Lipid-core nanoparticles: Classification, preparation methods, routes of administration and recent advances in cancer treatment

Nanotechnological drug delivery platforms represent a new paradigm for cancer therapeutics as they improve the pharmacokinetic profile and distribution of chemotherapeutic agents over conventional formulations. Among nanoparticles, lipid-based nanoplatforms possessing a lipid core, that is, lipid-core nanoparticles (LCNPs), have gained increasing interest due to lipid properties such as high solubilizing potential, versatility, biocompatibility, and biodegradability. However, due to the wide spectrum of morphologies and types of LCNPs, there is a lack of consensus regarding their terminology and classification. According to the current state-of-the-art in this critical review, LCNPs are defined and classified based on the state of their lipidic components in liquid lipid nanoparticles (LLNs). These include lipid nanoemulsions (LNEs) and lipid nanocapsules (LNCs), solid lipid nanoparticles (SLNs) and nanostructured lipid nanocarriers (NLCs). In addition, we present a comprehensive and comparative description of the methods employed for their preparation, routes of administration and the fundamental role of physicochemical properties of LCNPs for efficient antitumoral drug-delivery application. Market available LCNPs, clinical trials and preclinical in vivo studies of promising LCNPs as potential treatments for different cancer pathologies are summarized.MCIN/AEI FPU18/05336European Social Fund (ESF)Ph.D. program of Biomedicine of the University of GranadaMCIN/AEI/FEDER "Una manera de hacer Europa" RTI2018.101309B-C21 RTI2018.101309B-C2

Effects of the ActiveHip+ mHealth intervention on the recovery of older adults with hip fracture and their family caregivers:a multicentre open-label randomised controlled trial

Background: Mobile health (mHealth) systems are a promising alternative for rehabilitation of hip fracture, addressing constrained healthcare resources. Half of older adults fails to recover their pre-fracture routines, which imposes a burden on caregivers. We aimed to test the effectiveness of the 3-month ActiveHip + mHealth intervention on physical and psychological outcomes of older adults with hip fracture and their family caregivers. Methods: In a multicentre open-label randomised controlled trial conducted across 3 hospitals in Andalusia (Spain), patients older than 65 with a hip fracture, who were previously independent and lacked cognitive impairment were recruited alongside with their caregivers. Participants were randomly allocated (1:1) to the intervention group (ActiveHip+) or control (usual care) group. The intervention group underwent a 12-week health education and tele-rehabilitation programme through the ActiveHip + mHealth intervention. The primary outcome, physical performance, was assessed using the Short Physical Performance Battery at three time points: at hospital discharge (baseline), 3-month after surgery (post intervention) and 1-year after surgery follow-up. Primary analyses of primary outcomes and safety data followed an intention-to-treat approach. This study is registered at ClinicalTrials.gov, NCT04859309. Findings: Between June 1st, 2021 and June 30th, 2022 data from 105 patients and their caregivers were analysed. Patients engaged in the ActiveHip + mHealth intervention (mean 7.11 points, SE 0.33) showed higher physical performance compared with patients allocated in the control group (mean 5.71 points, SE 0.32) at 3 months after surgery (mean difference in change from baseline 1.40 points, SE 0.36; puncorrected = 0.00011). These benefits were not maintained at 1-year after surgery follow-up (mean difference in change from baseline 0.19 points, SE 0.47; puncorrected = 0.68). No adverse events, including falls and refractures, were reported during the tele-rehabilitation sessions. At 3-months, the intervention group had 2 falls, compared to 4 in the control group, with no observed refractures. At the 1-year follow-up, the intervention group experienced 7 falls and 1 refracture, while the control group had 13 falls and 2 refractures. Interpretation: This study suggests that the ActiveHip + mHealth intervention may be effective for recovering physical performance in older adults with hip fracture. Importantly, the implementation of ActiveHip + into daily clinical practice may be feasible and has already been adopted in 18 hospitals, mostly in Spain but also in Belgium and Portugal. Thus, ActiveHip + could offer a promising solution when rehabilitation resources are limited. However, its dependence on caregiver support and the exclusion of participants with cognitive impairment makes it necessary to be cautious about its applicability. In addition, the non-maintenance of the effectiveness at 1-year follow-up highlights the need of refinement the ActiveHip + intervention to promote long-lasting behavioural changes. Funding: EIT Health and the Ramón y Cajal 2021 Excellence Research Grant action from the Spanish Ministry of Science and Innovation.</p

Maslinic Acid Nanoparticles: A Drug to Carry Others

Maslinic acid (MA), a triterpene widely found in natural sources, is a compound which is gaining interest due to its multiple therapeutic activities and its lack of harmful effects. However, MA is practically insoluble in water, which limits its clinical application. Here, we present a solvent displacement method to produce MA Solid Lipid Nanoparticles (SLNs) as a nanoplatform to carry hydrophobic drugs. A systematic study of the experimental parameters that may have some influence on the colloidal characteristics of MA SLNs was carried out. The effect of the aqueous/organic phase volume ratio and the organic phase composition on the size of SLNs evidence the role of the solvent diffusivity on the colloidal characteristic of the SLNs. On the other hand, the effect of surfactant/MA ratio proved the relevance of the surfactant on stabilizing the SLNs interface, owing to the changes on the interfacial tension that it promotes. MA SLNs have proved to be highly stable over time and in a wide range of pH and salinity conditions, as well as having a high curcumin encapsulation efficiency. The MA SLNs prepared in this work provide a starting point to develop functionalized active nanocarriers which allow establishing a synergistic relation with the loaded drug

Effect of the Protein Corona Formation on Antibody Functionalized Liquid Lipid Nanocarriers

The main aim of this study is to report basic knowledge on how a protein corona (PC) could affect or modify the way in which multifunctionalized nanoparticles interact with cells. With this purpose, we have firstly optimized the development of a target-specific nanocarrier by coupling a specific fluorescent antibody on the surface of functionalized lipid liquid nanocapsules (LLNCs). Thus, an anti-HER2-FITC antibody (αHER2) has been used, HER2 being a surface receptor that is overexpressed in several tumor cells. Subsequently, the in vitro formation of a PC has been developed using fetal bovine serum supplemented with human fibrinogen. Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA), Laser Doppler Electrophoresis (LDE), and Gel Chromatography techniques have been used to assure a complete physico-chemical characterization of the nano-complexes with (LLNCs-αHER2-PC) and without (LLNCs-αHER2) the surrounding PC. In addition, cellular assays were performed to study the cellular uptake and the specific cellular-nanocarrier interactions using the SKBR3 (high expression of HER2) breast cancer cell line and human dermal fibroblasts (HDFa) (healthy cell line without expression of HER2 receptors as control), showing that the SKBR3 cell line had a higher transport rate (50-fold) than HDFa at 60 min with LLNCs-αHER2. Moreover, the SKBR3 cell line incubated with LLNCs-αHER2-PC suffered a significant reduction (40%) in the uptake. These results suggest that the formation of a PC onto LLNCs does not prevent specific cell targeting, although it does have an important influence on cell uptake.FEDER/Junta de Andalucía-Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Projects PY20_00241 and A-FQM-90-UGR20MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” for funding the PID2022-140151OB-C21 and PID2022-140151OB-C22 projects and the Chair “Doctors Galera-Requena in cancer stem cell research

Maslinic acid solid lipid nanoparticles as hydrophobic anticancer drug carriers: Formulation, in vitro activity and in vivo biodistribution

Maslinic acid (MA) is a natural pentacyclic triterpenoid with inherent antitumor activity which has a very low solubility in water. MA solid lipid nanoparticles (SLNs) were prepared using Poloxamer 407 and Dicarboxylic acid-Poloxamer 407 as surfactants. Both MA SLNs are monodisperse, with sizes around 130 nm, and stable. Curcumin has been encapsulated in both types of nanoparticles without altering their colloidal properties. Moreover, SLNs greatly improve the solubility of MA and Curcumin. The cytotoxicity of MA and SLNs has been evaluated in BxPC3 human pancreatic cancer cells, MCF7 human breast cancer cells, and in a human fibroblast primary cell line. MA shows higher cytotoxic effect in BxPC3 and MCF7 cancer cells than in human primary fibroblasts. Nile Red loaded MA SLNs are quickly uptaken by BxPC3 and MCF7 cells, and show different cytoplasmic distributions depending on the cellular line. The oral or intravenous administration of MA SLNs in mice does not report any toxic effect, and the intravenous administration of fluorescent MA SLNs shows a homogeneous distribution in mice, without site-specific accumulation. Results suggest the great potential of MA SLNs as nanocarriers of anticancer drugs and as promising targeted theranostic nanodevices

Effects of Tele-Rehabilitation Compared with Home-Based in-Person Rehabilitation for Older Adult’s Function after Hip Fracture

This study aimed to examine the effect of a multidisciplinary tele-rehabilitation program on functional recovery of older adults with hip fracture compared with home-based in-person rehabilitation. In this single-blinded, non-randomized clinical trial, we included older with hip fracture. The tele-rehabilitation group received a 12-week tele-rehabilitation program (supervised by their family caregivers). The control group received the usual postoperative rehabilitation provided by the Andalusian health system (Spain). The primary outcome was the patient-reported functional status assessed with the Functional Independence Measure. We also measured performance-based functional recovery using the Timed Up and Go Test and Short Physical Performance Battery. We performed both a per-protocol (62 participants; 28 tele-rehabilitation and 34 control groups) and an intention-to-treat analysis (71 participants; 35 tele-rehabilitation and 36 control groups). Participants who used the tele-rehabilitation program had higher Functional Independence Measure scores (high effect size: 0.98 Cohen’s d; p < 0.001) and better performance in the Timed Up and Go Test (medium effect size: 0.63 Cohen’s d; p = 0.025) compared with the control group. Differences between groups post-intervention were not statistically significant in the Short Physical Performance Battery. The tele-rehabilitation intervention proposed in this study is a valuable treatment option in the recovery process for older adults with hip fracture. ClinicalTrials.gov Identifier: NCT02968589.Medicine, Faculty ofOther UBCNon UBCFamily Practice, Department ofReviewedFacult

An m-Health telerehabilitation and health education program on physical performance in patients with hip fracture and their family caregivers: Study protocol for the ActiveHip+ randomized controlled trial

Telerehabilitation interventions administered via a smartphone may provide new feasible and effective rehabilitation options at home for patients with hip fracture. However, to date, no such interventions have been shown to be effective in the recovery key health outcomes of these patients. The present multicentre randomized controlled trial (RCT) aims to test the effect of the ActiveHip+ m-Health system in the recovery of physical performance, functional level, quality of life, and other health-related outcomes in both patients with hip fracture and their family caregivers. A total of 104 patients older than 65 years, with hip fracture, and their family caregivers will be randomized into the ActiveHip+ rehabilitation (N = 52) or the control group (N = 52). ActiveHip+ is a 12-week smartphone-based rehabilitation program conducted in Granada and Cádiz (Spain) that includes: (1) 24 sessions of physical exercise and 12 sessions of occupational therapy; (2) seven educational modules for patients and for caregivers; and (3) general recommendations in activities of daily living. The control group will receive the usual rehabilitation protocol offered by the Andalusian Public Healthcare System. The primary outcome is the patient's physical performance, while the secondary outcomes are the patient's functional level, quality of life, pain, fear of falling, fitness perception, pre-fracture functional level, emotional status, and caregiver burden. The present project will substantially contribute to the existing knowledge by testing for the first time the efficacy and feasibility of a multidisciplinary m-Health system in the rehabilitation of patients with hip fracture

Ansiedad, depresión, somatizaciones : proceso asistencial integrado. 2ª ed

Publicado en la página web de la Consejería de Salud: www.juntadeandalucia.es/salud (Consejería de Salud / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)YesLa propuesta de la Consejería de Salud,en 2001, de dar prioridad a la descripción del Proceso Asistencial Integrado Ansiedad, Depresión, Somatizaciones (PAI-ADS) supuso una importante innovación en el modelo de servicios para la atención a estos problemas de salud desde el Sistema Sanitario Público de Andalucía (SSPA). La revisión de la primera edición de este proceso pretende ser un instrumento de trabajo que pueda enriquecerse en su aplicación con las aportaciones de todos los profesionales comprometidos con la mejora continua de la atención a la salud mental de la población. Se apoya en los resultados de la puesta en marcha del modelo de cooperación que se ha llevado a cabo durante estos 10 años, en toda la geografía andaluza, y pretende clarificar los recorridos de los pacientes en todas las modalidade