Polymeric Nanocapsules Containing Ozonated Oil and Terbinafine Hydrochloride as a Potential Treatment Against Dermatophytes.

Terbinafine hydrochloride is a synthetic allylamine whose mechanism of action consists of inhibiting the enzyme squalene epoxidase that participates in the first stage of ergosterol synthesis, interfering with fungal membrane function. Ozonated oils are used for topical application of ozone, producing reactive oxygen species that cause cellular damage in microorganisms, therefore being an alternative treatment for acute and chronic skin infections. This study aimed to develop and characterize Eudragit® RS100 nanocapsules, obtained by interfacial deposition of preformed polymer method, containing 0.5% terbinafine hydrochloride and 5% ozonated sunflower seed oil as a potential treatment against dermatophytes. The polymeric nanocapsules were characterized regarding particle size, zeta potential, pH, drug content, encapsulation efficiency, and stability. The in vitro drug release, in vitro skin permeation, and in vitro antifungal activity were also evaluated. The particle size was around 150 nm with a narrow size distribution, the zeta potential was around + 6 mV, and the pH was 2.2. The drug content was close to 95% with an encapsulation efficiency of 53%. The nanocapsules were capable to control the drug release and the skin permeation. The in vitro susceptibility test showed greater antifungal activity for the developed nanocapsules, against all dermatophyte strains tested, compared to the drug solution. Therefore, the polymeric nanocapsules suspension containing terbinafine hydrochloride and ozonated oil can be considered a potential high-efficacy candidate for the treatment of dermatophytosis, with a possible reduction in the drug dose and frequency of applications. Studies to evaluate safety and efficacy in vivo still need to be performed.

The use of electronic tongue and sensory panel on taste evaluation of pediatric medicines: a systematic review.

The palatability of medications is an essential factor for children's adherence to drug treatment. Several methods for drug taste assessment have been developed. The aim of this review is to explore the literature reports of the main methods for the evaluation of medicines taste, named electronic tongue (e-tongue, in vitro) and human sensory panel. A systematic search was performed up to March 2020 and a total of 88 articles were selected. The e-tongue (57.5%) has been more frequently described than the sensory panel (10.3%), while some articles (32.2%) used both techniques. 74.7% of the articles mentioned 'pediatric', 'paediatric' or 'children' in the text, but only 19.5% developed formulations targeting pediatric audience and sensory testing in children is rarely seen. The e-tongue has predominance of use in the taste evaluation of pediatric medicines probably since it is fast, easy to perform and risk free, besides presenting less imprecise data and no fatigue. The human panel is more realistic, despite its intrinsic variability. In this sense, it is proposed the use of e-tongue as a fast way to select the most promising sample(s) and, after that, the sensory panel should be applied in order to confirm the taste masking.

Omeprazole nanoparticles suspension: Development of a stable liquid formulation with a view to pediatric administration.

Omeprazole (OME) is often used to treat disorders associated with gastric hypersecretion in children but a liquid pediatric formulation of this medicine is not currently available. The aim of this study is to develop OME loaded nanoparticles with a view to the obtention of a liquid pharmaceutical dosage form. Eudragit® RS100 was selected as the skeleton material in the inner core and pH-sensitive Eudragit® L100-55 was used as the outer coating of the nanoparticles prepared by the nanoprecipitation method. Pharmacological activity was evaluated by induction of ethanol ulcers in mice. The OME nanoparticles exhibited mean diameters of 174 nm (±17), polydispersity index of 0.229 (±0.01), zeta potential values of -13 mV (±2.60) and encapsulation efficiency of 68.1%. The in vivo pharmacological assessment showed the ability of nanoparticles to protect mice stomach against ulcer formation. The prepared suspension of OME nanoparticles represents effective therapeutic strategy in a liquid pharmaceutical form with the possibility of pediatric administration.

Improved sensory properties of a nanostructured ritonavir suspension with a pediatric administration perspective.

The pediatric adherence to antiretroviral therapy is critical to therapeutic success. Ritonavir, a protease inhibitor drug, is commercially available as an oral solution containing a high amount of ethanol and propylene glycol, contraindicated in children younger than 4 years. Moreover, this medicine presents a bitter taste, which is limiting for the adherence to treatment. This study aims to develop ritonavir nanoparticles followed by polymeric coating for sensory characteristics improvement. The nanoparticles were coated with Eudragit® L 100-55 and characterized. A human sensory panel evaluated the proposed formulations regarding its bitter taste. The formulation showed nanotechnological features, with 130 and 134 nm for ritonavir nanoparticles and ritonavir coated nanoparticles, respectively. The pH, zeta potential, drug content and encapsulation efficiency results were suitable for oral administration. The coated nanoparticles were capable of decreasing the drug bitter taste as shown in the sensory analysis. The ritonavir incorporation in nanoparticles, followed by polymer coating can be a reasonable strategy to obtain alcohol free taste-masked medicines, which are promising for pediatric therapy.

Polymer-based wafers containing in situ synthesized gold nanoparticles as a potential wound-dressing material.

Polymer-based wafers containing gold nanoparticles (AuNP) were prepared using κ-carrageenan (κC), locust bean gum (LBG) and polyvinyl alcohol (PVA) at ratios of 42/22/13% w/w and 35/15/17% w/w. The synthesized AuNPs were evaluated for their particle size and morphology. The produced wafers containing AuNPs were investigated for their physicochemical, morphological, mechanical, and swelling properties. In addition, bacterial barrier activity and in vitro cytotoxicity were also evaluated in this study. The AuNPs obtained were spherical in shape (~ 10-15 nm in diameter) and exhibited a single bell-shaped UV-vis absorption band centered ~ 540 nm. FT-IR spectra of the wafers containing AuNPs exhibited a shift of ν(O=S=O) absorption band toward a lower wavenumber and a shift of ν(OH) absorption band toward a higher wavenumber due to the coordination of OH groups to AuNPs and their interaction with O=S=O groups of κC, respectively. SEM images confirmed the porous structure of the produced wafers, being the surface area, mechanical properties, and swelling behavior directly affected by changing both the initial amount of [Au+3] and the composition of the wafers. Lastly, the produced wafers showed non-toxicity to NIH-3T3 fibroblast cells, and they also serve as a bacterial barrier. These findings endorsed the claim that the produced wafers containing AuNPs could be a promising material for wound dressing applications.

One-pot synthesis of gold nanoparticles embedded in polysaccharide-based hydrogel: Physical-chemical characterization and feasibility for large-scale production.

In this study, polysaccharide-based hydrogel wound dressings containing in situ synthesized gold nanoparticles (AuNPs) were prepared by using a simple, fast and green protocol. The prepared hydrogels were characterized with UV-vis and infrared spectroscopy (FT-IR), and dynamic light scattering (DLS). The rheological and swelling properties and the feasibility to scale-up the wound dressing production from the lamination of the prepared hydrogel on non-woven fabric were also investigated. UV-vis spectra confirmed the AuNPs synthesis and the DLS results exhibited an increase in the size of AuNPs with increasing the initial Au3+ concentration. The rheological analysis showed that the augmentation of the initial Au3+ concentration reduces the gel viscosity and gelling temperature. Besides, the FT-IR spectra revealed that the AuNPs hinder the intermolecular interactions between kappa-carrageenan (κCG) and locust bean gum (LBG). The feasibility of scale-up the wound dressing production from the prepared hydrogel was confirmed through the lamination tests.

Smart wound dressing based on κ-carrageenan/locust bean gum/cranberry extract for monitoring bacterial infections.

A smart wound dressing based on carrageenan (κC), locust bean gum (LBG), and cranberry extract (CB) for monitoring bacterial wound infections was developed and characterized using UV-vis spectroscopy, FT-IR, and SEM. The mechanical, swelling, cytotoxic and pH sensor properties were also investigated. UV-vis spectra demonstrated that the obtained κC:LBG:CB hydrogel film exhibited a visible change of colors as it was immersed in PBS solution pH 5.0, 7.3 and 9.0. The spectra of FT-IR suggested that chemical interactions had occurred between κC and CB extract. The obtained κC:LBG:CB hydrogel film exhibited adequate mechanical properties and a swelling behavior dependent on pH. Cytotoxicity tests indicated that κC:LBG:CB hydrogel film had dose-dependent cytotoxicity against NIH 3T3 fibroblast cells. The in vitro studies using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated that the color changes of the κC:LBG:CB hydrogel film could be observed by naked eyes, confirming the potential use of the obtained hydrogel film as a visual system for monitoring bacterial wound infections.

Facile, green and scalable method to produce carrageenan-based hydrogel containing in situ synthesized AgNPs for application as wound dressing.

This manuscript was focused on introducing a facile, green and scalable method to produce kappa-carrageenan (κC) hydrogel membranes containing in situ synthesized silver nanoparticles (AgNPs). In a typical protocol, κC hydrogels were obtained by heating (sol phase), followed by cooling (gel phase) the polysaccharide solution, which enabled the simultaneous synthesis of AgNPs during the heating time. The as synthesized AgNPs were characterized spectrophotometrically, and by dynamic light scattering and transmission electron microscopy. The swelling properties at different pH and the antimicrobial activity of κC-AgNP hydrogel were investigated. AgNPs were mostly spherical in shape, crystalline in nature and measuring ca. 27nm in diameter. The in situ synthesis of AgNPs changed the swelling properties of κC hydrogel and also reduces its viscosity and gelling temperature. The AgNPs were continuously released from κC hydrogel for up to 48h in a concentration sufficient to prevent the bacterial growth as confirmed by antimicrobial tests. The simplicity involved in the AgNPs synthesis combined to the good spreadability of κC hydrogel makes this method suitable for scale-up to manufacturing quantities of wound dressing.

Characterization of membranes based on cellulose acetate butyrate/poly(caprolactone)triol/doxycycline and their potential for guided bone regeneration application.

This paper discusses the feasibility of using membranes based on cellulose acetate butyrate/poly(caprolactone)triol loaded with doxycycline for guided bone regeneration. Those membranes were obtained by solvent casting varying the cellulose acetate butyrate: poly(caprolactone)triol:doxycycline (CAB:PCL-T:DOX) mass ratios and characterized by scanning electron microscopy, differential scanning calorimetry, dynamical mechanical analysis, swelling and weight loss, drug release, in vitro antimicrobial activity and in vivo inflammatory response. Neat CAB and CAB:PCL-T:DOX membranes exhibited inner porous structure, which has a pore-size reduced with increasing of the PCL-T ratio. DSC results demonstrated that the molecular dispersion of the DOX into the CAB:PCL-T membrane was conditioned by PCL-T amount. Elastic modulus reduced noticeably with increased of the PCL-T ratio in the membrane from 2 to 3, while the strain at failure showed an increase of ca. 10-fold on the same condition. The DOX release mechanism from the membranes was found to be Fickian or quasi-Fickian diffusion. Membranes assessed immediately after the preparation, and even as the membranes immersed in synthetic saliva during 7 days, demonstrated significant inhibition in the growth of Staphylococcus aureus and Escherichia coli. Subcutaneous implant test on rat in vivo showed that the CAB:PCL-T:DOX membrane (7:3:1) did not trigger chronic inflammatory responses. These results suggest the feasibility in applying the CAB:PCL-T:DOX membrane as a barrier for guided bone regeneration.