Targeting Leishmania Promastigotes and Amastigotes Forms through Amino Acids and Peptides: A Promising Therapeutic Strategy.

Millions of people worldwide are affected by leishmaniasis, caused by the Leishmania parasite. Effective treatment is challenging due to the biological complexity of the parasite, drug toxicity, and increasing resistance to conventional drugs. To combat this disease, the development of specific strategies to target and selectively eliminate the parasite is crucial. This Review highlights the importance of amino acids in the developmental stages of Leishmania as a factor determining whether the infection progresses or is suppressed. It also explores the use of peptides as alternatives in parasite control and the development of novel targeted treatments. While these strategies show promise for more effective and targeted treatment, further studies to address the remaining challenges are imperative.

Fluorescent Techniques for RNA Detection in Nanoparticles.

The utilization of drug delivery systems, such as lipid nanoparticles and polyplexes/micelleplexes, has shown promise in intracellularly delivering nucleic acids for addressing various diseases. Accurate quantification of the nucleic acid cargo within nanoparticles is essential for the development of safe and effective nanomedicines. Currently, the RiboGreen and SYBR Gold methods are regarded as standard techniques for the precise quantification of RNA in lipid nanoparticles and polyplexes/micelleplexes, respectively. In this chapter, we present a comprehensive protocol for the precise evaluation of the encapsulation efficiency in such formulations using these methods. Additionally, we offer detailed instructions for nanoparticle preparation, characterization, and a comparative analysis of the sensitivity of both methods in quantifying unencapsulated siRNA.

Antifungal Activity of Aniba canelilla (Kunth) Mez Essential Oil and Its Main Compound 1-Nitro-2-Phenylethane against Dermatophytes.

The essential oil of Aniba canelilla (Kunth) Mez (EOAC), an Amazon plant composed of a rare nitro compound, has shown scientific evidence of antifungal activity but is still unexplored against dermatophytes. The antifungal susceptibility of EOAC and its main compound, 1-nitro-2-phenylethane (NP), was evaluated against dermatophytes (Trichophyton rubrum, T. mentagrophytes and Microsporum canis), evidencing antifungal activity with an inhibitory concentration lower than 256 µg/mL. The mechanism of action was also evaluated, and it is suggested that EOAC and NP have fungicidal action in the fungal membrane, since the antifungal activity occurs through a modification of the shape of the conidial structures of the fungus, showing the permeability of the intracellular content due to the visually observed plasmolysis and cytosolic extravasation through an osmotic process. These results suggest the essential oil and its main compound are promising plant-derived alternatives for treating ungual dermatophytosis.

Poly(methylmethacrylate-co-dimethyl acrylamide)-silver nanocomposite prevents biofilm formation in medical devices.

Aim: To investigate whether medical devices coated with a synthesized nanocomposite of poly(methylmethacrylate-co-dimethyl acrylamide) (PMMDMA) and silver nanoparticles (AgNPs) could improve their antibiofilm and antimicrobial activities. We also investigated the nanocomposite's safety. Materials & methods: The nanocomposite was synthesized and characterized using analytical techniques. Medical devices coated with the nanocomposite were evaluated for bacterial adhesion and hemolytic activity in vitro. Results: The nanocomposite formation was demonstrated with the incorporation of AgNPs into the polymer matrix. The nanocomposite proved to be nonhemolytic and significantly inhibited bacterial biofilm formation. Conclusion: The PMMDMA-AgNPs nanocomposite was more effective in preventing biofilm formation than PMMDMA alone and is a promising strategy for coating medical devices and reducing mortality due to hospital-acquired infections.

Cosmetic application of the stem-bark extract of Bertholletia excelsa H.B.K.

OBJECTIVE: The Amazon has a rich biodiversity where many different plant species can be found. This diversity is an important source of bioactive substances, mainly due to the different structural components of their phytometabolites. Research for natural products is a strategy for the development of new agents in therapeutic applications, especially cosmetic applications, that have better pharmacological potential. Within this perspective, the objective of the study was to investigate the cosmetic application (anti-aging potential) of the stem-bark extract of Bertholletia excelsa H.B.K - (SBEBE), popularly known as the Brazil nut tree, here called SBEBE, a noble plant species of the Amazon that is rich in selenium. METHODS: Enzymatic, glycation, proliferation, cell-healing, collagen quantification, toxicity and genotoxicity assays were used. RESULTS: Among the enzymes involved in the extracellular matrix of the skin, SBEBE was able to inhibit only elastase (62.67 ± 3.75) when compared to the standard sivelestat (89.04 ± 0.53), and the extract was also able to inhibit both the oxidative and the non-oxidative pathway. When cell toxicity in fibroblasts (MRC-5) and keratinocytes (HACAT) was evaluated, SBEBE did not present toxicity in 24 h of incubation. After this period, the extract showed average cytotoxicity in 48 and 72 h, but not enough to reach the concentration of 50% of MRC-5 fibroblasts. In the trypan blue assay, the extract promoted fibroblast proliferation in 24, 48 and 72 h of incubation, which was evaluated through exponential cell growth, with emphasis mainly on the lowest concentration with results higher than the standard. When the cell healing capacity was evaluated, in 48 h of exposure to fibroblast, SBEBE was able to induce a cell carpet (cell film) in the cell monolayer scratch assay. CONCLUSIONS: SBEBE stimulated collagen production at all concentrations tested. In the alkaline comet assay, at the lowest concentration, the extract did not induce DNA damage when compared to the reference drug doxorubicin. This study proved that SBEBE extract can be considered an ally in the treatment of skin anti-ageing as a possible biotechnological, phytocosmetic product.

OBJECTIF: L'Amazonie possède une riche biodiversité ou l'on trouve de nombreuses espèces végétales différentes. Cette diversité constitue une source importante de substances bioactives, principalement en raison des différents composants structurels de leurs phytométabolites. La recherche de produits naturels est une stratégie de développement de nouveaux agents à applications thérapeutiques, notamment cosmétiques, présentant un meilleur potentiel pharmacologique. Dans cette perspective, l'objectif de l'étude était d'étudier l'application cosmétique (potentiel anti-âge) de l'extrait d'écorce de tige de Bertholletia excelsa H.B.K - (SBEBE), communément connu sous le nom de noix du Brésil, ici appelé SBEBE, un arbre noble, espèce végétale d'Amazonie riche en sélénium. MÉTHODES: Des tests enzymatiques, de glycation, de prolifération, de guérison cellulaire, de quantification du collagène, de toxicité et de génotoxicité ont été utilisés. RÉSULTATS: Parmi les enzymes impliquées dans la matrice extracellulaire de la peau, le SBEBE était capable d'inhiber uniquement l'élastase (62,67 +- 3,75) par rapport au sivelestat standard (89,04 +- 0,53), et l'extrait était également capable d'inhiber à la fois la voie oxydative et non-oxydative. Lorsque la toxicité cellulaire dans les fibroblastes (MRC-5) et les kératinocytes (HACAT) a été évaluée, SBEBE n'a présenté aucune toxicité en 24 heures d'incubation. Après cette période, l'extrait a montré une cytotoxicité moyenne en 48 et 72 h, mais pas suffisamment pour atteindre la concentration de 50 % de fibroblastes MRC-5. Dans le test au bleu trypan, l'extrait a favorisé la prolifération des fibroblastes en 24, 48 et 72 heures d'incubation, qui a été évaluée par une croissance cellulaire exponentielle, en mettant l'accent principalement sur la concentration la plus faible avec des résultats supérieurs à la norme. Lorsque la capacité de guérison cellulaire a été évaluée, en 48 heures d'exposition aux fibroblastes, SBEBE a pu induire un tapis cellulaire (film cellulaire) dans le test de grattage de la monocouche cellulaire. CONCLUSIONS: SBEBE a stimulé la production de collagène à toutes les concentrations testées. Dans le test alcalin des comètes, à la concentration la plus faible, l'extrait n'a pas induit de dommages à l'ADN par rapport au médicament de référence, la doxorubicine. Cette étude a prouvé que l'extrait de SBEBE peut être considéré comme un allié dans le traitement anti-âge cutané en tant que possible produit biotechnologique et phytocosmétique.

Targeted Molecular Therapeutics for Pulmonary Diseases: Addressing the Need for Precise Drug Delivery.

Respiratory diseases are a major concern in public health, impacting a large population worldwide. Despite the availability of therapies that alleviate symptoms, selectively addressing the critical points of pathopathways remains a major challenge. Innovative formulations designed for reaching these targets within the airways, enhanced selectivity, and prolonged therapeutic effects offer promising solutions. To provide insights into the specific medical requirements of chronic respiratory diseases, the initial focus of this chapter is directed on lung physiology, emphasizing the significance of lung barriers. Current treatments involving small molecules and the potential of gene therapy are also discussed. Additionally, we will explore targeting approaches, with a particular emphasis on nanoparticles, comparing targeted and non-targeted formulations for pulmonary administration. Finally, the potential of inhaled sphingolipids in the context of respiratory diseases is briefly discussed, highlighting their promising prospects in the field.

Protein corona investigations of polyplexes with varying hydrophobicity - From method development to in vitro studies.

In the field of non-viral drug delivery, polyplexes (PXs) represent an advanced investigated and highly promising tool for the delivery of nucleic acids. Upon encountering physiological fluids, they adsorb biological molecules to form a protein corona (PC), that influence PXs biodistribution, transfection efficiencies and targeting abilities. In an effort to understand protein - PX interactions and the effect of PX material on corona composition, we utilized cationic branched 10 kDa polyethyleneimine (b-PEI) and a hydrophobically modified nylon-3 polymer (NM0.2/CP0.8) within this study to develop appropriate methods for PC investigations. A centrifugation procedure for isolating hard corona - PX complexes (PCPXs) from soft corona proteins after incubating the PXs in fetal bovine serum (FBS) for PC formation was successfully optimized and the identification of proteins by a liquid chromatography-tandem mass spectrometry (LC-MS-MS) method clearly demonstrated that the PC composition is affected by the underlying PXs material. With regard to especially interesting functional proteins, which might be able to induce active targeting effects, several candidates could be detected on b-PEI and NM0.2/CP0.8 PXs. These results are of high interest to better understand how the design of PXs impacts the PC composition and subsequently PCPXs-cell interactions to enable precise adjustment of PXs for targeted drug delivery.

Shaping the future from the small scale: dry powder inhalation of CRISPR-Cas9 lipid nanoparticles for the treatment of lung diseases.

INTRODUCTION: Most lung diseases are serious conditions resulting from genetic and environmental causes associated with high mortality and severe symptoms. Currently, treatments available have a palliative effect and many targets are still considered undruggable. Gene therapy stands as an attractive approach to offering innovative therapeutic solutions. CRISPRCas9 has established a remarkable potential for genome editing with high selectivity to targeted mutations. To ensure high efficacy with minimum systemic exposure, the delivery and administration route are key components that must be investigated. AREAS COVERED: This review is focused on the delivery of CRISPRCas9 to the lungs, taking advantage of lipid nanoparticles (LNPs), the most clinically advanced nucleic acid carriers. We also aim to highlight the benefits of pulmonary administration as a local delivery route and the use of spray drying to prepare stable nucleic-acid-based dry powder formulations that can overcome multiple lung barriers. EXPERT OPINION: Exploring the pulmonary administration to deliver CRISPRCas9 loaded in LNPs as a dry powder increases the chances to achieve high efficacy and reduced adverse effects. CRISPRCas9 loaded in LNP-embedded microparticles has not yet been reported in the literature but has the potential to reach and accumulate in target cells in the lung, thus, enhancing overall efficacy and safety.

A Systematic Review of Drug-Carrying Nanosystems Used in the Treatment of Leishmaniasis.

Leishmaniasis is an infectious disease responsible for a huge rate of morbidity and mortality in humans. Chemotherapy consists of the use of pentavalent antimonial, amphotericin B, pentamidine, miltefosine, and paromomycin. However, these drugs are associated with some drawbacks such as high toxicity, administration by parenteral route, and most seriously the resistance of some strains of the parasite to them. Several strategies have been used to increase the therapeutic index and reduce the toxic effects of these drugs. Among them, the use of nanosystems that have great potential as a site-specific drug delivery system stands out. This review aims to compile results from studies that were carried out using first- and second-line antileishmanial drug-carrying nanosystems. The articles referred to here were published between 2011 and 2021. This study shows the promise of effective applicability of drug-carrying nanosystems in the field of antileishmanial therapeutics, with the perspective of providing better patient adherence to treatment, increased therapeutic efficacy, reduced toxicity of conventional drugs, as well as the potential to efficiently improve the treatment of leishmaniasis.

Development, validation and application of a gas chromatography method for the determination of dillapiole from Piper aduncum essential oil in skin permeation samples.

The essential oil extracted from the leaves of Piper aduncum has antifungal, insecticidal and antibacterial activity. Studies with its main compound, dillapiole (DIL) revealed antibacterial and anti-inflammatory potential. Despite all this bioactivity, there is no updated report on the development and validation of analytical and bioanalytical methodology to quantify DIL in skin samples. A selective, precise, accurate and adequate method for the determination of DIL in solutions, porcine ear skin samples and receptor fluid was developed and validated by headspace extraction-gas chromatography with flame ionization detection (HS-GC-FID). HS-GC-FID was applied to determine DIL in Franz cell permeation and retention studies using porcine ear skin samples. In the HS-GC-FID method, matrix-related interferences were not observed at the peak of the DIL retention time. The results showed a high recovery (>97%) after the extraction procedure, allowing the quantification of DIL in complex matrices. In vitro permeation/retention for DIL showed cumulative amounts permeated in the order: receptor fluid (21.98 ± 1.19 µg/cm2 ) > epidermis (15.40 ± 1.20 µg/cm2 ) > dermis (9.52 ± 1.13 µg/cm2 ). HS-GC-FID was successfully validated and the results point to DIL transdermal permeation and to the potential to develop pharmaceutical formulations for skin delivery to treat inflammation or infections.

Piper aduncum Essential Oil Rich in Dillapiole: Development of Hydrogel-Thickened Nanoemulsion and Nanostructured Lipid Carrier Intended for Skin Delivery.

The essential oil extracted from the leaves of Piper aduncum, an aromatic plant from the Amazon region, is rich in dillapiole and presents anti-inflammatory activity. In this study, nanoemulsions (NE) and nanostructured lipid carriers (NLC), which are biocompatible nanostructured systems of a lipid nature, were prepared by high-pressure homogenization for the yet unexplored skin delivery of dillapiole. The addition of hydroxyethylcellulose produced hydrogel-thickened NE or NLC in view to improving the viscosity and skin adherence of the nanoformulations. Formulations were characterized with respect to dillapiole content, droplet size, polydispersity index, zeta potential, morphology, rheological behavior, bioadhesion, skin permeation profile, and in vitro irritancy (HET-CAM). The formulations developed presented spherical, homogeneous nanometric particle size (around 130 nm), narrow polydispersity index (<0.3), and negative zeta potential (around −40 mV). Dillapiole content was slightly lower in NLC compared to NE since the production process involves heating. The hydrogels containing nanocarriers showed pseudoplastic behavior with bioadhesive characteristics. The developed formulations exhibited a controlled release profile, dillapiole delivery up to the dermis, the layer of interest for anti-inflammatory potential, and low irritant potential in the chorioallantoic membrane (HET-CAM). Both hydrogels-thickened NE and NLC seemed to be promising formulations for skin delivery of Piper aduncum essential oil.

Cyclodextrin⁻Drug Inclusion Complexes: In Vivo and In Vitro Approaches.

This review aims to provide a critical review of the biological performance of natural and synthetic substances complexed with cyclodextrins, highlighting: (i) inclusion complexes with cyclodextrins and their biological studies in vitro and in vivo; (ii) Evaluation and comparison of the bioactive efficacy of complexed and non-complexed substances; (iii) Chemical and biological performance tests of inclusion complexes, aimed at the development of new pharmaceutical products. Based on the evidence presented in the review, it is clear that cyclodextrins play a vital role in the development of inclusion complexes which promote improvements in the chemical and biological properties of the complexed active principles, as well as providing improved solubility and aqueous stability. Although the literature shows the importance of their ability to help produce innovative biotechnological substances, we still need more studies to develop and expand their therapeutic properties. It is, therefore, very important to gather together evidence of the effectiveness of inclusion complexes with cyclodextrins in order to facilitate a better understanding of research on this topic and encourage further studies.

Functionalized rifampicin-loaded nanostructured lipid carriers enhance macrophages uptake and antimycobacterial activity.

Tuberculosis is an infectious bacterial disease that causes millions of deaths worldwide. Current treatment recommended by WHO is effective, however it is an extensive and arduous process associated to severe adverse effects, which induces a low patient compliance and the emerging of multidrug resistant tuberculosis. Thus, as a main goal of this study, rifampicin nanoparticles were surface functionalized with a tuftsin-modifed peptide to selectively recognize receptors located on infected alveolar macrophages, enhancing nanoparticles uptake by these cells and improving antimycobacterial activity. A tuftsin-based modified peptide was synthesized and successfully attached to nanoparticles interface (NP-pRIF). In parallel, nanoparticles without peptide were also developed for comparison (NP-RIF). Physicochemical characterization demonstrated that stable and monodisperse nanodelivery systems were obtained, with a controlled drug release profile and non-cytotoxic potential. Moreover, nanoparticles containing peptide were significantly more internalized by macrophages than nanoparticles without peptide over a wide range of time. Both nanoparticles were 2-fold more effective against M. tuberculosis than free rifampicin, suggesting NP-pRIF as a promising strategy for the management of tuberculosis treatment.

Reliability of biceps femoris and semitendinosus muscle architecture measurements obtained with ultrasonography

Introduction Currently, little attention is given to the muscle architecture reliability studies of the hamstring using a robust statistical. Our purpose was to determine the reliability of ultrasound measurements of muscle thickness, fascicle length and pennation angle of the biceps femoris and semitendinosus muscles, including heteroskedasticity and internal consistency analyses. Methods Two images of biceps femoris and semitendinosus at 50% of the thigh length were acquired from 21 volunteers, in two visits. The parameters were measured three times in each image, and for each muscle. The reliability was analyzed by the intraclass correlation coefficient (ICC) and Cronbach’s alpha (αCronbach). The relative standard error of the measurements (%SEM) were calculated and Bland-Altman plots were generated. Results All parameters presented excellent ICC for the three repeated measurements (ICC from 0.93 ‒ 0.99) and moderate to excellent reliability intraday (ICC from 0.70 ‒ 0.95) for both muscles. The present study indicates that ultrasound is a reliable tool to estimate the biceps femoris fascicle length (ICC = 0.97, αCronbach = 0.98, %SEM = 7.86) and semitendinosus (ICC = 0.90, αCronbach = 0.95, %SEM = 7.55), as well as the biceps femoris muscle thickness (ICC = 0.89, αCronbach = 0.94, %SEM = 10.23) and semitendinosus muscle thickness (ICC = 0.87, αCronbach = 0.93, %SEM = 1.35). At last, biceps femoris pennation angle (ICC = 0.93, αCronbach = 0.96 and %SEM = 4.36) and semitendinosus (ICC = 0.96, αCronbach = 0.98 and %SEM = 4.25) also had good repeatability. Conclusion Ultrasonography show good repeatability in estimating of muscle architecture parameters.

Acute Effects of Different Methods of Stretching and Specific Warm-ups on Muscle Architecture and Strength Performance.

Sá, MA, Matta, TT, Carneiro, SP, Araujo, CO, Novaes, JS, and Oliveira, LF. Acute effects of different methods of stretching and specific warm-ups on muscle architecture and strength performance. J Strength Cond Res 30(8): 2324-2329, 2016-The purpose of the study was to investigate the acute effects of 2 stretching interventions, proprioceptive neuromuscular facilitation (PNF) and passive static stretching (PSS), and a specific warm-up (SW) on the strength and architecture of the vastus laterallis and biceps femoris muscles in a subsequent performance on a strength training session (STS). Musculoskeletal ultrasound images were acquired from 9 men before and immediately after stretchings or a SW, and 10 minutes after a STS. The STS consisted of the following exercises: leg extension, leg curl, leg press, and hack machine squat. The PNF resulted in lower performance for all situations. The PSS and SW improved performance for the leg press compared with the PNF and controls (CSs). For the hack machine squat, SWs resulted in higher performance than stretching conditions. The vastus lateralis muscle fascicle length (FL) increases after a STS for PNF. The biceps femoris muscle showed a higher pennation angle 10 minutes after the STS for PSS; the FL increases immediately after PSS and then decreases 10 minutes after the STS for PSS. As per our results, the SWs should be performed before STSs, whereas PNF stretching should not be prescribed because this condition impairs subsequent performance. These results may assist health professionals in prescribing resistance training.

Feasability of a new process to produce fast disintegrating pellets as novel multiparticulate dosage form for pediatric use.

Novel orally disintegrating system based on multiparticulate form was developed, offering an alternative to encounter major issues in the design of dosage form for pediatric patients, i.e., the difficulty in swallowing large solid dosage form (tablet or capsule), and the requirement to cover a broad range of doses for different age groups. Microcrystalline cellulose-based pellets containing acetaminophen were prepared via extrusion/spheronization followed by freeze-drying. The in vitro disintegration behavior of these pellets was quantitatively measured with a texture analyzer. Mercury intrusion and gas adsorption techniques, scanning electron microscopy of pellet surface and cross-section were performed in order to characterize their internal porous structure. Pellets characteristics such as size distribution, sphericity, friability and drug release were also determined. The developing process was able to produce pellets containing high drug loading (25, 50 and up to 75%, w/w) with good sphericity (aspect ratio ∼1) and low friability. The pellets exhibited an instantaneous disintegration upon contact with water, which was indicated by two parameters: the disintegration onset was approximating to 0, and the disintegration time less than 5s. The fast disintegration behavior is correlated with the pellet internal structure characterized by a capillary network with pore diameter varying from 0.1 to 10µm. Such a structure not only ensured a rapid disintegration but it also offers to freeze-dried pellets adequate mechanical properties in comparison with conventional freeze-dried forms. Due to pellet disintegration, fast dissolution of acetaminophen was achieved, i.e., more than 90% of drug released within 15min. This novel multiparticulate system offers novel age-appropriate dosage form for pediatric population owing to their facility of administration (fast disintegration) and dosing flexibility (divided and reduced-size solid form).

Evaluation of short cycles of ultrasound application in nanoemulsions to obtain nanocapsules.

Ultrasound is widely used in several chemical reactions and other process, including production of nanocapsules by in situ polymerization. In this work, the main objective was to evaluate the impacts and viability of successive ultrasound application in nanoemulsions to obtain nanocapsules. Initiator potassium persulfate (KPS) concentration, number of ultrasound cycles and reaction time influences on polymerization efficiency and droplet size were evaluated. This work revealed the successful in situ production of nanocapsules using successive shorts cycles of ultrasound. Number of cycles was the only parameter that not exerted significant influence in polymerization yield. Particle size decay was observed in all nanoemulsions after the first ultrasound application, the same was not observed in further cycles. Gravimetric assessment showed remarkable increase of monomer conversion, indicating that once started polymerization continued at least until 28 days after ultrasound application. Concluding, ultrasound short cycles can be used with no harm to formulation, if carefully performed and, furthermore is a potential cost-effective route for polymerization reactions.

Assessment of muscle architecture of the biceps femoris and vastus lateralis by ultrasound after a chronic stretching program.

OBJECTIVE: To evaluate the chronic effects of a static stretching program on the muscle architecture of biceps femoris (BF) and vastus lateralis (VL) muscles in ultrasound (US) images. DESIGN: Randomized controlled longitudinal trial. SETTING: Biomechanics Laboratory of Physical Education School of the Army, Rio de Janeiro, Brazil. PARTICIPANTS: The study included 24 healthy and physically active male volunteers (19.05 ± 1.40 years, 1.73 ± 0.07 m, and 73.15 ± 8.33 kg), randomly allocated to 1 of 2 groups: stretching group (SG, n = 12) and control group (n = 12). INTERVENTIONS: The SG was submitted to 3 sets of 30 seconds of static stretching 3 times a week during 8 weeks. MAIN OUTCOME MEASURES: Ultrasound equipment (7.5 MHz) was used for the evaluation of BF and VL muscle architecture variables (pennation angle, fiber length, muscle thickness, and fascicle displacement) before and after training. Knee range of motion (ROM) and isometric flexion and extension torque (TQ) were also measured. RESULTS: There were no significant changes in muscle architecture, TQ, and maximum knee flexion angle (P > 0.05). However, maximum knee extension angle (MEA) increased significantly in the SG (pretraining: 159.37 ± 7.27 degrees and posttraining: 168.9 ± 3.7 degrees; P < 0.05). CONCLUSIONS: Volume or intensity (or both) of the stretching protocol was insufficient to cause structural changes in the VL and BF muscles. The increase in MEA could not be explained by muscle architecture changes. CLINICAL RELEVANCE: To describe changes in the VL and BF muscle tendon unit using US after a long-term stretching program to identify which structures are responsible for ROM increase.

Preparation and in vitro evaluation of α and ß-amyrins loaded nanoemulsions.

The triterpenes α- and ß-amyrins display important pharmacological activities. As a result of their high hydrophobia, they present low water solubility and reflect poor oral bioavailability. Different techniques can be used for the improvement of amyrins solubility, one of them is the use of nanoemulsions. Therefore, the method of direct emulsification was used to develop a nanoemulsion of these triterpenes and the resulting drug delivery system was characterized by an in vitro release assay. Encapsulation efficiency higher than 99% was achieved with total release around 30% in 24 h, which suggests that this system could be useful for the administration of α- and ß-amyrins by different routes in an efficient way.