ABSTRACT
Stimuli-responsive nanomaterials have emerged as a promising strategy for inclusion in anticancer therapy. In particular, pH-responsive silica nanocarriers have been studied to provide controlled drug delivery in acidic tumor microenvironments. However, the intracellular microenvironment that the nanosystem must face has an impact on the anticancer effect; therefore, the design of the nanocarrier and the mechanisms that govern drug release play a crucial role in optimizing efficacy. Here, we synthesized and characterized mesoporous silica nanoparticles with transferrin conjugated on their surface via a pH-sensitive imine bond (MSN-Tf) to assess camptothecin (CPT) loading and release. The results showed that CPT-loaded MSN-Tf (MSN-Tf@CPT) had a size of ca. 90 nm, a zeta potential of -18.9 mV, and a loaded content of 13.4%. The release kinetic data best fit a first-order model, and the predominant mechanism was Fickian diffusion. Additionally, a three-parameter model demonstrated the drug-matrix interaction and impact of transferrin in controlling the release of CPT from the nanocarrier. Taken together, these results provide new insights into the behavior of a hydrophobic drug released from a pH-sensitive nanosystem.
ABSTRACT
Lipid nanocarriers have a great potential for improving the physicochemical characteristics and behavior of poorly water-soluble drugs, such as aqueous dispersibility and oral bioavailability. This investigation presents a novel nanostructured lipid carrier (NLC) based on a mixture of solid lipid glycerides, fatty acid esters of PEG 1500 (Gelucire® 44/14), and an oil mix composed of capric and caprylic triglycerides (Miglyol® 812). These NLCs were developed by a simple low-energy method based on melt emulsification to yield highly encapsulating and narrowly distributed nanoparticles (~100 nm, PdI = 0.1, and zeta potential = ~-10 mV). Rhodamine 123 was selected as a poorly water-soluble drug model and owing to its spectroscopic properties. The novel NLCs were characterized by dynamic light scattering (DLS), zeta potential, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), and colloidal stability. The drug release was determined through a dialysis bag and vertical Franzs' cells to provide insights about the methods' suitability, revealing similar performance regardless of their different fluid dynamics. Rhodamine 123 followed a characteristic biphasic release profile owing to the swelling of the hydrophilic polymer coating and diffusion process from the lipid core as revealed by the Korsmeyers-Peppas kinetic modeling. Moreover, to elucidate the formation and incorporation of Rhodamine 123 into the NLC core, several molecular dynamics simulations were conducted. The temperature was shown to be an important condition to improve the formation of the nanoparticles. In addition, the liquid lipid incorporation to the formulation forms nanoparticles with imperfect centers, in contrast to nanoparticles without it. Moreover, Miglyol® 812 improves hydrophobic molecule solubility. These results suggest the potential of novel NLC as a drug delivery system for poorly water-soluble drugs.
ABSTRACT
High-energy methods for the manufacturing of nanomedicines are widely used; however, interest in low-energy methods is increasing due to their simplicity, better control over the process, and energy-saving characteristics during upscaling. Here, we developed a novel lipid-core micelle (LCM) as a nanocarrier to encapsulate a poorly water-soluble drug, nifedipine (NFD), by hot-melt emulsification, a low-energy method. LCMs are self-assembling colloidal particles composed of a hydrophobic core and a hydrophilic shell. Hybrid materials, such as Gelucire 44/14, are thus excellent candidates for their preparation. We characterized the obtained nanocarriers for their colloidal properties, drug loading and encapsulation efficiency, liquid state, stability, and drug release. The low-energy method hot-melt emulsification was successfully adapted for the manufacturing of small and narrowly dispersed LCMs. The obtained LCMs had a small average size of ~ 11 nm and a narrow polydispersity index (PDI) of 0.228. These nanocarriers were able to increase the amount of NFD dispersible in water more than 700-fold. Due to their sustained drug release profile and the PEGylation of Gelucire 44/14, these nanocarriers represent an excellent starting point for the development of drug delivery systems designed for long circulation times and passive targeting.
Subject(s)
Drug Carriers/chemistry , Lipids/chemistry , Nifedipine/chemistry , Delayed-Action Preparations , Drug Compounding/methods , Hydrophobic and Hydrophilic Interactions , Micelles , Nanoparticles/chemistry , Particle SizeABSTRACT
ResumenObjetivo general: Describir la percepción de paciente y familia sobre la seguridad de la atención sanitaria brindada en un Hospital Universitario colombiano de alta complejidad durante su proceso de hospitalización.MetodologíaEstudio cuantitativo con abordaje descriptivo-transversal y muestreo estratificado no aleatorizado, con una muestra de 276 participantes de los servicios de hospitalización y urgencias; la recolección de datos se hizo con el cuestionario "Percepción de seguridad de la atención en salud en el ámbito hospitalario".ResultadosLas dimensiones indagadas fueron: 1. Información recibida por los pacientes con 88.8% de acuerdo; 2. Calidad en la atención en salud recibida con 88.2% de acuerdo; 3. El 97.2% no identificaron Eventos Adversos; 4. El 99,64% no identificaron incidentes en la atención de salud; y 5. Sensación de seguridad percibida en el 88,77% como segura y en el 4,35% como ligeramente segura. Discusión y conclusionesSe encontró una alta percepción positiva de la seguridad en la atención de salud brindada y baja cantidad de eventos adversos e incidentes, el comportamiento de los resultados fue en general similar entre las 3 categorías de participantes (paciente y cuidador, paciente únicamente y cuidador familiar únicamente) y por servicios participantes. Lo anterior muestra la importancia de implementar y mantener estrategias institucionales que van desde policitas, programas, procedimientos y actividades específicas en los servicios para que el paciente y su familia se sientan seguros frente a su situación de salud y tratamiento
AbstractObjective: To describe the patients and families Ì perception on the safety of health care provided at a highly complex Colombian University Hospital during the hospitalization process.Methodology: It was used a quantitative study with descriptive-transversal approach and non-randomized stratified sampling, with a sample of 276 participants from the hospitalization and emergency services. The data collection was done with the questionnaire "Perception of safety of health care in the hospital setting".Results: The dimensions investigated were: 1. Information received by patients with 88.8% of agreement; 2. Quality in health care received with 88.2% of agreement; 3. 97.2% did not identify adverse events; 4. 99.64% did not identify incidents in health care; and 5. Feeling of safety perceived by 88.77% as safe and at 4.35% as slightly safe.Discussion and conclusions: It was found a high positive perception of safety in health care provided and low number of adverse events and incidents. The behavior of the results was generally similar among the 3 categories of participants (patient and caregiver, patient only and family caregiver only) and by participating services. This shows the importance of implementing and maintaining institutional strategies that go from policies, programs, procedures and specific activities in the services so that patients and their families feel safe in front of their health situation and treatment
