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.

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.

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.