Preparation and characterization of indomethacin loaded films by piezoelectric inkjet printing: a personalized medication approach.

The purpose of this study was to investigate the application of piezoelectric inkjet technology in the preparation of custom-made indomethacin (IMC) films. Indomethacin solutions with and without PVP were printed onto polymeric sheets using a commercial inkjet printer. Drug loading was varied by selecting a machine parameter different dots per inches (DPIs). The printed patches were evaluated for particulate morphologies, drug loading, in vitro release and ex vivo skin permeation and anti-inflammatory effects using hind paw inflammation model. Calculated drug loaded in 2 × 2 cm2 patches of IMC of 96, 300, and 600 DPIs were in the range of 40, 60, and 65 µg, respectively. Patches loaded with IMC alcoholic solution showed crystalline structures observed by scanning electron microscopy and the addition of PVP in solution turned it to amorphous form. The drug release profile showed 60-70% of total drug released in 3 h. Permeation studies showed 40-50% of total drug loaded permeated through rat skin using Franz cells. Patches with higher printing density 600 DPI showed anti-inflammatory effect in hind paw inflammation model studies. This study has shown the potential of personalized medicine in which a calculated amount of drug can be delivered to patients by piezoelectric technology.

Transdermal Microneedles-A Materials Perspective.

Transdermal drug delivery is an emerging field in the pharmaceutical remit compared with conventional methods (oral and parenteral). Microneedle (MN)-based devices have gained significant interest as a strategy to overcome the skin's formidable barrier: the stratum corneum. This approach provides a less invasive, more efficient, patient friendly method of drug delivery with the ability to incorporate various therapeutic agents including macromolecules (proteins and peptides), anti-cancer agents and other hydrophilic and hydrophobic compounds. This short review attempts to assess the various materials involved in the fabrication of MNs as well as incorporation of other excipients to improve drug delivery for novel medical devices. The focus will be on polymers, metals and other inorganic materials utilised for MN drug delivery, as well as their application, limitations and future work to be carried out.

Engineering optimisation of commercial facemask formulations capable of improving skin moisturisation.

INTRODUCTION: The stratum corneum is the biggest obstacle in cosmetics with respect to skin moisturisation. Many approaches have been taken to overcome the barrier, one of which is incorporating natural cosmeceuticals into cosmetic products to enhance moisturisation effects. Here, a commercial facemask formulation was electrospun to develop dry facemasks capable of hosting cosmeceuticals within the pores of incorporated mesoporous silica. METHODS: Ethanolic solutions containing 40% w/w of the marketed facemask (7th Heaven Dead Sea peel-off facemask) and mesoporous silica were prepared and electrically processed at 30 µL min-1 at an applied voltage of 12 ± 2 kV. In vitro characterisation and release studies using fluorescein dye as a model probe were carried out. RESULTS: SEM images confirmed the fibrous nature of the resulting matrix; showing an average fiber diameter of 298.32 nm. The electrospun mask was found to be advantageous due to this fibrous nature providing high active loading capacity whilst demonstrating 100% probe release within 60 min. Contact Angle hysteresis, thermal analysis and Fourier Transform Infrared Spectroscopy (FTIR) presented evidence of compatibility and stability of and within the formulation. CONCLUSION: Adapting the formulation of a commercial polymeric facemask into an electrospun facemask has shown the versatility of the electrospinning process; now successfully crossing over into the cosmetic industry.

INTRODUCTION: La couche cornée est le premier obstacle à l'hydratation de la peau par des produits cosmétiques. De nombreuses approches ont été adoptées pour surmonter cette entrave, dont l'une consiste à intégrer des cosméceutiques naturels dans les produits cosmétiques afin d'augmenter leur pouvoir hydratant. Ici, la formulation commercialisée d'un masque pour le visage a été modifiée par électrofilage de manière à développer des masques secs pouvant intégrer des cosméceutiques dans les pores de silice mésoporeuse présent dans le produit. MÉTHODES: Des solutions éthanoliques, contenant 40 % p/p du masque pour le visage commercialisé (masque peel-off 7th Heaven Dead Sea) et de la silice mésoporeuse ont été préparées et traitées électriquement à 30 µl/min_ 1, avec une tension appliquée de 12 ± 2 kV. Des études de caractérisation et de libération in vitro ont été menées, utilisant un colorant fluorescéine en tant que sonde. RÉSULTATS: Des images SEM ont confirmé la nature fibreuse de la matrice résultante, avec un diamètre de fibre moyen s'élevant à 298,32 nm. Le masque électrofilé a été jugé avantageux en raison de sa nature fibreuse, qui permet une capacité de charge élevée, ainsi qu'une libération de 100 % de la sonde dans les 60 min. L'hystérèse de l'angle de contact, l'analyse thermique et la spectroscopie infrarouge à transformée de Fourier (IRTF) ont permis d'identifier des preuves de compatibilité et de stabilité dans cette formulation. CONCLUSION: La possibilité d'adapter la formulation d'un masque pour le visage polymérique déjà commercialisé pour en faire un masque électrofilé montre la polyvalence du processus d'électrofilage, qui fait une apparition remarquable dans le domaine des cosmétiques.

Porous Inorganic Drug Delivery Systems-a Review.

Innovative methods and materials have been developed to overcome limitations associated with current drug delivery systems. Significant developments have led to the use of a variety of materials (as excipients) such as inorganic and metallic structures, marking a transition from conventional polymers. Inorganic materials, especially those possessing significant porosity, are emerging as good candidates for the delivery of a range of drugs (antibiotics, anticancer and anti-inflammatories), providing several advantages in formulation and engineering (encapsulation of drug in amorphous form, controlled delivery and improved targeting). This review focuses on key selected developments in porous drug delivery systems. The review provides a short broad overview of porous polymeric materials for drug delivery before focusing on porous inorganic materials (e.g. Santa Barbara Amorphous (SBA) and Mobil Composition of Matter (MCM)) and their utilisation in drug dosage form development. Methods for their preparation and drug loading thereafter are detailed. Several examples of porous inorganic materials, drugs used and outcomes are discussed providing the reader with an understanding of advances in the field and realistic opportunities.

Polymeric Based Therapeutic Delivery Systems Prepared Using Electrohydrodynamic Processes.

The development of therapeutic dosage (e.g. pharmaceutical) systems is an ongoing process which, in recent times has incorporated several emerging disciplines and themes at timely intervals. While the concepts surrounding dosage forms have developed and evolved, many polymeric excipients remain as the preferred choice of materials over existing counterparts, serving functions as matrix materials, coatings and providing other specific functional properties (e.g. adhesion, controlled release and mechanical properties). There have been, however, developments in the deployment of synthetic polymeric materials (e.g. polycaprolactone, poly lactic co-glycolic acid) when compared to naturally occurring materials (e.g. lactose, gelatin). Advances in pharmaceutical process technologies have also provided novel engineering platforms to develop a host of exciting structure based materials ranging from the nanometer to the macro scales. Some of these structure enabling technologies include spray drying, super critical processing, microfluidics and even wet chemical methods. More recently electrohydrodynamic (EHDA) engineering methods have emerged as robust technologies offering potential to fabricate a plethora of generic structures (e.g. particles, fibres, bubbles and pre-determined patterns) on a broad scale range. This review focuses on key developments using various EHDA technologies for the pharmaceutical and biomaterial remits when selecting synthetic and/or naturally occurring polymers as pharmaceutical (and therapeutic) excipients. In addition, the underlying EHDA process principles are discussed along with key parameters and variables (both materials and engineering). EHDA technologies are operational at ambient conditions and recent developments have also demonstrated their viability for large scale production. These are promising technologies which have potential in established (e.g. films, dressings and microparticles) and emerging scientific themes (e.g. nanomedicines and tissue engineering).

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model.

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Targeting FK506 binding proteins to fight malarial and bacterial infections: current advances and future perspectives.

There is an urgent need for the design and development of new and selective drugs for the treatment of malaria and bacterial infections as these pathogens are developing resistance to presently available therapies. Malaria is a life threatening disease in many countries and responsible for almost one million deaths annually. In particular, drug-resistant malarial parasites are hindering effective control of malaria and prompting to find novel druggable targets and develop compounds with mechanism of action different from the conventional drugs. In this quest, efforts were made to determine three-dimensional structures of Plasmodium falciparum and Plasmodium vivax FK506 binding proteins which bind the macrolides (FK506 and rapamycin) and also demonstrate peptidylprolyl cis-trans isomerase activity in a similar manner as human FKBP12. Previous studies revealed that the immunosuppressive drug FK506 exhibits potential anti-malarial activity by binding FK506 binding domains (FKBD). This review focuses on three different types of FK506 binding proteins/domains in pathogens, their structural characteristics and biological roles. Binding ability of these proteins with the macrolides has opened new possibilities to develop selective inhibitors for these novel targets to combat the life threatening infections.

Increased expression of extracellular proteins as a hallmark of human endothelial cell in vitro senescence.

A convenient way to study processes of aging in distinct human tissues consists of a molecular analysis of cells from the tissue in question, that were explanted and grown in vitro until they reach senescence. Using human umbilical vein endothelial cells (HUVEC), we have established an in vitro senescence model for human endothelial cells. A major hallmark of HUVEC in vitro senescence is the increased frequency of apoptotic cell death, which occurs as a determining feature of HUVEC senescence. Senescent endothelial cells are also found in vivo in atherosclerotic lesions, suggesting that the presence of such cells may contribute to the development of vascular pathology. To elucidate mechanisms underlying endothelial cell senescence and age-associated apoptosis, gene expression analyses were carried out. In these experiments, we observed the up-regulation of genes coding for extracellular proteins in senescent HUVEC. In particular, a significant upregulation of interleukin-8, VEGI, and the IGF-binding proteins 3 and 5 was observed. Upregulation of these genes was confirmed by both RT-PCR and Western blot. In the case of interleukin-8, a roughly 50-fold upregulation of the protein was also found in cellular supernatants. The extracellular proteins encoded by these genes are well known for their ability to modulate the apoptotic response of human cells, and in the case of interleukin-8, clear links to the establishment of atherosclerotic lesions have been defined. The results described here support a new model, where changes in the secretome of human endothelial cells contribute to vascular aging and vascular pathology.

Cantharidin revisited: a blistering defense of an ancient medicine.

Cantharidin, a vesicant produced by beetles in the order Coleoptera, has a long history in both folk and traditional medicine. In dermatology, topical cantharidin has long been used to treat warts and molluscum. In 1962, cantharidin lost Food and Drug Administration (FDA) approval owing to the failure of its manufacturers to submit data attesting to cantharidin's efficacy. However, it is expected that the FDA will soon include cantharidin on its "Bulk Substances List," which would permit physicians or pharmacists to compound cantharidin to be used in the office for individual patients. A comprehensive discussion of the origins, folk uses, current FDA status, current dermatologic uses, and effects of cantharidin poisoning has been compiled herein. No cases of systemic intoxication or scarring have been reported with the proper use of cantharidin by a physician. Cantharidin is a safe and valuable medication and should be readded to the dermatologic therapeutic armamentarium.

Congenital self-healing reticulohistiocytosis with eye involvement.

Congenital self-healing reticulohistiocytosis (CSHR) represents the benign end of the spectrum of Langerhans cell histiocytoses, with spontaneous resolution of lesions within the first year of life. However, involvement of organ systems other than the skin has been described occasionally and recurrence of disease at sites distant from the skin has been documented. We report a case of CSHR with eye involvement that spontaneously resolved concurrent with resolution of skin lesions. Because multiple organ systems can be involved and recurrences are possible, long-term follow-up of these patients is indicated.

Trichorhinophalangeal syndrome, type II (Langer-Giedion syndrome).

Trichorhinophalangeal syndrome (TRPS) is characterized by its unique facial features and skeletal abnormalities. A bulbous, pear-shaped nose, elongated philtrum, sparse hair, cone-shaped epiphyses and mild growth retardation are found in both type I (TRPSI) and type II (TRPSII). TRPSII can be distinguished from TRPSI when multiple exostoses or redundant skin are present. While TRPSI is inherited in an autosomal dominant fashion, most cases of TRPSII are sporadic although there are a few cases which are familial. The following is a case report of TRPSII with incomplete penetrance in the index case and exostoses and growth retardation in the patient's two siblings.

Topical tretinoin and 5-fluorouracil in the treatment of linear verrucous epidermal nevus.

Treatment of a linear verrucous epidermal nevus using topical 0.1% tretinoin cream and 5% 5-fluorouracil in a young patient is described. In 1994, successful topical therapy using this combination was described in the management of an inflammatory linear verrucous epidermal nevus. We report another case in which treatment of a noninflamed epidermal verrucous nevus with 0.1% tretinoin and 5% 5-fluorouracil resulted in significant improvement. An updated summary of the literature discussing management of epidermal nevi is presented.

Advances in the management of dysphagia caused by stroke.

This article reviews the advancements that have occurred, primarily in the last decade, in the management and treatment of swallowing disorders related to stroke. An overview of swallowing physiology is given, and interventions, both indirect and direct, are explored. Expanding knowledge, applying techniques from other scientific disciplines, and developing new technologies provide hope for stroke patients who experience dysphagia.

Update on juvenile xanthogranuloma: unusual cutaneous and systemic variants.

Juvenile xanthogranuloma (JXG) is a well-recognized benign disorder of infancy and early childhood characterized by yellowish cutaneous nodules that spontaneously regress over months to years. In the vast majority of children, JXG is limited to the skin and requires no treatment. Over the past two decades, unusual cutaneous and systemic forms of JXG have been increasingly reported. JXGs have been discovered, usually unexpectedly, in every organ system of the body. Correct diagnosis is crucial to prevent unnecessary invasive diagnostic and therapeutic procedures. Unusual clinical and histological variants of JXG often require immunohistochemical studies and/or electron microscopy to establish the diagnosis. Nonlipidized, giant, intramuscular, subcutaneous, and clustered JXG are but some of the variants that are discussed in this article. The immunohistochemistry of JXG, current nosology, and hypotheses regarding the origins of JXG are also reviewed.

Contour tracking using a knowledge-based snake algorithm to construct three-dimensional pharyngeal bolus movement.

Videofluorography (VFG) using a barium-mixed bolus is in wide clinical use for assessing patients with swallowing disorders. VFG is usually done with both lateral (LA) and anterior-posterior (AP) views, most commonly in two separate sittings. A real-time, three-dimensional (3-D) representation of the evolution of a pharyngeal bolus and its volumetric information can potentially help clinicians analyze and visualize the kinematics of swallowing, dysphagia, and compensatory therapeutic strategies. Active contour models, also known as "Snakes," have been used to solve various image analysis and computer vision problems. We applied a Snake algorithm to automate in part the contour tracking and reconstruction of VFG images to visualize and quantitatively analyze the 3-D evolution of a pharyngeal bolus. To improve the accuracy of the Snake search, we provided the additional "knowledge" of the pharyngeal image itself, which served as an extra constraint to push the Snake curve toward the desired contour. VFG of pharyngeal bolus transport in a normal subject was recorded by using barium-mixed boluses (viscosity: 185 centipoise, density: 2.84 g/cc) with volumes of 5, 10, and 20 ml. The resulting LA and AP video images were digitally captured and matched frame by frame. The knowledge-based Snake search algorithm was used to generate Snake points to satisfy both internal (i.e., smoothness) and external (i.e., boundary fitting) constraints. Using these Snake points, we traced the 3-D bolus movement at each time instant, assuming elliptic geometry in the cross-section of the pharyngeal bolus. By concentrating the 3-D images for each time instant, we developed a 3-D movie representing pharyngeal bolus movement. The efficiency, reproducibility, and accuracy of this algorithm in tracing pharyngeal bolus boundaries and estimating front/tail velocities were assessed and found satisfactory. We conclude that 3-D pharyngeal bolus movement can be traced both accurately and efficiently by using a knowledge-based Snake search algorithm.