RESUMEN
Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer.
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Antineoplásicos , Lípidos , Nanopartículas , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Humanos , Nanopartículas/química , Femenino , Lípidos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/química , Portadores de Fármacos/química , Animales , Sistemas de Liberación de Medicamentos , Nanomedicina/métodos , LiposomasRESUMEN
Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box-Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (-31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400-300 cm-1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.
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Alcoholes Grasos , Liposomas , Liposomas/química , Alcoholes Grasos/química , Tamaño de la Partícula , Espectroscopía Infrarroja por Transformada de Fourier , Nanopartículas/química , Portadores de Fármacos/química , Solubilidad , Composición de Medicamentos/métodos , Colesterol/química , Tensoactivos/químicaRESUMEN
In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations.
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Sulfatos de Condroitina , Nanopartículas , Sulfatos de Condroitina/química , Animales , Porcinos , Nanopartículas/química , Regeneración/efectos de los fármacos , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Supervivencia Celular/efectos de los fármacos , Humanos , Administración Tópica , Nanoestructuras/química , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
UV radiation causes long- and short-term skin damage, such as erythema and skin cancer. Therefore, the use of sunscreens is extremely important. However, concerns about UV filter safety have prompted exploration into alternative solutions, with nanotechnology emerging as a promising avenue. This systematic review identified 23 experimental studies utilizing nanocarriers to encapsulate sunscreens with the aim of enhancing their efficacy and safety. Polymeric and lipid nanoparticles are frequently employed to encapsulate both organic and inorganic UV filters along with natural antioxidants. Nanocarriers have demonstrated benefits including reduced active ingredient usage, increased sun protection factor, and mitigated photoinstability. Notably, they also decreased the skin absorption of UV filters. In summary, nanocarriers represent a viable strategy for improving sunscreen formulations, offering enhanced physicochemical properties and bolstered photoprotective effects, thereby addressing concerns regarding UV filter safety and efficacy in cosmetic applications.
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Nanopartículas , Nanotecnología , Protectores Solares , Rayos Ultravioleta , Animales , Humanos , Antioxidantes/administración & dosificación , Antioxidantes/química , Antioxidantes/farmacología , Portadores de Fármacos/química , Lípidos/química , Nanopartículas/química , Nanotecnología/métodos , Polímeros/química , Piel/metabolismo , Piel/efectos de los fármacos , Absorción Cutánea/efectos de los fármacos , Factor de Protección Solar , Protectores Solares/química , Protectores Solares/administración & dosificación , Rayos Ultravioleta/efectos adversosRESUMEN
This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190-310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors.
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Quitosano , Curcumina , Mucosa Bucal , Neoplasias de la Boca , Curcumina/química , Curcumina/farmacología , Curcumina/administración & dosificación , Quitosano/química , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Humanos , Línea Celular Tumoral , Mucosa Bucal/metabolismo , Mucosa Bucal/efectos de los fármacos , Animales , Administración Tópica , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Portadores de Fármacos/química , AdhesividadRESUMEN
BACKGROUND: Implementing encapsulation techniques is pivotal in safeguarding bioactive molecules against environmental conditions for drug delivery systems. Moreover, the food-grade nanocarrier is a delivery system and food ingredient crucial in creating nutraceutical foods. Nano α-lactalbumin has been shown to be a promissory nanocarrier for hydrophobic molecules. Furthermore, the nanoprotein can enhance the tecno-functional properties of food such as foam and emulsion. The present study investigated the nanostructured α-lactalbumin protein (nano α-la) as a delivery and controlled release system for bioactive molecules in a gastric-intestinal in vitro mimic system. RESULTS: The nano α-la was synthesized by a low self-assembly technique, changing the solution ionic strength by NaCl and obtaining nano α-la 191.10 ± 21.33 nm and a spherical shape. The nano α-la showed higher encapsulation efficiency and loading capacity for quercetin than riboflavin, a potential carrier for hydrophobic compounds. Thermal analysis of nano α-la resulted in a ΔH of -1480 J g-1 for denaturation at 57.44 °C. The nanostructure formed by self-assembly modifies the foam volume increment and stability. Also, differences between nano and native proteins in emulsion activity and stability were noticed. The release profile in vitro showed that the nano α-la could not hold the molecules in gastric fluid. The Weibull and Korsmeyer-Peppas model better fits the release profile behavior in the studied fluids. CONCLUSION: The present study shows the possibility of nano α-la as an alternative to molecule delivery systems and nutraceutical foods' formulation because of the high capacity to encapsulate hydrophobic molecules and the improvement of techno-functional properties. However, the nanocarrier is not perfectly suitable for the sustainable delivery of molecules in the gastrointestinal fluid, demanding improvements in the nanocarrier. © 2024 Society of Chemical Industry.
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Preparaciones de Acción Retardada , Lactalbúmina , Nanoestructuras , Lactalbúmina/química , Preparaciones de Acción Retardada/química , Nanoestructuras/química , Portadores de Fármacos/química , Interacciones Hidrofóbicas e Hidrofílicas , Tracto Gastrointestinal/metabolismo , Composición de Medicamentos , Quercetina/química , Humanos , Riboflavina/química , Modelos Biológicos , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Emulsiones/química , Tamaño de la PartículaRESUMEN
Cancer affects millions of people worldwide, causing death and serious health problems. Despite significant investment in the development of new anticancer compounds, there are still several limitations that can still be found. Many compounds exhibit high levels of toxicity and low bioavailability. Therefore, it is urgent to design safer, more effective, and particularly more selective compounds for oncological treatment. Dendrimers are polymeric structures that have been shown to be potential drug nanocarriers to overcome physicochemical, pharmacokinetic, and indirect pharmacodynamic issues. Due to their versatility, they can be used in the design of nanovaccines, lipophilic complexes, amphiphilic complexes, smart nanocomplexes, and others. This work targets the use of dendrimers in oncological treatment and their importance and effectiveness as drug delivery systems for the development of new therapies. For this review, only publications from the last two years are considered in this review.
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Antineoplásicos , Dendrímeros , Sistemas de Liberación de Medicamentos , Neoplasias , Dendrímeros/química , Dendrímeros/administración & dosificación , Humanos , Neoplasias/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/farmacocinética , Sistemas de Liberación de Medicamentos/métodos , Animales , Portadores de Fármacos/química , NanopartículasRESUMEN
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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Ácido Gálico , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Quercetina , Quercetina/química , Nanopartículas/química , Ácido Gálico/química , Cinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Lecitinas/química , Gelatina/química , Ácido Láctico/química , Ácido Poliglicólico/química , Liberación de Fármacos , Lípidos/química , Portadores de Fármacos/química , Tamaño de la PartículaRESUMEN
Safety and effectiveness are the cornerstone objectives of nanomedicine in developing nanotherapies. It is crucial to understand the biological interactions between nanoparticles and immune cells. This study focuses on the manufacture by the microfluidic technique of N-trimethyl chitosan/protein nanocarriers and their interaction with J774 cells to elucidate the cellular processes involved in absorption and their impact on the immune system, mainly through endocytosis, activation of lysosomes and intracellular degradation. TEM of the manufactured nanoparticles showed spherical morphology with an average diameter ranging from 36 ± 16 nm to 179 ± 92 nm, depending on the concentration of the cargo protein (0, 12, 55 µg/mL). FTIR showed the crosslinking between N-trimethyl chitosan and the sodium tripolyphosphate and the α-helix binding loss of BSA. TGA revealed an increase in the thermal stability of N-trimethyl chitosan/protein nanoparticles compared with the powder. The encapsulation of the cargo protein used was demonstrated using XPS. Their potential to improve cell permeability and use as nanocarriers in future vaccine formulations was demonstrated. The toxicity of the nanoparticles in HaCaT and J774 cells was studied, as well as the importance of evaluating the differentiation status of J774 cells. Thus, possible endocytosis pathways and their impact on the immune response were discussed. This allowed us to conclude that N-trimethyl chitosan nanoparticles show potential as carriers for the immune system. Still, more studies are required to understand their effectiveness and possible use in therapies.
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Quitosano , Endocitosis , Lisosomas , Nanopartículas , Quitosano/química , Lisosomas/metabolismo , Endocitosis/efectos de los fármacos , Nanopartículas/química , Animales , Ratones , Línea Celular , Humanos , Portadores de Fármacos/química , Tamaño de la Partícula , Albúmina Sérica Bovina/química , Supervivencia Celular/efectos de los fármacosRESUMEN
Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model.Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy.Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals.Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival.
[Box: see text].
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Doxorrubicina , Nanopartículas , Doxorrubicina/administración & dosificación , Animales , Femenino , Nanopartículas/química , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Ratones , Lípidos/química , Línea Celular Tumoral , Portadores de Fármacos/química , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , LiposomasRESUMEN
The incidence of breast cancer has been increasing over the last four decades, although the mortality rate has decreased. Endocrine therapy and chemotherapy are the most used options for cancer treatment but several obstacles are still attributed to these therapies. Smart materials, such as nanocarriers for targeting, delivery and release of active ingredients, sensitive to intrinsic-stimuli (pH-responsive, redox-responsive, enzyme- responsive, and thermo-responsive) and extrinsic-stimuli (ultrasound-responsive, magnetic-responsive, light-responsive) have been studied as a novel strategy in breast cancer therapy. Cyclodextrins (CDs) are used in the design of these stimuli-responsive drug carrier and delivery systems, either through inclusion complexes with hydrophobic molecules or covalent bonds with large structures to generate new materials. The present work aims to gather and integrate recent data from in vitro and in vivo preclinical studies of CD-based stimuli- responsive systems to contribute to the research in treating breast cancer. All drug carriers showed high in vitro release rates in the presence of a stimulus. The stimuli-responsive nanoplatforms presented biocompatibility and satisfactory results of IC50, inhibition of cell viability and antitumor activity against several breast cancer cell lines. Additionally, these systems led to a significant reduction in drug dosages, which encouraged possible clinical studies for better alternatives to traditional antitumor therapies.
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Antineoplásicos , Neoplasias de la Mama , Ciclodextrinas , Sistemas de Liberación de Medicamentos , Ciclodextrinas/química , Ciclodextrinas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Femenino , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
BACKGROUND: Folic acid (FA), a synthetically produced compound analogous to vitamin B9, also referred to as vitamin folate, is an essential compound in human health and faces challenges in stability during food processing. This study explores the incorporation of FA into carboxymethylcellulose (CMC) nanofibers using electrospinning to enhance its stability. RESULTS: In this study, optimization of both electrospinning and solution parameters facilitated the fabrication of nanofibers. Furthermore, incorporating FA into CMC/polyethylene oxide (PEO) nanofibers resulted in thinner fibers, with an average diameter of 88 nm, characterized by a flat shape and smooth surface. Fourier transform infrared spectroscopic analysis demonstrated substantial hydrogen bonding interactions between FA and the polar groups present in CMC. This interaction contributed to an encapsulation efficiency of 94.5%, with a yield exceeding 87%. Thermal analysis highlighted mutual interference between CMC and PEO, with FA enhancing the thermal stability and reducing the melting temperatures and enthalpies of PEO, while also increasing the reaction heats of CMC. The encapsulated FA remained stable in acidic conditions, with only 6% degradation over 30 days, demonstrating the efficacy of CMC/PEO nanofibers in safeguarding FA against acidic environments. Moreover, the nanofibers provided a protective barrier against UV radiation, thereby preserving the stability of FA. CONCLUSION: This study emphasizes the efficacy of CMC/PEO nanofibers as a protective matrix against FA degradation. The findings indicate that this innovative approach could significantly diversify the applications of FA in food fortification, addressing concerns regarding its vulnerability to temperature and hydrolysis reactions during food processing. © 2024 Society of Chemical Industry.
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Carboximetilcelulosa de Sodio , Ácido Fólico , Nanofibras , Polietilenglicoles , Nanofibras/química , Ácido Fólico/química , Carboximetilcelulosa de Sodio/química , Polietilenglicoles/química , Estabilidad de Medicamentos , Liberación de Fármacos , Portadores de Fármacos/química , Composición de Medicamentos/métodosRESUMEN
In this study, we report the synthesis and characterization of pH-responsive nanoconjugates for targeted drug delivery. Galactomannan extracted from D. regia seeds was oxidized to form aldehyde groups, achieving a percentage of oxidation of 25.6 %. The resulting oxidized galactomannan (GMOX) was then copolymerized with PINIPAm-NH2, yielding a copolymer. The copolymer exhibited signals from both GMOX and PNIPAm-NH2 in its NMR spectrum, confirming successful copolymerization. Critical association concentration (CAC) studies revealed the formation of nanostructures, with lower CAC values observed at higher temperatures. The copolymer and GMOX reacted with doxorubicin (DOX), resulting in nanoconjugates with controlled drug release profiles, especially under acidic conditions similar to tumor microenvironments. Cytotoxicity assays demonstrated significant efficacy of the nanoconjugates against melanoma cells with reduced toxicity towards healthy cells. These findings underscore the potential of the pH-responsive nanoconjugates as promising candidates for targeted cancer therapy, offering improved therapeutic efficacy and reduced systemic side effects.
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Doxorrubicina , Galactosa , Mananos , Nanoconjugados , Doxorrubicina/farmacología , Doxorrubicina/química , Mananos/química , Mananos/farmacología , Galactosa/química , Galactosa/análogos & derivados , Humanos , Nanoconjugados/química , Concentración de Iones de Hidrógeno , Liberación de Fármacos , Línea Celular Tumoral , Portadores de Fármacos/química , Supervivencia Celular/efectos de los fármacos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antineoplásicos/química , Antineoplásicos/farmacologíaRESUMEN
In this work, a polyhedral silsesquioxane (POSS) was used as an engineered drug delivery system for two oxindolimine-copper(II) anticancer complexes, [Cu(isaepy)]+ and [Cu(isapn)]+. The interest in hybrid POSS comes from the necessity of developing materials that can act as adjuvants to improve the cytotoxicity of non-soluble metallodrugs. Functionalization of POSS with a triazole ligand (POSS-atzac) permitted the anchorage of such copper complexes, producing hybrid materials with efficient cytotoxic effects. Structural and morphological characterizations of these copper-POSS systems were performed by using different techniques (IR, NMR, thermogravimetric analysis). A combination of continuous-wave (CW) and pulsed EPR (HYSCORE) spectroscopies conducted at the X-band have enabled the complete characterization of the coordination environment of the copper ion in the POSS-atzac matrix. Additionally, the cytotoxic effects of the loaded materials, [Cu(isapn)]@POSS-atzac and [Cu(isaepy)]@POSS-atzac, were assessed toward melanomas (SK-MEL), in comparison to non-tumorigenic cells (fibroblast P4). Evaluation of their nuclease activity or ability to facilitate cleavage of DNA indicated concentrations as low as 0.6 µg mL-1, while complete DNA fragmentation was observed at 25 µg mL-1. By using adequate scavengers, investigations on active intermediates responsible for their cytotoxicity were performed, both in the absence and in the presence of ascorbate as a reducing agent. Based on the observed selective cytotoxicity of these materials toward melanomas, investigations on the reactivity of these complexes and corresponding POSS-materials with melanin, a molecule that contributes to melanoma resistance to chemotherapy, were carried out. Results indicated the main role of the binuclear copper species, formed at the surface of the silica matrix, in the observed reactivity and selectivity of these copper-POSS systems.
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Antineoplásicos , Complejos de Coordinación , Cobre , Melanoma , Compuestos de Organosilicio , Cobre/química , Cobre/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Humanos , Melanoma/tratamiento farmacológico , Melanoma/patología , Compuestos de Organosilicio/química , Compuestos de Organosilicio/farmacología , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Nanostructured lipid carriers (NLC) have emerged as innovative drug delivery systems, offering distinct advantages over other lipid-based carriers, such as liposomes and solid lipid nanoparticles. Benzocaine (BZC), the oldest topical local anesthetic in use, undergoes metabolism by pseudocholinesterase, leading to the formation of p-aminobenzoic acid, a causative agent for allergic reactions associated with prolonged BZC usage. In order to mitigate adverse effects and enhance bioavailability, BZC was encapsulated within NLC. Utilizing a 23 factorial design, formulations comprising cetyl palmitate (solid lipid), propylene glycol monocaprylate (liquid lipid), and Pluronic F68 as surfactants were systematically prepared, with variations in the solid/liquid lipid mass ratios (60:40-80:20%), total lipid contents (15-25%), and BZC concentrations (1-3%). The optimized formulation underwent characterization by dynamic light scattering, differential scanning calorimetry, Raman imaging, X-ray diffraction, small-angle neutron scattering, nanotracking analysis, and transmission electron microscopy (TEM)/cryo-TEM, providing insights into the nanoparticle structure and the incorporation of BZC into its lipid matrix. NLCBZC exhibited a noteworthy encapsulation efficiency (%EE = 96%) and a 1 year stability when stored at 25 °C. In vitro kinetic studies and in vivo antinociceptive tests conducted in mice revealed that NLCBZC effectively sustained drug release for over 20 h and prolonged the anesthetic effect of BZC for up to 18 h. We therefore propose the use of NLCBZC to diminish the effective anesthetic concentration of benzocaine (from 20 to 3% or less), thus minimizing allergic reactions that follow the topical administration of this anesthetic and, potentially, paving the way for new routes of BZC administration in pain management.
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Anestésicos Locales , Benzocaína , Portadores de Fármacos , Lípidos , Benzocaína/administración & dosificación , Benzocaína/química , Anestésicos Locales/administración & dosificación , Anestésicos Locales/química , Anestésicos Locales/farmacocinética , Anestésicos Locales/farmacología , Portadores de Fármacos/química , Animales , Lípidos/química , Ratones , Nanoestructuras/química , Liberación de Fármacos , Masculino , Nanopartículas/químicaRESUMEN
Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200â¯nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35-40â¯mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 µm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.
Asunto(s)
Lípidos , Melanoma , Nanopartículas , Polímeros , Humanos , Nanopartículas/química , Lípidos/química , Melanoma/tratamiento farmacológico , Melanoma/patología , Polímeros/química , Polímeros/farmacología , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/química , Tamaño de la Partícula , Alcaloides/química , Alcaloides/farmacología , Línea Celular Tumoral , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Antineoplásicos/farmacología , Antineoplásicos/química , Administración Tópica , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Propiedades de SuperficieRESUMEN
Solasonine (SS) and solamargine (SM) are alkaloids known for their antioxidant and anticancer properties, which can be further enhanced by encapsulating them in nanoparticles. This led to a study on the potential therapeutic benefits of SS and SM against bladder cancer when encapsulated in lipid-polymer hybrid nanoparticles (LPHNP). The LPHNP loaded with SS/SM were prepared using the emulsion and sonication method and their physical-chemical properties characterized. The biological effects of these nanoparticles were then tested in both 2D and 3D bladder cancer cell culture models, as well as in a syngeneic orthotopic mouse model based on the MB49 cell line and ethanol epithelial injury. The LPHNP-SS/SM had an average size of 130 nm, a polydispersity index of 0.22 and a positive zeta potential, indicating the presence of chitosan coating on the nanoparticle surface. The dispersion of LPHNP-SS/SM was found to be monodispersed with a span index of 0.539, as measured by nanoparticle tracking analysis (NTA). The recrystallization index, calculated from DSC data, was higher for the LPHNP-SS/SM compared to LPHNPs alone, confirming the presence of alkaloids within the lipid matrix. The encapsulation efficiency (EE%) was also high, with 91.08 % for SS and 88.35 % for SM. Morphological analysis by AFM and Cryo-TEM revealed that the nanoparticles had a spherical shape and core-shell structure. The study showed that the LPHNP-SS/SM exhibited mucoadhesive properties by physically interacting with mucin, suggesting a potential improvement in interaction with mucous membrane. Both the free and nanoencapsulated SS/SM demonstrated dose-dependent cytotoxicity against bladder cancer cell lines after 24 and 72 h of treatment. In 3D bladder cell culture, the nanoencapsulated SS/SM showed an IC50 two-fold lower than free SS/SM. In vivo studies, the LPHNP-SS/SM displayed an antitumoral effect at high doses, leading to a significant reduction in bladder volume compared to the positive control. However, there were observed instances of systemic toxicity and liver damage, indicated by elevated levels of transaminases (TGO and TGP). Overall, these results indicate that the LPHNPs effectively encapsulated SS/SM, showing high encapsulation efficiency and stability, along with promising in vitro and in vivo antitumoral effects against bladder cancer. Further evaluation of its systemic toxicity effects is necessary to ensure its safety and efficacy for potential clinical application.
Asunto(s)
Lípidos , Nanopartículas , Alcaloides Solanáceos , Neoplasias de la Vejiga Urinaria , Animales , Nanopartículas/química , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Línea Celular Tumoral , Lípidos/química , Alcaloides Solanáceos/administración & dosificación , Alcaloides Solanáceos/química , Alcaloides Solanáceos/farmacología , Polímeros/química , Ratones , Humanos , Femenino , Portadores de Fármacos/química , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Tamaño de la Partícula , Supervivencia Celular/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
The success of obtaining solid dispersions for solubility improvement invariably depends on the miscibility of the drug and polymeric carriers. This study aimed to categorize and select polymeric carriers via the classical group contribution method using the multivariate analysis of the calculated solubility parameter of RX-HCl. The total, partial, and derivate parameters for RX-HCl were calculated. The data were compared with the results of excipients (N = 36), and a hierarchical clustering analysis was further performed. Solid dispersions of selected polymers in different drug loads were produced using solvent casting and characterized via X-ray diffraction, infrared spectroscopy and scanning electron microscopy. RX-HCl presented a Hansen solubility parameter (HSP) of 23.52 MPa1/2. The exploratory analysis of HSP and relative energy difference (RED) elicited a classification for miscible (n = 11), partially miscible (n = 15), and immiscible (n = 10) combinations. The experimental validation followed by a principal component regression exhibited a significant correlation between the crystallinity reduction and calculated parameters, whereas the spectroscopic evaluation highlighted the hydrogen-bonding contribution towards amorphization. The systematic approach presented a high discrimination ability, contributing to optimal excipient selection for the obtention of solid solutions of RX-HCl.
Asunto(s)
Química Farmacéutica , Excipientes , Polímeros , Clorhidrato de Raloxifeno , Solubilidad , Difracción de Rayos X , Polímeros/química , Excipientes/química , Clorhidrato de Raloxifeno/química , Análisis Multivariante , Difracción de Rayos X/métodos , Química Farmacéutica/métodos , Portadores de Fármacos/química , Composición de Medicamentos/métodos , Microscopía Electrónica de Rastreo/métodos , Enlace de Hidrógeno , Cristalización/métodosRESUMEN
Aim: To investigate the effect of surfactant type on curcumin-loaded (CUR) PLGA nanoparticles (NPs) to modulate monocyte functions. Materials & methods: The nanoprecipitation method was used, and PLGA NPs were designed using Pluronic F127 (F127) and/or lecithin (LEC) as surfactants. Results: The Z-average of the NPs was <200 nm, they had a spherical shape, Derjaguin-Muller-Toporov modulus >0.128 MPa, they were stable during storage at 4°C, ζ-potential â¼-40 mV, polydispersity index <0.26 and % EE of CUR >94%. PLGA-LEC/F127 NPs showed favorable physicochemical and nanomechanical properties. These NPs were bound and internalized mainly by monocytes, suppressed monocyte-induced reactive oxygen species production, and decreased the ability of monocytes to modulate T-cell proliferation. Conclusion: These results demonstrate the potential of these NPs for targeted therapy.
This study explores how different surfactants affect curcumin-loaded PLGA nanoparticles, a biodegradable polymer. The nanoparticles were designed using Pluronic F127 and/or lecithin as surfactants. They are less than 200 nm and spherical. They are stable when stored at 4 °C, with a surface charge of about -40 mV, and can encapsulate more than 94% of curcumin.The results of this study are promising, showing that PLGA nanoparticles using a mixture of lecithin and Pluronic F127 as surfactants have favorable properties toward monocyte adhesion. They are primarily taken up by monocytes, a type of white blood cell, and demonstrate a remarkable ability to reduce the production of reactive oxygen species, which can cause cell damage, as well as the ability of monocytes to stimulate the proliferation of T cells. This underscores the potential of these nanoparticles in targeted therapy, particularly in diseases where monocytes play a pivotal role, such as chronic inflammatory conditions.