18 research outputs found
Silica nanoparticles in transmucosal drug delivery
Transmucosal drug delivery includes the administration of drugs via various mucous membranes, such as gastrointestinal, nasal, ocular, and vaginal mucosa. The use of nanoparticles in transmucosal drug delivery has several advantages, including the protection of drugs against the harsh environment of the mucosal lumens and surfaces, increased drug residence time, and enhanced drug absorption. Due to their relatively simple synthetic methods for preparation, safety profile, and possibilities of surface functionalisation, silica nanoparticles are highly promising for transmucosal drug delivery. This review provides a description of silica nanoparticles and outlines the preparation methods for various core and surface-functionalised silica nanoparticles. The relationship between the functionalities of silica nanoparticles and their interactions with various mucous membranes are critically analysed. Applications of silica nanoparticles in transmucosal drug delivery are also discussed
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Synthesis of thiolated, PEGylated and POZylated silica nanoparticles and evaluation of their retention on rat intestinal mucosa in vitro
In this study, we synthesised thiolated silica nanoparticles using 3-mercaptopropyltrimethoxysilane and functionalised them with either 5 kDa methoxy polyethylene glycol maleimide (PEG) or 5 kDa alkyne-terminated poly(2-ethyl-2-oxazoline) (POZ). The main objectives of this study are to investigate the effects of pH on the size and ξ-potential of these nanoparticles and evaluate their mucoadhesive properties ex vivo using rat intestinal mucosa. The sizes of thiolated, PEGylated and POZylated silica nanoparticles were 53 ± 1, 68 ± 1 and 59 ± 1 nm, respectively. The size of both thiolated and POZylated nanoparticles significantly increased at pH ≤ 2, whereas no size change was observed at pH 2.5–9 for both these two types of nanoparticles. On the other hand, the size of PEGylated nanoparticles did not change over the studied pH range (1.5–9). Moreover, thiolated nanoparticles were more mucoadhesive in the rat small intestine than both PEGylated and POZylated nanoparticles. After 12 cycles of washing (with a total of 20 mL of phosphate buffer solution pH 6.8), a significantly greater amount of thiolated nanoparticles remained on the intestinal mucosa than FITC-dextran (non-mucoadhesive polymer, p  0.1 for both). Thus, this study indicates that thiolated nanoparticles are mucoadhesive, whereas PEGylated and POZylated nanoparticles are non-mucoadhesive in the ex vivo rat intestinal mucosa model. Each of these nanoparticles has potential applications in mucosal drug delivery
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Metabolic Profiling of Children Undergoing Surgery for Congenital Heart Disease.
OBJECTIVE: Inflammation and metabolism are closely interlinked. Both undergo significant dysregulation following surgery for congenital heart disease, contributing to organ failure and morbidity. In this study, we combined cytokine and metabolic profiling to examine the effect of postoperative tight glycemic control compared with conventional blood glucose management on metabolic and inflammatory outcomes in children undergoing congenital heart surgery. The aim was to evaluate changes in key metabolites following congenital heart surgery and to examine the potential of metabolic profiling for stratifying patients in terms of expected clinical outcomes. DESIGN: Laboratory and clinical study. SETTING: University Hospital and Laboratory. PATIENTS: Of 28 children undergoing surgery for congenital heart disease, 15 underwent tight glycemic control postoperatively and 13 were treated conventionally. INTERVENTIONS: Metabolic profiling of blood plasma was undertaken using proton nuclear magnetic resonance spectroscopy. A panel of metabolites was measured using a curve-fitting algorithm. Inflammatory cytokines were measured by enzyme-linked immunosorbent assay. The data were assessed with respect to clinical markers of disease severity (Risk Adjusted Congenital heart surgery score-1, Pediatric Logistic Organ Dysfunction, inotrope score, duration of ventilation and pediatric ICU-free days). MEASUREMENTS AND MAIN RESULTS: Changes in metabolic and inflammatory profiles were seen over the time course from surgery to recovery, compared with the preoperative state. Tight glycemic control did not significantly alter the response profile. We identified eight metabolites (3-D-hydroxybutyrate, acetone, acetoacetate, citrate, lactate, creatine, creatinine, and alanine) associated with surgical and disease severity. The strength of proinflammatory response, particularly interleukin-8 and interleukin-6 concentrations, inversely correlated with PICU-free days at 28 days. The interleukin-6/interleukin-10 ratio directly correlated with plasma lactate. CONCLUSIONS: This is the first report on the metabolic response to cardiac surgery in children. Using nuclear magnetic resonance to monitor the patient journey, we identified metabolites whose concentrations and trajectory appeared to be associated with clinical outcome. Metabolic profiling could be useful for patient stratification and directing investigations of clinical interventions.Mr. Correia is supported by the Imperial College Stratified Medicine Graduate Training Programme in Systems Medicine and Spectroscopic Profiling (STRATiGRAD). Dr. Pathan’s institution received grant support from the British Heart Foundation (research grant) and a Higher Education Funding Council for England clinical senior lecturer award. Dr. Ng received grant support from the British Heart Foundation (Researcher salary) and received support for article research from the British Heart Foundation. Dr. Jimenez consulted for Metabometrix is employed by the Imperial College London, and received support for article research from the National Institutes of Health (NIH). Her institution received grant support from the Cardiovascular Biomedical Research Institute. Dr. Macrae is employed by Royal Brompton and Harefield NHS Foundation Trust. Dr. Holmes is employed by the Imperial College London and received support for article research. Her institution received grant support from the Imperial College London (unrelated research grants in the field of metabolic medicine). The remaining authors have disclosed that they do not have any potential conflicts of interest.This is the final published version. It first appeared at http://journals.lww.com/ccmjournal/pages/articleviewer.aspx?year=9000&issue=00000&article=97295&type=abstract
Penetration Enhancement of Topical Formulations
This special issue, which is entitled “Penetration Enhancement of Topical Formulations”, presents a selection of the latest research that elucidates the challenges facing topical formulations for human skin in addition to proposing interesting solutions.[…
Poly(lactic) acid/carbon nanotube composite microneedle arrays for dermal biosensing
Minimally
invasive, reliable and low-cost in vivo biosensors that
enable real-time detection and monitoring of clinically relevant molecules
and biomarkers can significantly improve patient health care. Microneedle
array (MNA)-based electrochemical sensors offer exciting prospects
in this respect, as they can sample directly from the skin. However,
their acceptability is dependent on developing a highly scalable and
cost-effective fabrication strategy. In this work, we evaluated the
potential for polyÂ(lactic acid)/carboxyl-multiwalled carbon nanotube
(PLA/<i>f</i>-MWCNT) composites to be developed into MNAs
and their effectiveness for dermal biosensing. Our results show that
MNAs are easily made from solvent-cast nanocomposite films by micromolding.
A maximum carbon nanotube (CNT) loading of 6 wt % was attained with
the current fabrication method. The MNAs were mechanically robust,
being able to withstand axial forces up to 4 times higher than necessary
for skin insertion. Electrochemical characterization of these MNAs
by differential pulse voltammetry (DPV) produced a linear current
response toward ascorbic acid, with a limit of detection of 180 μM.
In situ electrochemical performance was assessed by DPV measurements
in ex vivo porcine skin. This showed active changes characterized
by two oxidative peaks at 0.23 and 0.69 V, as a result of the diffusion
of phosphate-buffered saline. The diagnostic potential of this waveform
was further evaluated through a burn wound model. This showed an attenuated
oxidative response at 0.69 V. Importantly, the impact of the burn
could be measured at progressive distances from the burn site. Overall,
alongside the scalable fabrication strategy, the DPV results promise
efficient electrochemical biosensors based on CNT nanocomposite MNAs
Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation
Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases
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Distribution of esterase activity in porcine ear skin, and the effects of freezing and heat separation
Porcine ear skin is widely used to study skin permeation and absorption of ester compounds, whose permeation and absorption profiles may be directly influenced by in situ skin esterase activity. Importantly, esterase distribution and activity in porcine ear skin following common protocols of skin handling and storage have not been characterised. Thus, we have compared the distribution and hydrolytic activity of esterases in freshly excised, frozen, heated and explanted porcine ear skin. Using an esterase staining kit, esterase activity was found to be localised in the stratum corneum and viable epidermis. Under frozen storage and a common heating protocol of epidermal sheet separation, esterase staining in the skin visibly diminished. This was confirmed by a quantitative assay using HPLC to monitor the hydrolysis of aspirin, in freshly excised, frozen or heated porcine ear skin. Compared to vehicle-only control, the rate of aspirin hydrolysis was approximately three-fold higher in the presence of freshly excised skin, but no different in the presence of frozen or heated skin. Therefore, frozen and heat-separated porcine ear skin should not be used to study the permeation of ester-containing permeants, in particular co-drugs and pro-drugs, whose hydrolysis or degradation can be modulated by skin esterases
A novel versatile animal-free 3D tool for rapid low-cost assessment of immunodiagnostic microneedles
Microneedle devices offer minimally invasive and rapid biomarker extraction from the skin. However, the lack of effective assessment tools for such microneedle devices can delay their development into useful clinical applications. Traditionally, the microneedle performance is evaluated i) in vivo, using animal models, ii) ex vivo, on excised human or animal skin or iii) in vitro, using homogenised solutions with the target antigen to model the interstitial fluid. In vivo and ex vivo models are considered the gold-standard approach for the evaluation of microneedle devices because of their structural composition, however they do exhibit limitations. More specifically, they have limited availability and they present batch-to-batch variations depending on the skin origin. Furthermore, their use rises ethical concerns regarding compliance with the globally accepted 3Rs principle of reducing the use of animals for research purposes. At the same time, in vitro models fail to accurately mimic the structure and the mechanical integrity of the skin tissue that surrounds the interstitial fluid. In this study, we introduce for the first time an animal-free, mechanically robust, 3D scaffold that has great potential as an accurate in vitro evaluation tool for immunodiagnostic microneedle devices. More specifically, we demonstrate, for the first time, successful extraction and detection of a melanoma biomarker (S100B) using immunodiagnostic microneedles in the 3D culture system. Melanoma cells (A375) were cultured and expanded for 35 days in the highly porous polymeric scaffold followed by in situ capture of S100B with the microneedle device. Scanning electron microscopy showed a close resemblance between the 3D scaffold and human skin in terms of internal structure and porosity. The microneedle device detected S100B in the scaffold (with a detection pattern similar to the positive controls), while the biomarker was not detected in the surrounding liquid supernatants. Our findings demonstrate the great potential of this animal-free 3D tool for rapid and low-cost evaluation of microneedle devices