Manipulation of encapsulated artificial phospholipid membranes using sub-micellar lysolipid concentrations.

Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for synthetic biology research applications. However, their practical use is often limited by their requirement to be surrounded by oil. Here we demonstrate in-situ bilayer manipulation of submillimeter, hydrogel-encapsulated droplet interface bilayers (eDIBs). Monolithic, Cyclic Olefin Copolymer/Nylon 3D-printed microfluidic devices facilitated the eDIB formation through high-order emulsification. By exposing the eDIB capsules to varying lysophosphatidylcholine (LPC) concentrations, we investigated the interaction of lysolipids with three-dimensional DIB networks. Micellar LPC concentrations triggered the bursting of encapsulated droplet networks, while at lower concentrations the droplet network endured structural changes, precisely affecting the membrane dimensions. This chemically-mediated manipulation of enclosed, 3D-orchestrated membrane mimics, facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the droplet-based construct can pose as a chemically responsive soft material for studying membrane mechanics, and drug delivery, by controlling the cargo release from artificial cell chassis.

Building programmable multicompartment artificial cells incorporating remotely activated protein channels using microfluidics and acoustic levitation.

Intracellular compartments are functional units that support the metabolism within living cells, through spatiotemporal regulation of chemical reactions and biological processes. Consequently, as a step forward in the bottom-up creation of artificial cells, building analogous intracellular architectures is essential for the expansion of cell-mimicking functionality. Herein, we report the development of a droplet laboratory platform to engineer complex emulsion-based, multicompartment artificial cells, using microfluidics and acoustic levitation. Such levitated models provide free-standing, dynamic, definable droplet networks for the compartmentalisation of chemical species. Equally, they can be remotely operated with pneumatic, heating, and magnetic elements for post-processing, including the incorporation of membrane proteins; alpha-hemolysin; and mechanosensitive channel of large-conductance. The assembly of droplet networks is three-dimensionally patterned with fluidic input configurations determining droplet contents and connectivity, whilst acoustic manipulation can be harnessed to reconfigure the droplet network in situ. The mechanosensitive channel can be repeatedly activated and deactivated in the levitated artificial cell by the application of acoustic and magnetic fields to modulate membrane tension on demand. This offers possibilities beyond one-time chemically mediated activation to provide repeated, non-contact, control of membrane protein function. Collectively, this expands our growing capability to program and operate increasingly sophisticated artificial cells as life-like materials.

Dietary alteration of n-3 and n-6 fatty acids for headache reduction in adults with migraine: randomized controlled trial.

OBJECTIVE: To determine whether dietary interventions that increase n-3 fatty acids with and without reduction in n-6 linoleic acid can alter circulating lipid mediators implicated in headache pathogenesis, and decrease headache in adults with migraine. DESIGN: Three arm, parallel group, randomized, modified double blind, controlled trial. SETTING: Ambulatory, academic medical center in the United States over 16 weeks. PARTICIPANTS: 182 participants (88% women, mean age 38 years) with migraines on 5-20 days per month (67% met criteria for chronic migraine). INTERVENTIONS: Three diets designed with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and linoleic acid altered as controlled variables: H3 diet (n=61)-increase EPA+DHA to 1.5 g/day and maintain linoleic acid at around 7% of energy; H3-L6 diet (n=61)-increase n-3 EPA+DHA to 1.5 g/day and decrease linoleic acid to ≤1.8% of energy; control diet (n=60)-maintain EPA+DHA at <150 mg/day and linoleic acid at around 7% of energy. All participants received foods accounting for two thirds of daily food energy and continued usual care. MAIN OUTCOME MEASURES: The primary endpoints (week 16) were the antinociceptive mediator 17-hydroxydocosahexaenoic acid (17-HDHA) in blood and the headache impact test (HIT-6), a six item questionnaire assessing headache impact on quality of life. Headache frequency was assessed daily with an electronic diary. RESULTS: In intention-to-treat analyses (n=182), the H3-L6 and H3 diets increased circulating 17-HDHA (log ng/mL) compared with the control diet (baseline-adjusted mean difference 0.6, 95% confidence interval 0.2 to 0.9; 0.7, 0.4 to 1.1, respectively). The observed improvement in HIT-6 scores in the H3-L6 and H3 groups was not statistically significant (-1.6, -4.2 to 1.0, and -1.5, -4.2 to 1.2, respectively). Compared with the control diet, the H3-L6 and H3 diets decreased total headache hours per day (-1.7, -2.5 to -0.9, and -1.3, -2.1 to -0.5, respectively), moderate to severe headache hours per day (-0.8, -1.2 to -0.4, and -0.7, -1.1 to -0.3, respectively), and headache days per month (-4.0, -5.2 to -2.7, and -2.0, -3.3 to -0.7, respectively). The H3-L6 diet decreased headache days per month more than the H3 diet (-2.0, -3.2 to -0.8), suggesting additional benefit from lowering dietary linoleic acid. The H3-L6 and H3 diets altered n-3 and n-6 fatty acids and several of their nociceptive oxylipin derivatives in plasma, serum, erythrocytes or immune cells, but did not alter classic headache mediators calcitonin gene related peptide and prostaglandin E2. CONCLUSIONS: The H3-L6 and H3 interventions altered bioactive mediators implicated in headache pathogenesis and decreased frequency and severity of headaches, but did not significantly improve quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT02012790.

Droplet Microfluidics for Tumor Drug-Related Studies and Programmable Artificial Cells.

Anticancer drug development is a crucial step toward cancer treatment, that requires realistic predictions of malignant tissue development and sophisticated drug delivery. Tumors often acquire drug resistance and drug efficacy, hence cannot be accurately predicted in 2D tumor cell cultures. On the other hand, 3D cultures, including multicellular tumor spheroids (MCTSs), mimic the in vivo cellular arrangement and provide robust platforms for drug testing when grown in hydrogels with characteristics similar to the living body. Microparticles and liposomes are considered smart drug delivery vehicles, are able to target cancerous tissue, and can release entrapped drugs on demand. Microfluidics serve as a high-throughput tool for reproducible, flexible, and automated production of droplet-based microscale constructs, tailored to the desired final application. In this review, it is described how natural hydrogels in combination with droplet microfluidics can generate MCTSs, and the use of microfluidics to produce tumor targeting microparticles and liposomes. One of the highlights of the review documents the use of the bottom-up construction methodologies of synthetic biology for the formation of artificial cellular assemblies, which may additionally incorporate both target cancer cells and prospective drug candidates, as an integrated "droplet incubator" drug assay platform.

Pediatric mild head trauma: is outpatient follow-up imaging necessary or beneficial?

OBJECTIVE: Pediatric traumatic brain injury (TBI) is the leading cause of death among children and is a significant cause of morbidity. However, the majority of injuries are mild (Glasgow Coma Scale score 13-15) without any need for neurosurgical intervention, and clinically significant neurological decline rarely occurs. Although the question of repeat imaging within the first 24 hours has been discussed in the past, the yield of short-term follow-up imaging has never been thoroughly described. In this paper, the authors focus on the yield of routine repeat imaging for pediatric mild TBI (mTBI) at the first clinic visit following hospital discharge. METHODS: The authors conducted a retrospective review of patients with pediatric brain trauma who had been admitted to Johns Hopkins All Children's Hospital (JHACH). Patients with mTBI were identified, and their presentation, hospital course, and imaging results were reviewed. Those pediatric patients with mTBI who had undergone no procedure during their initial admission (only conservative treatment) were eligible for inclusion in the study. Two distinct groups were identified: patients who underwent repeated imaging at their follow-up clinic visit and those who underwent only clinical evaluation. Each case was assessed on whether the follow-up imaging had changed the follow-up course. RESULTS: Between 2010 and 2015, 725 patients with TBI were admitted to JHACH. Of those, 548 patients qualified for analysis (i.e., those with mTBI who received conservative treatment without any procedure and were seen in the clinic for follow-up evaluation within 8 weeks after the trauma). A total of 392 patients had only clinic follow-up, without any diagnostic imaging study conducted as part of their clinic visit, whereas the other 156 patients underwent repeat MRI. Only 1 patient had a symptomatic change and was admitted after undergoing imaging. For 30 patients (19.2%), it was decided after imaging to continue the neurosurgical follow-up, which is a change from the institutional paradigm after mTBI. None of these patients had a change in neurological status, and all had a good functional status. All of these patients had one more follow-up in the clinic with new MRI, and none of them required further follow-up. CONCLUSIONS: Children with mTBI are commonly followed up in the ambulatory clinic setting. The authors believe that for children with mTBI, normal clinical examination, and no new symptoms, there is no need for routine ambulatory imaging since the clinical yield of such is relatively low.

Adolescent Disc Disease: Risk Factors and Treatment Success-Related Factors.

OBJECTIVE: A paucity of literature is available discussing the associated risk factors, treatment options (including the use of minimally invasive surgery), and outcomes related to lumbar disc herniation (LDH) in children. We have discussed the risk factors for disc disease among pediatric patients and evaluated the efficacy of the minimally invasive approach. METHODS: A retrospective review of pediatric patients with lumbar disc disease who had undergone microdiscectomy at our institution from 2005 to 2016 was conducted. The preoperative presentation, hospital course, postoperative course, and follow-up data (≥3 years) were reviewed. We evaluated the risk factors for LDH and the surgical outcomes for both groups. RESULTS: A total of 52 pediatric patients had undergone 61 lumbar disc surgeries for LDH in our department from 2005 to 2016. Their average age at surgery was 16.65 years. Of the 61 procedures, 48 (78.7%) had been performed via the minimally invasive spine microdiscectomy approach and 13 (21.3%) via the open microdiscectomy approach. The average body mass index for all cases was 29.3 kg/m2. The average interval to diagnosis was 7.9 months. Of the 61 cases, 21 (34.4%) had been required for patients who were competitive athletes. In addition, 15 had been for LDH related to trauma (24.6%). In 46 of the 61 cases, complete resolution of the symptoms had occurred at the 1-year follow-up visit (79.2% of minimally invasive spine microdiscectomy vs 61.5% of open microdiscectomy). CONCLUSION: Risk factors similar to those for adult LDH, such as an elevated body mass index, can be seen in the pediatric population. However, some unique risk factors such as post-traumatic LDH were found in the pediatric age group. Minimally invasive techniques are demonstrably safe and useful in this patient population.

Formation of Polarized, Functional Artificial Cells from Compartmentalized Droplet Networks and Nanomaterials, Using One-Step, Dual-Material 3D-Printed Microfluidics.

The bottom-up construction of synthetic cells with user-defined chemical organization holds considerable promise in the creation of bioinspired materials. Complex emulsions, droplet networks, and nested vesicles all represent platforms for the engineering of segregated chemistries with controlled communication, analogous to biological cells. Microfluidic manufacture of such droplet-based materials typically results in radial or axisymmetric structures. In contrast, biological cells frequently display chemical polarity or gradients, which enable the determination of directionality, and inform higher-order interactions. Here, a dual-material, 3D-printing methodology to produce microfluidic architectures that enable the construction of functional, asymmetric, hierarchical, emulsion-based artificial cellular chassis is developed. These materials incorporate droplet networks, lipid membranes, and nanoparticle components. Microfluidic 3D-channel arrangements enable symmetry-breaking and the spatial patterning of droplet hierarchies. This approach can produce internal gradients and hemispherically patterned, multilayered shells alongside chemical compartmentalization. Such organization enables incorporation of organic and inorganic components, including lipid bilayers, within the same entity. In this way, functional polarization, that imparts individual and collective directionality on the resulting artificial cells, is demonstrated. This approach enables exploitation of polarity and asymmetry, in conjunction with compartmentalized and networked chemistry, in single and higher-order organized structures, thereby increasing the palette of functionality in artificial cellular materials.

Dissolving microneedle based transdermal delivery of therapeutic peptide analogues.

Microneedle technology offers a viable means of delivering biologically active pharmaceutical agents across the skin in a minimally invasive and virtually pain free manner. Previous work detailed the first successful transdermal delivery of a model peptide drug, polymyxin b, utilising a dissolving polymer-based microneedle system. The focus of this study was to examine the ability of a dissolving microneedle system to deliver a range of peptides of different sizes and properties. Analogue versions of 2 existing therapeutic peptides; pentagastrin and sincalide, were synthesised utilising Fmoc based solid phase peptide synthesis (SPPS) chemistry techniques and once successfully synthesised and purified, the peptide analogues were characterised using LC-MS. The peptide analogues were then incorporated into PVP/trehalose microneedle formulations. Skin permeation testing, in addition to skin penetration testing, was carried out to determine the effectiveness of the microneedle system to deliver the peptide analogues through porcine skin. The results obtained from these studies were then compared with the permeation results obtained utilising polymyxin B as the peptide drug cargo to evaluate the PVP/trehalose microneedle system's suitability to successfully deliver therapeutic peptides. Results indicated that the microneedle system successfully systemically delivered a higher overall percentage of the encapsulated peptides at an initially faster rate than peptide loaded control discs and in therapeutically relevant concentrations.

Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients.

PURPOSE: Obesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer. METHODS: Hormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients. RESULTS: Univariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67-28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = - 0.75 and - 0.76, respectively, p = 0.02 for both). CONCLUSIONS: Higher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.

Social Relationships, Inflammation, and Cancer Survival.

Background: Social stressors, such as social relationship deficits, have been increasingly linked to chronic disease outcomes, including cancer. However, critical gaps exist in our understanding of the nature and strength of such links, as well as the underlying biological mechanisms relating social relationships to cancer progression and survival.Methods: Utilizing novel questionnaire and biomarker data from the UNC Health Registry/Cancer Survivorship Cohort, this study examines the associations between diverse measures of social support and mortality risk among individuals with cancer (N = 1,004). We further assess the role of multiple serum markers of inflammation, including high-sensitivity C-reactive protein (CRP), IL6, TNFα, and VEGF, as potential mediators in the social relationship-cancer link.Results: The findings revealed that one's appraisal of their social support was associated with cancer mortality, such that individuals reporting higher levels of social support satisfaction had lower mortality risk than individuals reporting lower levels of satisfaction. The amount of support received, on the other hand, was not predictive of cancer survival. We further found evidence that inflammatory processes may undergird the link between social support satisfaction and mortality among individuals with cancer, with individuals reporting higher levels of social support satisfaction having lower levels of CRP, IL6, and TNFα.Conclusions: These results provide new knowledge of the biosocial processes producing population disparities in cancer outcomes.Impact: Our study offers new insights for intervention efforts aimed at promoting social connectedness as a means for improving cancer survival. Cancer Epidemiol Biomarkers Prev; 27(5); 541-9. ©2018 AACR.

A sixteen-week three-armed, randomized, controlled trial investigating clinical and biochemical effects of targeted alterations in dietary linoleic acid and n-3 EPA+DHA in adults with episodic migraine: Study protocol.

Migraine is a prevalent neurological disorder, affecting over 16% of adult women and 7% of adult men in the U.S., causing significant pain, disability, and medical expense, with incomplete benefits from conventional medical management. Migraine, as a chronic pain syndrome, provides a practical model for investigating the impact of dietary modifications in omega-3 (n-3) and omega-6 (n-6) fatty acids. This paper reports the protocol of a trial to assess whether targeted dietary modifications designed to increase n-3 eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), with or without concurrent reduction in n-6 linoleic acid (LA), will alter nociceptive lipid mediators and mediate decreases in frequency and severity of migraine. This prospective, randomized, controlled trial in 153 male and female adult subjects, ages 18-99, with diagnosed and actively managed episodic migraine tests the efficacy, safety, and biochemical effects of targeted, controlled alterations in dietary omega-3 and omega-6 fatty acids. Participants are masked to diet hypotheses and all assessors are masked to treatment assignment. Following a four-week baseline period, participants with migraine headache frequency of 5-20 per month are randomized to one of three intensive dietary regimens for 16 additional weeks followed by a less intensive observation period. Dietary intervention arms include: 1) increased n-3 EPA+DHA with low n-6 linoleic acid (H3 L6); 2) increased n-3 EPA+DHA with usual US dietary intake of n-6 linoleic acid (H3 H6); and 3) usual US dietary content of n-3 and n-6 fatty acids (L3 H6). During the actual intervention, subjects receive content-specific study oils and foods sufficient for two meals and two snacks per day, as well as dietary counseling. Biochemical and clinical outcome measures are performed at intervals throughout this period. This randomized controlled trial is designed to determine whether targeted alterations in dietary n-3 and n-6 fatty acids can alter nociceptive lipid mediators in a manner that decreases headache pain and enhances quality of life and function in adults with frequent migraines. TRIAL REGISTRATION: NCT02012790.

Microfluidic Encapsulation Supports Stem Cell Viability, Proliferation, and Neuronal Differentiation.

Stem cell encapsulation technology demonstrates much promise for the replacement of damaged tissue in several diseases, including spinal cord injury (SCI). The use of biocompatible microcapsules permits the control of stem cell fate in situ to facilitate the replacement of damaged/lost tissue. In this work, a novel customized microfluidic device was developed for the reproducible encapsulation of neural stem cells (NSCs) and dental pulp stem cells (DPSCs) within monodisperse, alginate-collagen microcapsules. Both cell types survived within the microcapsules for up to 21 days in culture. Stem cells demonstrated retention of their multipotency and neuronal differentiation properties upon selective release from the microcapsules, as demonstrated by high proliferation rates and the production of stem cell and neuronal lineage markers. When cell-laden microcapsules were transplanted into an organotypic SCI model, the microcapsules effectively retained the transplanted stem cells at the site of implantation. Implanted cells survived over a 10 day period in culture after transplantation and demonstrated commitment to a neural lineage. Our device provides a quick, effective, and aseptic method for the encapsulation of two different stem cell types (DPSCs and NSCs) within alginate-collagen microcapsules. Since stem cells were able to retain their viability and neural differentiation capacity within such microcapsules, this method provides a useful technique to study stem cell behavior within three-dimensional environments.

Continuous and scalable polymer capsule processing for inertial fusion energy target shell fabrication using droplet microfluidics.

High specification, polymer capsules, to produce inertial fusion energy targets, were continuously fabricated using surfactant-free, inertial centralisation, and ultrafast polymerisation, in a scalable flow reactor. Laser-driven, inertial confinement fusion depends upon the interaction of high-energy lasers and hydrogen isotopes, contained within small, spherical and concentric target shells, causing a nuclear fusion reaction at ~150 M°C. Potentially, targets will be consumed at ~1 M per day per reactor, demanding a 5000x unit cost reduction to ~$0.20, and is a critical, key challenge. Experimentally, double emulsions were used as templates for capsule-shells, and were formed at 20 Hz, on a fluidic chip. Droplets were centralised in a dynamic flow, and their shapes both evaluated, and mathematically modeled, before subsequent shell solidification. The shells were photo-cured individually, on-the-fly, with precisely-actuated, millisecond-length (70 ms), uniform-intensity UV pulses, delivered through eight, radially orchestrated light-pipes. The near 100% yield rate of uniform shells had a minimum 99.0% concentricity and sphericity, and the solidification processing period was significantly reduced, over conventional batch methods. The data suggest the new possibility of a continuous, on-the-fly, IFE target fabrication process, employing sequential processing operations within a continuous enclosed duct system, which may include cryogenic fuel-filling, and shell curing, to produce ready-to-use IFE targets.

Bilayer Networks within a Hydrogel Shell: A Robust Chassis for Artificial Cells and a Platform for Membrane Studies.

The ability to make artificial lipid bilayers compatible with a wide range of environments, and with sufficient structural rigidity for manual handling, would open up a wealth of opportunities for their more routine use in real-world applications. Although droplet interface bilayers (DIBs) have been demonstrated in a host of laboratory applications, from chemical logic to biosynthesis reaction vessels, their wider use is hampered by a lack of mechanical stability and the largely manual methods employed in their production. Multiphase microfluidics has enabled us to construct hierarchical triple emulsions with a semipermeable shell, in order to form robust, bilayer-bound, droplet networks capable of communication with their external surroundings. These constructs are stable in air, water, and oil environments and overcome a critical obstacle of achieving structural rigidity without compromising environmental interaction. This paves the way for practical application of artificial membranes or droplet networks in diverse areas such as medical applications, drug testing, biophysical studies and their use as synthetic cells.

Evaluation of geometrical effects of microneedles on skin penetration by CT scan and finite element analysis.

Computerized tomography scan (CT scan) imaging and finite element analysis were employed to investigate how the geometric composition of microneedles affects their mechanical strength and penetration characteristics. Simulations of microneedle arrays, comprising triangular, square and hexagonal microneedle base, revealed a linear dependence of the mechanical strength to the number of vertices in the polygon base. A laser-enabled, micromoulding technique was then used to fabricate 3×3 microneedle arrays, each individual microneedle having triangular, square or hexagonal base geometries. Their penetration characteristics into ex-vivo porcine skin, were investigated for the first time by CT scan imaging. This revealed greater penetration depths for the triangular and square-based microneedles, demonstrating CT scan as a powerful and reliable technique for studying microneedle skin penetration.

Simple and Versatile 3D Printed Microfluidics Using Fused Filament Fabrication.

The uptake of microfluidics by the wider scientific community has been limited by the fabrication barrier created by the skills and equipment required for the production of traditional microfluidic devices. Here we present simple 3D printed microfluidic devices using an inexpensive and readily accessible printer with commercially available printer materials. We demonstrate that previously reported limitations of transparency and fidelity have been overcome, whilst devices capable of operating at pressures in excess of 2000 kPa illustrate that leakage issues have also been resolved. The utility of the 3D printed microfluidic devices is illustrated by encapsulating dental pulp stem cells within alginate droplets; cell viability assays show the vast majority of cells remain live, and device transparency is sufficient for single cell imaging. The accessibility of these devices is further enhanced through fabrication of integrated ports and by the introduction of a Lego®-like modular system facilitating rapid prototyping whilst offering the potential for novices to build microfluidic systems from a database of microfluidic components.

Roles of chemokines CCL2 and CCL5 in the pharmacokinetics of PEGylated liposomal doxorubicin in vivo and in patients with recurrent epithelial ovarian cancer.

Nanoparticles (NPs) are cleared by monocytes and macrophages. Chemokines CCL2 and CCL5 are key mediators for recruitment of these immune cells into tumors and tissues. The purpose of this study was to investigate effects of CCL2 and CCL5 on the pharmacokinetics (PKs) of NPs. Mice deficient in CCL2 or CCL5 demonstrated altered clearance and tissue distribution of polyethylene glycol tagged liposomal doxorubicin (PLD) compared to control mice. The PK studies using mice bearing SKOV3 ovarian cancer xenografts revealed that the presence of tumor cells and higher expression of chemokines were significantly associated with greater clearance of PLD compared to non-tumor bearing mice. Plasma exposure of encapsulated liposomal doxorubicin positively correlated with the total exposure of plasma CCL2 and CCL5 in patients with recurrent epithelial ovarian cancer treated with PLD. These data emphasize that the interplay between PLD and chemokines may have an important role in optimizing PLD therapy. FROM THE CLINICAL EDITOR: The use of nanoparticles as drug delivery carriers is gaining widespread acceptance in the clinical setting. However, the underlying pharmacokinetics of these novel drugs has not really been elucidated. In this interesting article, the authors carried out experiments using mice deficient in CCL2 or CCL5 to study the clearance of liposomal system. They showed the important role the immune system played and would enable better designs of future drug delivery systems.

Structural characterisation and transdermal delivery studies on sugar microneedles: experimental and finite element modelling analyses.

Dissolving microneedles are especially attractive for transdermal drug delivery as they are associated with improved patient compliance and safety. Furthermore, microneedles made of sugars offer the added benefit of biomolecule stabilisation making them ideal candidates for delivering biological agents such as proteins, peptides and nucleic acids. In this study, we performed experimental and finite element analyses to study the mechanical properties of sugar microneedles and evaluate the effect of sugar composition on microneedle ability to penetrate and deliver drug to the skin. Results showed that microneedles made of carboxymethylcellulose/maltose are superior to those made of carboxymethylcellulose/trehalose and carboxymethylcellulose/sucrose in terms of mechanical strength and the ability to deliver drug. Buckling was predicted to be the main mode of microneedle failure and the order of buckling was positively correlated to the Young's modulus values of the sugar constituents of each microneedle.

Clinical and subclinical effects of power brushing following experimental induction of biofilm overgrowth in subjects representing a spectrum of periodontal disease.

AIM: Investigate short-term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states. MATERIALS AND METHODS: Overall, 175 subjects representing each of five biofilm-gingival interface (BGI) periodontal groups were enrolled in a single-blind, randomized study. After stent-induced biofilm overgrowth for 21 days subjects received either a manual or a power toothbrush to use during a 4 weeks resolution phase. At baseline and during induction and resolution, standard clinical parameters were measured. Subclinical parameters included multikine analysis of 13 salivary biomarkers and 16s Human Oral Microbe Identification Microarray (HOMIM) probe analysis of subgingival plaque samples. RESULTS: All groups exhibited significantly greater reductions in bleeding on probing (BOP) (p = 0.002), gingival index (GI) (p = 0.0007), pocket depth (PD) (p = 0.04) and plaque index (p = 0.001) with power brushing compared to manual. When BGI groups were combined to form a shallow PD (PD ≤ 3 mm) and a deep PD group (PD > 4 mm) power brushing reduced BOP and GI in subjects with both pocket depths. Power brushing significantly reduced IL-1ß levels at resolution while changes in bacterial levels showed non-significant trends between both brushing modalities. CONCLUSIONS: Short-term changes in select clinical parameters and subclinical salivary biomarkers may be useful in assessing efficacy of power brushing interventions in a spectrum of periodontal disease states.