Encapsulation of Photothermal Nanoparticles in Stealth and pH-Responsive Micelles for Eradication of Infectious Biofilms In Vitro and In Vivo

Photothermal nanoparticles can be used for non-antibiotic-based eradication of infectious biofilms, but this may cause collateral damage to tissue surrounding an infection site. In order to prevent collateral tissue damage, we encapsulated photothermal polydopamine-nanoparticles (PDA-NPs) in mixed shell polymeric micelles, composed of stealth polyethylene glycol (PEG) and pH-sensitive poly(β-amino ester) (PAE). To achieve encapsulation, PDA-NPs were made hydrophobic by electrostatic binding of indocyanine green (ICG). Coupling of ICG enhanced the photothermal conversion efficacy of PDA-NPs from 33% to 47%. Photothermal conversion was not affected by micellar encapsulation. No cytotoxicity or hemolytic effects of PEG-PAE encapsulated PDA-ICG-NPs were observed. PEG-PAE encapsulated PDA-ICG-NPs showed good penetration and accumulation in a Staphylococcus aureus biofilm. Penetration and accumulation were absent when nanoparticles were encapsulated in PEG-micelles without a pH-responsive moiety. PDA-ICG-NPs encapsulated in PEG-PAE-micelles found their way through the blood circulation to a sub-cutaneous infection site after tail-vein injection in mice, yielding faster eradication of infections upon near-infrared (NIR) irradiation than could be achieved after encapsulation in PEG-micelles. Moreover, staphylococcal counts in surrounding tissue were reduced facilitating faster wound healing. Thus, the combined effect of targeting and localized NIR irradiation prevented collateral tissue damage while eradicating an infectious biofilm.

Chitosan-Coated 5-Fluorouracil Incorporated Emulsions as Transdermal Drug Delivery Matrices

The purpose of the present study was to develop emulsions encapsulated by chitosan on the outer surface of a nano droplet containing 5-fluorouracil (5-FU) as a model drug. The emulsions were characterized in terms of size, pH and viscosity and were evaluated for their physicochemical properties such as drug release and skin permeation in vitro. The emulsions containing tween 80 (T80), sodium lauryl sulfate, span 20, and a combination of polyethylene glycol (PEG) and T20 exhibited a release of 88%, 86%, 90% and 92%, respectively. Chitosan-modified emulsions considerably controlled the release of 5-FU compared to a 5-FU solution (p < 0.05). All the formulations enabled transportation of 5-FU through a rat’s skin. The combination (T80, PEG) formulation showed a good penetration profile. Different surfactants showed variable degrees of skin drug retention. The ATR-FTIR spectrograms revealed that the emulsions mainly affected the fluidization of lipids and proteins of the stratum corneum (SC) that lead to enhanced drug permeation and retention across the skin. The present study concludes that the emulsions containing a combination of surfactants (Tween) and a co-surfactant (PEG) exhibited the best penetration profile, prevented the premature release of drugs from the nano droplet, enhanced the permeation and the retention of the drug across the skin and had great potential for transdermal drug delivery. Therefore, chitosan-coated 5-FU emulsions represent an excellent possibility to deliver a model drug as a transdermal delivery system.

Alkylimidazolium Ionic Liquids Absorption and Diffusion in Wood

Ionic liquids represent a class of highly tunable organic compounds responsible for many applications in the domain of wood-based materials. It has often been emphasized that the use of ionic liquids derives from their high affinity for lignocellulose and their good penetration ability into wood structures. This paper discusses the sorption ability of different types of 1-alkyl-3-methylimidazolium ionic liquids with lateral alkyl chains, ranging from ethyl to hexyl into spruce and beech wood, as a function of their cation molecular mass, anion type (chloride, tetrafluoroborate, acetate), and intrinsic properties (surface tension and kinematic viscosity) at room temperature. All the studied ionic liquids present high relative uptake values at the equilibrium, ranging from 11.2% to 69.7%. The bulk diffusion coefficients of the ionic liquids into the wood range from 2 × 10−3 to 28 × 10−3 mm2/min, being higher in the longitudinal direction for both types of wood. The value of the diffusion coefficients for 1-ethyl-3-methylimidazolium chloride is only 25% lower than that for water, despite the obvious differences in viscosity and surface tension, demonstrating a good penetration ability and the potential for wood industry-related applications (as impregnation compound carriers and preservatives).

Synthesis and self-assembly of curcumin-modified amphiphilic polymeric micelles with antibacterial activity

Background The ubiquitous nature of bacterial biofilms combined with the enhanced resistance towards antimicrobials has led to the development of an increasing number of strategies for biofilm eradication. Such strategies must take into account the existence of extracellular polymeric substances, which obstruct the diffusion of antibiofilm agents and assists in the maintenance of a well-defended microbial community. Within this context, nanoparticles have been studied for their drug delivery efficacy and easily customised surface. Nevertheless, there usually is a requirement for nanocarriers to be used in association with an antimicrobial agent; the intrinsically antimicrobial nanoparticles are most often made of metals or metal oxides, which is not ideal from ecological and biomedical perspectives. Based on this, the use of polymeric micelles as nanocarriers is appealing as they can be easily prepared using biodegradable organic materials. Results In the present work, micelles comprised of poly(lactic-co-glycolic acid) and dextran are prepared and then functionalised with curcumin. The effect of the functionalisation in the micelle’s physical properties was elucidated, and the antibacterial and antibiofilm activities were assessed for the prepared polymeric nanoparticles against Pseudomonas spp. cells and biofilms. It was found that the nanoparticles have good penetration into the biofilms, which resulted in enhanced antibacterial activity of the conjugated micelles when compared to free curcumin. Furthermore, the curcumin-functionalised micelles were efficient at disrupting mature biofilms and demonstrated antibacterial activity towards biofilm-embedded cells. Conclusion Curcumin-functionalised poly(lactic-co-glycolic acid)-dextran micelles are novel nanostructures with an intrinsic antibacterial activity tested against two Pseudomonas spp. strains that have the potential to be further exploited to deliver a secondary bioactive molecule within its core. Graphic Abstract

SAR distribution of non-invasive hyperthermia with microstrip applicators on different breast cancer stages

<span>This paper presents the microstrip antenna with different applied frequencies used as a non-invasive hyperthermia applicator. This non-invasive hyperthermia applicator is introduced to clarify the sufficient heat distribution on the treated tissue for different breast cancer stages. 57 mammogram breast cancer images from early-stage to stage-3 are analyzed to obtain the required penetration depth and focus position distance. Then, the simulation-based experiment is carried out to observe the heating distribution on different stages of cancer with two different operating frequencies; 915MHz and 2450MHz. Also included in this paper is the prediction on the period for hyperthermia treatment planning execution. Based on the results, various penetration depths are obtained when different operating frequencies are applied. 915MHz antenna showed better results when compared to 2450MHz, where microstrip applicator with 915MHz is able to heat cancer at stage-1, stage-2, and stage-3 with good penetration depth and focus position distance, while 2450MHz only performed well in early-stage cancer. Meanwhile, different stages require various periods of time. From the results, the shortest period for hyperthermia execution simulated in the early-stage and then followed by stage-3, stage-2, and the longest period is in stage-1.</span>

Hypoxia-alleviated sonodynamic therapy based on a hybrid protein oxygen carrier to enhance tumor inhibition

Sonodynamic therapy (SDT) is a highly attractive therapy due to its advantages of being non-invasive and having good penetration depth, but tumor hypoxia extremely restricts its therapeutic effect.

Headaches and Magnesium: Mechanisms, Bioavailability, Therapeutic Efficacy and Potential Advantage of Magnesium Pidolate

Magnesium deficiency may occur for several reasons, such as inadequate intake or increased gastrointestinal or renal loss. A large body of literature suggests a relationship between magnesium deficiency and mild and moderate tension-type headaches and migraines. A number of double-blind randomized placebo-controlled trials have shown that magnesium is efficacious in relieving headaches and have led to the recommendation of oral magnesium for headache relief in several national and international guidelines. Among several magnesium salts available to treat magnesium deficiency, magnesium pidolate may have high bioavailability and good penetration at the intracellular level. Here, we discuss the cellular and molecular effects of magnesium deficiency in the brain and the clinical evidence supporting the use of magnesium for the treatment of headaches and migraines.

Formulation and Stability Testing of Microemulsion Griseovulfin

The use of drugs that are less soluble in water will become clinically less efficient, this is caused by the low penetration of the drug into the body. A microemulsion is a dispersion system such as an emulsion that can increase the solubility of drugs that are sometimes difficult to dissolve in water. Microemulsions have long-term stability, clear, transparent, and good penetration capabilities. In this study, a microemulsion formulation with active ingredients griseofulvin and virgin coconut oil was conducted as an oil phase. The resulting microemulsion evaluates physical stability during 35 storage days. The results showed that the microemulsion preparation remained stable during storage time without changes in color, odor, and consistency, while the pH and dosage viscosity experienced less significant changes. The consequences of the centrifugation test at 3700 rpm for 5 hours and freezing tests for 24 days showed stable preparation and cannot be separated. The diffusion test results obtained by FG2 had the largest permeation percentages of 3.6136%, FG3 2.8724%, and the smallest FG1 2.0477%.Keywords: microemulsion, griseofulvin, stability, diffusion test

The Variation Effect of Electric Current Toward Tensile Strength on Low Carbon Steel Welding with Electrode E7018

The strength of the welding result is strongly influenced by several factors, one of which is the selection of high current. This study aims to determine the effect of high current of welding on the strength of low carbon steel welding joints. The process of welding the material uses the open V seam connection type. The variations of the high current used were 80 A, 100 A and 130 A. The specimen used was a carbon steel plate with code of 1.0038 with thickness of 8 mm and the electrode used was the E7018 electrode with diameter of 3.2 mm. The strength of the welding results is influenced by arc voltage, amount of current, welding speed, amount of penetration and electric polarity. Determination of the amount of current in metal joints using arc welding affects the work efficiency and welding materials. Based on the research, it was found that welding using high current of 100 ampere produced the highest tensile strength value of all test specimens that were given welding treatment and good penetration results.

CLINICAL AND MICROBIOLOGICAL ASSESSMENT OF ROOT CANAL DECONTAMINATION IN CHRONIC APICAL PERIODONTITIS USING THE ULTRASOUND

The aim: To study the effectiveness of chronic apical periodontitis treatment by the combined use of ultrasonic treatment of root canals and multicomponent antimicrobial gel according to the results of clinical and microbiological researches. Materials and methods: 64 patients with chronic apical periodontitis at the age of 18-56 years were treated. Patients were divided into two groups: the main and control. In the main group the root canals of 36 teeth were sonicated in combination with multicomponent antimicrobial gel, in the control – 35 teeth were treated by a standard method. The content of the root canals for microbiological studies was obtained before endodontic treatment and before permanent obturation. Frequency of content and number of bacteria in the samples were evaluated. Results: All samples before treatment were positive for the presence of variable bacterial flora, among which Staphylococcus epidermidis (43.9%), Enterococcus faecalis (37.9%), Streptococcus spp. (24.8%), Candida albicans (24.4%), Fusibacterium (9.4%) were the most dominant, their number was 7.4-4.8 lg CFU/ml. Repeated research after the proposed and standard method of root canal decontamination has shown a significant decrease in microflora. According to the data of clinical and microbiological examination, the method which was developed by us revealed a positive result in 86% of cases compared with 63% when treated by the standard method. Conclusions: The effectiveness of a complex treatment method with combined use of the ultrasonic irrigation and multicomponent antimicrobial gel for root canals decontamination in chronic apical periodontitis is demonstrated. Significant reduction of microflora growth and destruction of microbial associations, good penetration of multicomponent antimicrobial gel into endodontic structures due to ultrasound compared with a standard method were achieved.