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In disease treatment, maintaining therapeutic drug concentrations often requires multiple doses. Lipid/polymer hybrid nanoparticles (LPHNPs) offer a promising solution by facilitating sustained drug delivery within therapeutic ranges. Here, we synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with soy lecithin using nanoprecipitation and self-assembly techniques. These nanoparticles were incorporated into gelatin aerogels to ensure uniform distribution and increase the concentration. Our study focused on understanding the release kinetics of hydrophilic (gallic acid) and lipophilic (quercetin) compounds from this system. Nanoparticles exhibited hydrodynamic diameters of 100 ± 15 nm (empty), 153 ± 33 nm (gallic acid-loaded), and 149 ± 21 nm (quercetin-loaded), with encapsulation efficiencies of 90 ± 5% and 70 ± 10% respectively. Gallic acid release followed the Korsmeyer-Peppas kinetics model (n = 1.01), while quercetin showed first-order kinetics. Notably, encapsulated compounds demonstrated delayed release compared to free compounds in gelatin aerogels, illustrating LPHNPs' ability to modulate release profiles independent of the compound type. This study underscores the potential of LPHNPs in optimizing drug delivery strategies for enhanced therapeutic outcomes.

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BACKGROUND: Tissue engineering seeks to improve, maintain, or replace the biological functions of damaged organs or tissues with biological substitutes such as the development of scaffolds. In the case of bone tissue, they must have excellent mechanical properties like native bone. OBJECTIVE: In this work, three geometric models were designed for scaffolds with different structure lattices and porosity that could be biomechanically suitable and support cell growth for trabecular bone replacement applications in tissue engineering and regenerative medicine to the proximal femur area. METHODS: Geometries were designed using computer-aided design (CAD) software and evaluated using finite element analysis in compression tests. Three loads were considered according to the daily activity: 1177 N for slow walking, 2060 N for fast walking, and 245.25 N for a person in a bipedal position. All these loads for an adult weight of 75 kg. For each of them, three biomaterials were assigned: two polymers (poly-glycolic acid (PGA) and poly-lactic acid (PLA)) and one mineral (hydroxyapatite (HA)). 54 tests were performed: 27 for each of the tests. RESULTS: The results showed Young's modulus (E) between 1 and 4 GPa. CONCLUSION: If the resultant E is in the range of 0.1 to 5 GPa, the biomaterial is considered an appropriate alternative for the trabecular bone which is the main component of the proximal bone. However, for the models applied in this study, the best option is the poly-lactic acid which will allow absorbing the acting loads.

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Functionally active aligned fibers are a promising approach to enhance neuro adhesion and guide the extension of neurons for peripheral nerve regeneration. Therefore, the present study developed poly(lactic-co-glycolic acid) (PLGA)-aligned electrospun mats and investigated the synergic effect with carbon nanotubes (CNTs) and Choline Bitartrate ionic liquid (Bio-IL) on PLGA fibers. Morphology, thermal, and mechanical performances were determined as well as the hydrolytic degradation and the cytotoxicity. Results revealed that electrospun mats are composed of highly aligned fibers, and CNTs were aligned and homogeneously distributed into the fibers. Bio-IL changed thermal transition behavior, reduced glass transition temperature (Tg), and favored crystal phase formation. The mechanical properties increased in the presence of CNTs and slightly decreased in the presence of the Bio-IL. The results demonstrated a decrease in the degradation rate in the presence of CNTs, whereas the use of Bio-IL led to an increase in the degradation rate. Cytotoxicity results showed that all the electrospun mats display metabolic activity above 70%, which demonstrates that they are biocompatible. Moreover, superior biocompatibility was observed for the electrospun containing Bio-IL combined with higher amounts of CNTs, showing a high potential to be used in nerve tissue engineering.

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BACKGROUND: Treatment of splenic trauma is currently based on non-surgical treatment or the use of interventional radiology. The conservative surgery of the spleen in splenic trauma remains marginal. OBJECTIVE: To analyze the safety and efficacy of conservative surgical treatment in splenic trauma. METHOD: A retrospective study was performed over a 16-year period with the intention of recording the diagnostic and therapeutic attitude in a second level hospital, focusing on patients who received conservative splenic surgical treatment for splenic trauma, excluding splenectomies and non-surgical treatment. RESULTS: 110 patients presented splenic trauma. Spleen-sparing surgery was performed in 15 patients. The grades of splenic lesions were: 1 patient with grade I, 1 patient with grade II, 7 patients with grade III and 6 patients with grade IV. Surgical treatment was splenorrhaphy in 5 patients (33%), hemostatic agents and polyglycolic acid mesh in 4 (26%), partial splenectomy with placement of polyglycolic acid mesh in 3 (20%), partial splenectomy in 2 (13%), and electrocautery in 1 (6%). None of the patients initially treated with conservative surgery required posterior splenectomy and no patient died. CONCLUSION: We provide evidence supporting the usefulness and safety of conservative splenic surgery in splenic trauma, which would have its place in grades II, III and IV trauma in health centers that do not have urgent interventional radiology.

ANTECEDENTES: El tratamiento del traumatismo esplénico se basa en medidas conservadoras no quirúrgicas o en el uso de radiología intervencionista. La cirugía conservadora del bazo en el traumatismo esplénico sigue siendo inusual. OBJETIVO: El análisis de seguridad y eficacia del tratamiento quirurgico conservador en el traumatismo esplénico. MÉTODO: Se realizó un estudio retrospectivo durante un período de 16 años con la intención de registrar la actitud diagnóstica y terapéutica en un hospital de segundo nivel, enfocándose en los pacientes que recibieron tratamiento quirúrgico conservador esplénico por traumatismo esplénico, excluyendo esplenectomías y tratamientos no quirúrgicos. RESULTADOS: 110 pacientes presentaron traumatismo esplénico. La cirugía conservadora esplénica se realizó en 15 pacientes. Los grados de lesiones esplénicas fueron: 1 paciente con grado I, 1 paciente con grado II, 7 pacientes con grado III y 6 pacientes con grado IV. El tratamiento quirúrgico fue esplenorrafia en 5 pacientes (33%), agentes hemostáticos y malla de ácido poliglicólico en 4 (26%), esplenectomía parcial con colocación de malla de ácido poliglicólico en 3 (20%), esplenectomía parcial en 2 (13%) y hemostasia con electrocauterio en 1 (6%). Ninguno de los pacientes tratados inicialmente con cirugía conservadora requirió esplenectomía posterior y ningún paciente falleció. CONCLUSIONES: La cirugía conservadora esplénica puede ser útil y segura en traumatismos esplénicos, la cual tendría su lugar en traumatismos de grados II, III y IV en centros hospitalarios en los que no se cuente con radiología intervencionista urgente.

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Rivaroxaban (RVX), an oral direct factor Xa inhibitor, is being explored as an alternative to traditional anticoagulans. However, RVX still faces pharmacokinetic limitations and adverse effects, highlighting the need for more effective formulations. In this regard, pharmaceutical nanotechnology, particularly the use of polymeric nanoparticles (PNPs), offers a promising approach for optimizing RVX delivery. This study aimed to develop and physicochemically characterize RVX-loaded poly(lactic-co-glycolic acid) (PLGA)/sodium lauryl sulfate (SLS) or didodecyl dimethylammonium bromide (DMAB) nanoparticles, and also evaluate their pharmacological and toxicological profiles as a potential therapeutic strategy. The PNPs exhibited sizes below 300 nm and spherical morphology, with both negative and positive surface charges, according to surfactant used. They demonstrated high encapsulation efficiency and suitable yields, as well as rapid initial liberation followed by sustained release in different pH environments. Importantly, in vivo evaluations revealed a time-dependent antithrombotic effect surpassing the free form of RVX when administered orally in SLS or DMAB PNP. No hemolytic or cytotoxic effects were observed at various concentrations of the PNPs. Interestingly, the PNPs did not induce hemorrhagic events or cause liver enzyme alterations in vivo. These findings suggest that RVX-loaded SLS or DMAB PNPs are promising innovative therapeutic alternatives for the treatment of thromboembolic diseases.

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Mathematical models are used to characterize and optimize drug release in drug delivery systems (DDS). One of the most widely used DDS is the poly(lactic-co-glycolic acid) (PLGA)-based polymeric matrix owing to its biodegradability, biocompatibility, and easy manipulation of its properties through the manipulation of synthesis processes. Over the years, the Korsmeyer-Peppas model has been the most widely used model for characterizing the release profiles of PLGA DDS. However, owing to the limitations of the Korsmeyer-Peppas model, the Weibull model has emerged as an alternative for the characterization of the release profiles of PLGA polymeric matrices. The purpose of this study was to establish a correlation between the n and ß parameters of the Korsmeyer-Peppas and Weibull models and to use the Weibull model to discern the drug release mechanism. A total of 451 datasets describing the overtime drug release of PLGA-based formulations from 173 scientific articles were fitted to both models. The Korsmeyer-Peppas model had a mean Akaike Information Criteria (AIC) value of 54.52 and an n value of 0.42, while the Weibull model had a mean AIC of 51.99 and a ß value of 0.55, and by using reduced major axis regression values, a high correlation was found between the n and ß values. These results demonstrate the ability of the Weibull model to characterize the release profiles of PLGA-based matrices and the usefulness of the ß parameter for determining the drug release mechanism.

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In previous work, we reported on the design of biodegradable rhein-loaded PLGA microparticles for the treatment of osteoarthritis. Considering that a formulation designed for intra-articular administration must meet sterility requirements to guarantee its safety, in this study the effect of gamma radiation sterilization on these microparticles was evaluated. The size, morphology, and surface characteristics of the microparticles and the encapsulation efficiency of rhein were not affected by the sterilization process. Although DSC and PXRD analyses suggested otherwise, rhein release profiles were not altered by gamma radiation. The release of rhein from the microparticles was fitted to a Gompertz model. In conclusion, the results of this study suggest that gamma radiation is a suitable method for the sterilization of rhein-loaded PLGA microparticles to enable their intra-articular administration in order to provide a therapeutic solution to patients suffering from chronic joint diseases.

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One of the most widely used molecules used for photodynamic therapy (PDT) is 5-aminolevulinic acid (5-ALA), a precursor in the synthesis of tetrapyrroles such as chlorophyll and heme. The 5-ALA skin permeation is considerably reduced due to its hydrophilic characteristics, decreasing its local bioavailability and therapeutic effect. For this reason, five different systems containing polymeric particles of poly [D, L-lactic-co-glycolic acid (PLGA)] were developed to encapsulate 5-ALA based on single and double emulsions methodology. All systems were standardized (according to the volume of reagents and mass of pharmaceutical ingredients) and compared in terms of laboratory scaling up, particle formation and stability over time. UV-VIS spectroscopy revealed that particle absorption/adsorption of 5-ALA was dependent on the method of synthesis. Different size distribution was observed by DLS and NTA techniques, revealing that 5-ALA increased the particle size. The contact angle evaluation showed that the system hydrophobicity was dependent on the surfactant and the 5-ALA contribution. The FTIR results indicated that the type of emulsion influenced the particle formation, as well as allowing PEG functionalization and interaction with 5-ALA. According to the 1H-NMR results, the 5-ALA reduced the T1 values of polyvinyl alcohol (PVA) and PLGA in the double emulsion systems due to the decrease in molecular packing in the hydrophobic region. The results indicated that the system formed by single emulsion containing the combination PVA-PEG presented greater stability with less influence from 5-ALA. This system is a promising candidate to successfully encapsulate 5-ALA and achieve good performance and specificity for in vitro skin cancer treatment.

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This study aimed to investigate biocompatibility, integration, and tissue host response of the Poly (Lactic-co-Glycolic acid) (PLGA)/Poly (isoprene) (PI) epoxidized (PLGA/PIepox) innovative scaffold combined with adipose derived mesenchymal stem cells (ADSC). We implanted the scaffold subcutaneously on the back of 18 female rats and monitored them for up to 14 days. When compared to controls, PLGA/PIepox + ADSC demonstrated an earlier vascularization, a tendency of inflammation reduction, an adequate tissue integration, higher cell proliferation, and a tendency of expression of collagen decreasing. However, 14 days post-implantation we found similar levels of CD31, Ki67 and AE1/AE3 in PLGA/PIepox when compared to control groups. The interesting results, lead us to the assumption that PLGA/PIepox is able to provide an effective delivery system for ADSC on tissue host. This animal study assesses PLGA/PIepox + ADSC in in vivo tissue functionality and validation of use, serving as a proof of concept for future clinical translation as it presents an innovative and promising tissue engineering opportunity for the use in tissue reconstruction.

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Rifampicin is one of the most commonly used antibiotics for treating tuberculosis, but shows low bioavailability and requires long-term administration, and hence its use may result in severe side effects. Encapsulation of rifampicin in polymeric reservoirs allows it to be administered locally and improves its pharmacological action. High rifampicin loading is crucial for obtaining an adequate therapeutic effect. Generally, the drug loading is a complex function of reservoir fabrication parameters. In the current work, we systematically varied the drug (rifampicin), polymer (PLGA) and dispersed phase contents as well as the solvent evaporation rate, particle size and number of particle washing cycles to characterize the challenges involved in encapsulating rifampicin. Physical insight into the low encapsulation efficiencies was provided, as well as an optimization of fabrication conditions to achieve higher drug loading levels. The particle solidification stage was found in the current work to be the most crucial step, where a significant amount of rifampicin was lost enhanced by its solubility in the aqueous medium. Increases in polymer concentration, solvent evaporation rate and particle size each significantly improved the drug loading by hindering of solvent-assisted escape of the drug. Based on our observation of the drug loading being extremely sensitive to the particle recovery and washing procedure after the solvent evaporation, most of the encapsulated rifampicin was concluded to be located on or very near the reservoir surface. Encapsulation could be significantly improved by fabricating multiple emulsions, especially double w/o/w emulsions, but the resultant particles were relatively large and porous, which might be a drawback for drug administration.

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