RESUMO
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.
Assuntos
Ácido Gálico , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Quercetina , Quercetina/química , Nanopartículas/química , Ácido Gálico/química , Cinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Lecitinas/química , Gelatina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Liberação Controlada de Fármacos , Lipídeos/química , Portadores de Fármacos/química , Tamanho da PartículaRESUMO
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.
Assuntos
Desenho Assistido por Computador , Análise de Elementos Finitos , Engenharia Tecidual , Alicerces Teciduais , Alicerces Teciduais/química , Humanos , Engenharia Tecidual/métodos , Durapatita/química , Módulo de Elasticidade , Bioimpressão/métodos , Poliésteres/química , Porosidade , Simulação por Computador , Materiais Biocompatíveis/química , Substitutos Ósseos/química , Ácido Poliglicólico/química , Impressão Tridimensional , Teste de Materiais , Osso e OssosRESUMO
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.
Assuntos
Líquidos Iônicos , Nanotubos de Carbono , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Líquidos Iônicos/farmacologia , Ácido Poliglicólico/química , Ácido Láctico/farmacologia , Ácido Láctico/química , Glicóis , Alicerces TeciduaisRESUMO
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.
Assuntos
Nanopartículas , Ácido Poliglicólico , Ratos , Animais , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Ratos Wistar , Ácido Poliglicólico/química , Dodecilsulfato de Sódio , Rivaroxabana , Brometos , Fibrinolíticos/farmacologia , Ácido Láctico/química , Glicóis , Nanopartículas/química , Tamanho da PartículaRESUMO
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.
Assuntos
Ácido Aminolevulínico , Ácido Poliglicólico , Clorofila , Emulsões , Heme , Ácido Láctico/química , Tamanho da Partícula , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Álcool de Polivinil/química , Tensoativos , TetrapirróisRESUMO
Poly(lactic-co-glycolic acid) is one of the most used polymers for drug delivery systems (DDSs). It shows excellent biocompatibility, biodegradability, and allows spatio-temporal control of the release of a drug by altering its chemistry. In spite of this, few formulations have reached the market. To characterize and optimize the drug release process, mathematical models offer a good alternative as they allow interpreting and predicting experimental findings, saving time and money. However, there is no general model that describes all types of drug release of polymeric DDSs. This study aims to perform a statistical comparison of several mathematical models commonly used in order to find which of them best describes the drug release profile from PLGA particles synthesized by nanoprecipitation method. For this purpose, 40 datasets extracted from scientific articles published since 2016 were collected. Each set was fitted by the models: order zero to fifth order polynomials, Korsmeyer-Peppas, Weibull and Hyperbolic Tangent Function. Some data sets had few observations that do not allow to apply statistic test, thus bootstrap resampling technique was performed. Statistic evidence showed that Hyperbolic Tangent Function model is the one that best fit most of the data.
Assuntos
Ácido Láctico , Ácido Poliglicólico , Sistemas de Liberação de Medicamentos , Glicóis , Cinética , Ácido Láctico/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/químicaRESUMO
This work aimed to synthesize poly (D, L-lactic-co-glycolic acid) (PLGA) microparticles containing hinokinin (HNK) and to evaluate their cytotoxic activity against tumoral SiHa cells and non-tumoral HaCaT cells. Hinokinin was incorporated into PLGA (PLGA-HNK) with an encapsulation efficiency of 84.18 ± 2.32%. PLGA and PLGA-HNK were characterized by SEM microscopy and showed spherical morphology with an average size of â¼3.33. Encapsulation efficiency was determined by a calibration curve using UV-vis spectroscopy. PLGA-HNK more active inhibiting proliferation of SiHa cells (IC50 = 14.68 µM) than free HNK (IC50 = 225.5 µM). In relation to HaCaT cells, PLGA-HNK showed no significant difference compared to the negative control. These results led to an increase in HNK bioavailability and thereby, biological activity. In silico prediction analysis suggests that HNK is cytotoxic against SiHa cells with E6 and MDM2 inhibition as possible main mechanism of action.
Assuntos
Antineoplásicos , Nanopartículas , 4-Butirolactona/análogos & derivados , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzodioxóis , Ácido Láctico/química , Lignanas , Nanopartículas/química , Tamanho da Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido PoliglicólicoRESUMO
A promising alternative to conventional nerve grafting is the use of artificial grafts made from biodegradable and biocompatible materials and support cells. The aim of this study has been to produce a biodegradable nerve conduit and investigate the cytocompatibility with stem cells and its regeneration promoting properties in a rat animal model. A poly (lactic-co-glycolic acid) (PLGA) conduit of aligned nanofibers was produced by the electrospinning method, functionalized with gelatin and seeded either with mouse embryonic stem cells (mESCs) or with human mesenchymal stem cells (SHED). The cell proliferation and viability were analyzed in vitro. The conduits were implanted in a rat model of sciatic nerve lesion by transection. The functional recovery was monitored for 8 weeks using the Sciatic Functional Index (SFI) and histological analyses were used to assess the nerve regeneration. Scaffolds of aligned PLGA fibers with an average diameter of 0.90 ± 0.36 µm and an alignment coefficient of 0.817 ± 0.07 were produced. The treatment with gelatin increased the fiber diameter to 1.05 ± 0.32 µm, reduced the alignment coefficient to 0.655 ± 0.045 and made the scaffold very hydrophilic. The cell viability and Live/dead assay showed that the stem cells remained viable and proliferated after 7 days in culture. Confocal images of phalloidin/DAPI staining showed that the cells adhered and proliferated widely, in fully adaptation with the biomaterial. The SFI values of the group that received the conduit were similar to the values of the control lesioned group. In conclusion, conduits composed of PLGA-gelatin nanofibers were produced and promoted a very good interaction with the stem cells. Although in vitro studies have shown this biomaterial to be a promising biomaterial for the regeneration of nerve tissue, in vivo studies of this graft have not shown significant improvements in nerve regeneration.
Assuntos
Gelatina/química , Nanofibras/química , Regeneração Nervosa/efeitos dos fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/farmacologia , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/fisiologia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Ácido Poliglicólico/química , Ratos , Células de Schwann/citologia , Nervo Isquiático/citologia , Células-Tronco/citologia , Alicerces Teciduais/químicaRESUMO
Bioactive glasses (BG) are known for their ability to bond to bone tissue. However, in critical situations, even the osteogenic properties of BG may be not enough to induce bone consolidation. Thus, the enrichment of BG with polymers such as Poly (D, L-lactic-co-glycolic) acid (PLGA) and associated to photobiomodulation (PBM) may be a promising strategy to promote bone tissue healing. The aim of the present study was to investigate the in vivo performance of PLGA supplemented BG, associated to PBM therapy, using an experimental model of cranial bone defect in rats. Rats were distributed in 4 different groups (Bioglass, Bioglass/PBM, Bioglas/PLGA and BG/PLGA/PBM). After the surgical procedure to induce cranial bone defects, the pre-set samples were implanted and PBM treatment (low-level laser therapy) started (808 nm, 100 mW, 30 J/cm2). After 2 and 6 weeks, animals were euthanized, and the samples were retrieved for the histopathological, histomorphometric, picrosirius red staining and immunohistochemistry analysis. At 2 weeks post-surgery, it was observed granulation tissue and areas of newly formed bone in all experimental groups. At 6 weeks post-surgery, BG/PLGA (with or without PBM) more mature tissue around the biomaterial particles. Furthermore, there was a higher deposition of collagen for BG/PLGA in comparison with BG/PLGA/PBM, at second time-point. Histomorphometric analysis demonstrated higher values of BM.V/TV for BG compared to BG/PLGA (2 weeks post-surgery) and N.Ob/T.Ar for BG/PLGA compared to BG and BG/PBM (6 weeks post-surgery). This current study concluded that the use of BG/PLGA composites, associated or not to PBM, is a promising strategy for bone tissue engineering.
Assuntos
Substitutos Ósseos/uso terapêutico , Cerâmica/uso terapêutico , Fraturas Ósseas/terapia , Luz , Ácido Poliglicólico/uso terapêutico , Crânio/lesões , Cicatrização/efeitos dos fármacos , Animais , Substitutos Ósseos/química , Substitutos Ósseos/efeitos da radiação , Transplante Ósseo/métodos , Cimentação/métodos , Cerâmica/química , Terapia Combinada , Masculino , Teste de Materiais , Osteogênese/efeitos dos fármacos , Osteogênese/efeitos da radiação , Fototerapia/métodos , Ácido Poliglicólico/química , Ratos , Ratos Wistar , Crânio/efeitos dos fármacos , Crânio/efeitos da radiação , Engenharia TecidualRESUMO
This study aimed to optimize Cymbopogon citratus essential oil loaded into PLGA-nanoparticles by investigating the effect of processing variables (sonication time, ultrasound power, and essential oil/polymer ratio) on encapsulation efficiency and particle mean hydrodynamic diameter using Box-Behnken design. Nanoparticles were prepared by an emulsification/solvent diffusion method and physicochemically characterized by FTIR, DSC and TGA/DTA. Cytotoxicity was evaluated in human HaCat keratinocytes by WST-1 and LDH assays. The optimized formulation had a hydrodynamic mean diameter of 277â¯nm, a polydispersity index of 0.18, a Zeta potential of -16â¯mV and an encapsulation efficiency of 73%. Nanoparticle characterization showed that only citral was incorporated in nanocarriers, with some amount adsorbed on their surface, and highlighted the potential in increasing the oil thermal stability. The drug release profile demonstrated a biphasic pattern with a substantial sustained release depending on diffusion from the polymeric matrix. Toxicity effects on cell viability of pure essential oil at low concentrations were significantly eliminated when encapsulated. Results revealed the ability of PLGA-nanoparticles to improve essential oil physicochemical characteristics, by controlling release and reducing toxicity, suggesting their potential use in pharmaceutical preparations.