pharmacy
      Uppsala, Uppsala, Sweden
  • 2005
    • Karolinska Institutet
      • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 1989–2004
    • Uppsala University Hospital
      • • Department of Hospital School
      • • Department of Internal Medicine
      Uppsala, Uppsala, Sweden
  • 2003
    • Malmö University
      Malmö, Skåne, Sweden
  • 2001
    • Lund University
      Lund, Skåne, Sweden