| 1. |
- Morin, Maxim, et al.
(författare)
-
Skin hydration dynamics investigated by electrical impedance techniques in vivo and in vitro
- 2020
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 17218-
-
Tidskriftsartikel (refereegranskat)abstract
- Skin is easily accessible for transdermal drug delivery and also attractive for biomarker sampling. These applications are strongly influenced by hydration where elevated hydration generally leads to increased skin permeability. Thus, favorable transdermal delivery and extraction conditions can be easily obtained by exploiting elevated skin hydration. Here, we provide a detailed in vivo and in vitro investigation of the skin hydration dynamics using three techniques based on electrical impedance spectroscopy. Good correlation between in vivo and in vitro results is demonstrated, which implies that simple but realistic in vitro models can be used for further studies related to skin hydration (e.g., cosmetic testing). Importantly, the results show that hydration proceeds in two stages. Firstly, hydration between 5 and 10 min results in a drastic skin impedance change, which is interpreted as filling of superficial voids in skin with conducting electrolyte solution. Secondly, a subtle impedance change is observed over time, which is interpreted as leveling of the water gradient across skin leading to structural relaxation/changes of the macromolecular skin barrier components. With respect to transdermal drug delivery and extraction of biomarkers; 1 h of hydration is suggested to result in beneficial and stable conditions in terms of high skin permeability and extraction efficiency.
|
|
| 2. |
- Del Corso, M., et al.
(författare)
-
Current Knowledge and Perspectives for the Use of Platelet-Rich Plasma (PRP) and Platelet-Rich Fibrin (PRF) in Oral and Maxillofacial Surgery Part 1: Periodontal and Dentoalveolar Surgery
- 2012
-
Ingår i: Current Pharmaceutical Biotechnology. - : Bentham Science Publishers Ltd.. - 1389-2010 .- 1873-4316. ; 13:7, s. 1207-1230
-
Tidskriftsartikel (refereegranskat)abstract
- Platelet concentrates for surgical use are innovative tools of regenerative medicine, and were widely tested in oral and maxillofacial surgery. Unfortunately, the literature on the topic is contradictory and the published data are difficult to sort and interpret. In periodontology and dentoalveolar surgery, the literature is particularly dense about the use of the various forms of Platelet-Rich Plasma (PRP) - Pure Platelet-Rich Plasma (P-PRP) or Leukocyte-and Platelet-Rich Plasma (L-PRP) - but still limited about Platelet-Rich Fibrin (PRF) subfamilies. In this first article, we describe and discuss the current published knowledge about the use of PRP and PRF during tooth avulsion or extraction, mucogingival surgery, Guided Tissue Regeneration (GTR) or bone filling of periodontal intrabony defects, and regeneration of alveolar ridges using Guided Bone Regeneration (GBR), in a comprehensive way and in order to avoid the traps of a confusing literature and to highlight the underlying universal mechanisms of these products. Finally, we particularly insist on the perspectives in this field, through the description and illustration of the systematic use of L-PRF (Leukocyte-and Platelet-Rich Fibrin) clots and membranes during tooth avulsion, cyst exeresis or the treatment of gingival recessions by root coverage. The use of L-PRF also allowed to define new therapeutic principles: NTR (Natural Tissue Regeneration) for the treatment of periodontal intrabony lesions and Natural Bone Regeneration (NBR) for the reconstruction of the alveolar ridges. In periodontology, this field of research will soon find his golden age by the development of user-friendly platelet concentrate procedures, and the definition of new efficient concepts and clinical protocols.
|
|
| 3. |
- Runnsjö, Anna, et al.
(författare)
-
Diffusion through Pig Gastric Mucin : Effect of Relative Humidity
- 2016
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Mucus covers the epithelium found in all intestinal tracts, where it serves as an important protecting barrier, and pharmaceutical drugs administrated by the oral, rectal, vaginal, ocular, or nasal route need to penetrate the mucus in order to reach their targets. Furthermore, the diffusion in mucus as well as the viscosity of mucus in the eyes, nose and throat can change depending on the relative humidity of the surrounding air. In this study we have investigated how diffusion through gels of mucin, the main protein in mucus, is affected by changes in ambient relative humidity (i.e. water activity). Already a small decrease in water activity was found to give rise to a significant decrease in penetration rate through the mucin gel of the antibacterial drug metronidazole. We also show that a decrease in water activity leads to decreased diffusion rate in the mucin gel for the fluorophore fluorescein. This study shows that it is possible to alter transport rates of molecules through mucus by changing the water activity in the gel. It furthermore illustrates the importance of considering effects of the water activity in the mucosa during development of potential pharmaceuticals.
|
|
| 4. |
- Hernández, Aura Rocio, et al.
(författare)
-
New concepts for transdermal delivery of oxygen based on catalase biochemical reactions studied by oxygen electrode amperometry
- 2019
-
Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 306, s. 121-129
-
Tidskriftsartikel (refereegranskat)abstract
- The development of formulation concepts for improved skin tissue oxygenation, including methods for measuring oxygen (O) transport across biological barriers, are important research topics with respect to all processes that are affected by the O concentration, such as radiation therapy in oncology treatments, wound healing, and the general health status of skin. In this work we approach this topic by a novel strategy based on the antioxidative enzyme catalase, which is naturally present in the skin organ where it enables conversion of the reactive oxygen species hydrogen peroxide (HO) into O. We introduce various applications of the skin covered oxygen electrode (SCOE) as an in-vitro tool for studies of catalase activity and function. The SCOE is constructed by placing an excised skin membrane directly on an O electrode and the methodology is based on measurements of the electrical current generated by reduction of O as a function of time (i.e. chronoamperometry). The results confirm that a high amount of native catalase is present in the skin organ, even in the outermost stratum corneum (SC) barrier, and we conclude that excised pig skin (irrespective of freeze-thaw treatment) represents a valid model for ex vivo human skin for studying catalase function by the SCOE setup. The activity of native catalase in skin is sufficient to generate considerable amounts of O by conversion from HO and proof-of-concept is presented for catalase-based transdermal O delivery from topical formulations containing HO. In addition, we show that this concept can be further improved by topical application of external catalase on the skin surface, which enables transdermal O delivery from 50 times lower concentrations of HO. These important results are promising for development of novel topical or transdermal formulations containing low and safe concentrations of HO for skin tissue oxygenation. Further, our results indicate that the O production by catalase, derived from topically applied S. epidermidis (a simple model for skin microbiota) is relatively low as compared to the O produced by the catalase naturally present in skin. Still, the catalase activity derived from S. epidermidis is measurable. Taken together, this work illustrates the benefits and versatility of the SCOE as an in vitro skin research tool and introduces new and promising strategies for transdermal oxygen delivery, with simultaneous detoxification of HO, based on native or topically applied catalase.
|
|
| 5. |
- Valetti, Sabrina, et al.
(författare)
-
Can mesoporous nanoparticles promote bioavailability of topical pharmaceutics?
- 2021
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 602
-
Tidskriftsartikel (refereegranskat)abstract
- When applied to skin, particulate matter has been shown to accumulate in hair follicles. In addition to follicles, the skin topography also incorporates trench-like furrows where particles potentially can accumulate; however, the furrows have not been as thoroughly investigated in a drug delivery perspective. Depending on body site, the combined follicle orifices cover up to 10% of the skin surface, while furrows can easily cover 20%, reaching depths exceeding 25 mu m. Hence, porous particles of appropriate size and porosity could serve as carriers for drugs to be released in the follicles prior to local or systemic absorption. In this paper, we combine multiphoton microscopy, scanning electron microscopy, and Franz cell diffusion technology to investigate ex-vivo skin accumulation of mesoporous silica particles (average size of 400-600 nm, 2, and 7 mu m, respectively), and the potential of which as vehicles for topical delivery of the broad-spectrum antibiotic metronidazole. We detected smaller particles (400-600 nm) in furrows at depths of about 25 mu m, also after rinsing, while larger particles (7 mu m) where located more superficially on the skin. This implies that appropriately sized porous particles may serve as valuable excipients in optimizing bioavailability of topical formulations. This work highlights the potential of skin furrows for topical drug delivery.
|
|
| 6. |
- Johansson Östbring, Malin, 1980-, et al.
(författare)
-
Effects of a pharmaceutical care intervention on clinical outcomes and patient adherence in coronary heart disease : the MIMeRiC randomized controlled trial
- 2021
-
Ingår i: BMC Cardiovascular Disorders. - : BioMed Central. - 1471-2261 .- 1471-2261. ; 21:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the treatment of coronary heart disease, secondary prevention goals are still often unmet and poor adherence to prescribed drugs has been suggested as one of the reasons. We aimed to investigate whether pharmaceutical care by a pharmacist at the cardiology clinic trained in motivational interviewing improves clinical outcomes and patient adherence.METHODS: This was a prospective, randomized, controlled, outcomes-blinded trial designed to compare pharmaceutical care follow-up with standard care. After standard follow-up at the cardiology clinic, patients in the intervention group were seen by a clinical pharmacist two to five times as required over seven months. Pharmacists were trained to use motivational interviewing in the consultations and they tailored their support to each patient's clinical needs and beliefs about medicines. The primary study end-point was the proportion of patients who reached the treatment goal for low-density lipoprotein cholesterol by 12 months after discharge. The key secondary outcome was patient adherence to lipid-lowering therapy at 15 months after discharge, and other secondary outcomes were the effects on patient adherence to other preventive drugs, systolic blood pressure, disease-specific quality of life, and healthcare use.RESULTS: 316 patients were included. The proportion of patients who reached the target for low-density lipoprotein cholesterol were 37.0% in the intervention group and 44.2% in the control group (P = .263). More intervention than control patients were adherent to cholesterol-lowering drugs (88 vs 77%; P = .033) and aspirin (97 vs 91%; P = .036) but not to beta-blocking agents or renin-angiotensin-aldosterone system inhibitors.CONCLUSIONS: Our intervention had no positive effects on risk factors for CHD, but it increased patient adherence. Further investigation of the intervention process is needed to explore the difference in results between patient adherence and medication effects. Longer follow-up of healthcare use and mortality will determine if the increased adherence per se eventually will have a meaningful effect on patient health.TRIAL REGISTRATION: ClinicalTrials.gov NCT02102503, 03/04/2014 retrospectively registered.
|
|
| 7. |
- Pham, Quoc Dat, et al.
(författare)
-
Chemical penetration enhancers in stratum corneum : Relation between molecular effects and barrier function
- 2016
-
Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 232, s. 175-187
-
Tidskriftsartikel (refereegranskat)abstract
- Skin is attractive for drug therapy because it offers an easily accessible route without first-pass metabolism. Transdermal drug delivery is also associated with high patient compliance and through the site of application, the drug delivery can be locally directed. However, to succeed with transdermal drug delivery it is often required to overcome the low permeability of the upper layer of the skin, the stratum corneum (SC). One common strategy is to employ so-called penetration enhancers that supposedly act to increase the drug passage across SC. Still, there is a lack of understanding of the molecular effects of so-called penetration enhancers on the skin barrier membrane, the SC. In this study, we provide a molecular characterization of how different classes of compounds, suggested as penetration enhancers, influence lipid and protein components in SC. The compounds investigated include monoterpenes, fatty acids, osmolytes, surfactant, and Azone. We employ natural abundance C-13 polarization transfer solid-state nuclear magnetic resonance (NMR) on intact porcine SC. With this method it is possible to detect small changes in the mobility of the minor fluid lipid and protein SC components, and simultaneously obtain information on the major fraction of solid SC components. The balance between fluid and solid components in the SC is essential to determine macroscopic material properties of the SC, including barrier and mechanical properties. We study SC at different hydration levels corresponding to SC in ambient air and under occlusion. The NMR studies are complemented with diffusion cell experiments that provide quantitative data on skin permeability when treated with different compounds. By correlating the effects on SC molecular components and SC barrier function, we aim at deepened understanding of diffusional transport in SC, and how this can be controlled, which can be utilized for optimal design of transdermal drug delivery formulations. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license.
|
|
| 8. |
- Jankovskaja, Skaidre, et al.
(författare)
-
Optimization of sample preparation for transporter protein quantification in tissues by LC–MS/MS
- 2019
-
Ingår i: Journal of Pharmaceutical and Biomedical Analysis. - : Elsevier BV. - 0731-7085 .- 1873-264X. ; 164, s. 9-15
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Reproducible quantification of drug transporter protein expression in tissues is important for predicting transporter mediated drug disposition. Many mass-spectrometry based transporter protein quantification methods result in high variability of the estimated transporter quantities. Therefore, we aimed to evaluate and optimize mass spectrometry-based quantification method for drug transporter proteins in tissues. Materials and methods: Plasma membrane (PM) proteins from mouse tissues were isolated by applying three extraction protocols: commercial plasma membrane extraction kit, tissue homogenization by Potter-Elvehjem homogenizer in combination with sucrose-cushion ultracentrifugation, and PM enrichment with Tween 40. Moreover, five different protein digestion protocols were applied on the same PM fraction. PM isolation and digestion protocols were evaluated by measuring the amount of transporter proteins by liquid chromatography-tandem mass spectrometry in selected reaction monitoring mode. Results: Mouse liver homogenization by Potter-Elvehjem homogenizer in combination with sucrose-cushion ultracentrifugation and PM enrichment with Tween 40 resulted in two times higher transporter protein quantity (Breast cancer resistance protein (Bcrp) 18.0 fmol/μg protein) in comparison with the PM samples isolated by extraction kit (Bcrp 9.8 fmol/μg protein). The evaluation of protein digestion protocols revealed that the most optimal protocol for PM protein digestion is with Lys-C and trypsin, in combination with trypsin enhancer and heat denaturation. Overall, quantities of Bcrp and Na+/K + ATPase proteins evaluated in mouse liver and kidney cortex by using our optimized PM isolation method, as well as, established digestion protocol were two to three times higher than previously reported and coefficient of variation (CV) for technical replicates was below 10%. Conclusion: We have established an improved transporter protein quantification methodology by optimizing PM isolation and protein digestion procedures. The optimized procedure resulted in a higher transporter protein yield and improved precision.
|
|
| 9. |
|
|
| 10. |
- Valetti, Sabrina, et al.
(författare)
-
Oral transmucosal delivery of eletriptan for neurological diseases
- 2022
-
Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 627, s. 122222-
-
Tidskriftsartikel (refereegranskat)abstract
- Migraine is a highly prevalent neurological disease affecting circa 1 billion patients worldwide with severe incapacitating symptoms, which significantly diminishes the quality of life. As self-medication practice, oral administration of triptans is the most common option, despite its relatively slow therapeutic onset and low drug bioavailability. To overcome these issues, here we present, to the best of our knowledge, the first study on the possibility of oral transmucosal delivery of one of the safest triptans, namely eletriptan hydrobromide (EB). Based on a comprehensive set of in vitro and ex vivo experiments, we highlight the conditions required for oral transmucosal delivery, potentially giving rise to similar, or even higher, drug plasma concentrations expected from conventional oral administration. With histology and tissue integrity studies, we conclude that EB neither induces morphological changes nor impairs the integrity of the mucosal barrier following 4 h of exposure. On a cellular level, EB is internalized in human oral keratinocytes within the first 5 min without inducing toxicity at the relevant concentrations for transmucosal delivery. Considering that the pKa of EB falls within the physio-logically range, we systematically investigated the effect of pH on both solubility and transmucosal permeation. When the pH is increased from 6.8 to 10.4, the drug solubility decreases drastically from 14.7 to 0.07 mg/mL. At pH 6.8, EB gave rise to the highest drug flux and total permeated amount across mucosa, while at pH 10.4 EB shows greater permeability coefficient and thus higher ratio of permeated drug versus applied drug. Permeation experiments with model membranes confirmed the pH dependent permeation profile of EB. The distribution of EB in different cellular compartments of keratinocytes is pH dependent. In brief, high drug ionization leads to higher association with the cell membrane, suggesting ionic interactions between EB and the phospholipid head groups. Moreover, we show that the chemical permeation enhancer DMSO can be used to enhance the drug permeation significantly (i.e., 12 to 36-fold increase). Taken together, this study presents important findings on transmucosal delivery of eletriptan via the oral cavity and paves the way for clinical investigations for a fast and safe migraine treatment.
|
|
