RESUMO
We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.
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Rivastigmine is an acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibitor drug approved by the US Food and Drug Administration (FDA) for the treatment of mild to moderate dementia of Alzheimer's type. However, its first-pass metabolism and gastrointestinal side effects negatively affect the tolerability and efficacy of oral therapy. These adverse effects could be avoided with the use of a sustained -release formulation as an intramuscular (IM) administration system. The objective of this work was to develop polylactic co-glycolic acid (PLGA) microparticles for the sustained release of rivastigmine and to evaluate its stability during storage, tissue tolerance, in vitro release, and in vivo pharmacokinetics after its IM administration. The microparticles were made by the solvent evaporation emulsion method. A series of formulation parameters (the type of polymer used, the amount of polymer used, the initial amount of rivastigmine, and the volume of PVA 0.1% w/v) were studied to achieve an encapsulation efficiency (EE) and a rivastigmine load of 54.8 ± 0.9% and 3.3 ± 0.1%, respectively. The microparticles, whose size was 56.1 ± 2.8 µm, had a spherical shape and a smooth surface. FT-IR analysis showed that there is no chemical interaction between rivastigmine and the polymer. PLGA microparticles maintain rivastigmine retained and stable under normal (5 ± 3 °C) and accelerated storage (25 ± 2 °C and 60 ± 5 % RH) conditions for at least 6 months. The microparticles behaved as a sustained release system both in vitro and in vivo compared to non-encapsulated rivastigmine. The IM administration of the formulation in rats did not produce significant tissue damage. However, it is necessary to reproduce the experiments with multiple doses to rule out a negative effect in terms of tolerability in chronic treatment. To the best of our knowledge, this study is the only one that has obtained the sustained release of rivastigmine from PLGA microparticles after IM administration in an in vivo model.
Assuntos
Acetilcolinesterase , Glicóis , Ratos , Animais , Preparações de Ação Retardada , Rivastigmina , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Espectroscopia de Infravermelho com Transformada de Fourier , Butirilcolinesterase , Polímeros , Tamanho da Partícula , MicroesferasRESUMO
The objective of this study was to develop a novel subgingival sustained-release system for local delivery of bioactive minocycline hydrochloride for periodontal disease treatment in dogs. The system incorporated the Minocycline hydrochloride-Calcium-Dextran sulfate sodium into a thermoresponsive Pluronic F127 hydrogel. Minocycline hydrochloride was sustained release from the system for up to 10 days and the release kinetics fit the power law model. The release medium had a significant statistical difference in antimicrobial activity to Aggregatibacter actinomycetemcomitans. The results showed the system was a promising subgingival sustained-release minocycline hydrochloride delivery system for periodontal disease treatment in dogs.
O objetivo deste estudo foi desenvolver um novo sistema subgengival de liberação sustentada para administração local de cloridrato bioativo de minociclina para tratamento da doença periodontal em cães. O sistema incorporou o cloridrato de minociclina-cálcio-dextrano sulfato de sódio em um hidrogel Pluronic F127 termorresponsivo. O cloridrato de minociclina foi liberado do sistema por até 10 dias e a cinética de liberação se ajustou ao modelo da lei de potência. O meio de liberação apresentou uma diferença estatística significativa na atividade antimicrobiana para Aggregatibacter actinomycetemcomitans. Os resultados mostraram que o sistema foi um promissor sistema subgengival de liberação sustentada de cloridrato de minociclina para o tratamento da doença periodontal em cães.
Assuntos
Animais , Cães , Doenças Periodontais , Terapêutica , Aggregatibacter actinomycetemcomitans , HidrogéisRESUMO
The drug delivery systems are an important strategy of pharmaceutical technology to modulate undesirable properties, increasing efficacy, and reducing the side effects of active pharmaceutical ingredients (API). The sustained release is a type of controlled-release system that provides a suitable drug level in the blood through a slow release rate. An interesting alternative to achieve a controlled release is the application of carrier materials such as polymers, cyclodextrins, and clays. Sodium montmorillonite (Na-MMT) is a biocompatible natural clay that allows the insertion of organic compounds in interlamellar space, owing to its high cation exchange capacity and large internal surface area. Bromopride (BPD) is an aminated compound with antiemetic properties classified as class II (low solubility, high permeability) of the Biopharmaceutical Classification System (BCS). Herein, the aim of the study was the development and investigation of a drug delivery system formed by intercalation of BPD with Na-MMT. The results indicate the successful intercalation of this API with the lamellar silicate, meanwhile, there was no evidence of BPD intercalation in organic montmorillonite. The Na-MMT/BPD molecular complex exhibits a sustained release in performed assays. Molecular dynamics simulations suggested that BPD molecules interact with the montmorillonite layer through ion-dipole interactions and also between BPD molecules, forming hydrogen bonds web into montmorillonite interlayer space. The new drug delivery system showed an alternative to achieve the BPD sustained release, which may improve its pharmacological performance in therapeutic applications.
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Bentonita , Metoclopramida , Bentonita/química , Argila , Preparações de Ação Retardada , Metoclopramida/análogos & derivadosRESUMO
Gold nanoparticles (AuNPs) have shown interesting properties and specific biofunctions, providing benefits and new opportunities for controlled release systems. In this research, we demonstrated the use of natural rubber latex (NRL) from Hevea brasiliensis as a carrier of AuNPs and the antibiotic metronidazole (MET). We prepared AuNP-MET-NRL and characterized by physicochemical, biological and in vitro release assays. The effect of AuNPs on MET release was evaluated using UV-Vis and Laser-Induced Breakdown Spectroscopy (LIBS) techniques. AuNPs synthesized by Turkevich and Frens method resulted in a spherical shape with diameters of 34.8 ± 5.5 nm. We verified that there was no emergence or disappearance of new vibrational bands. Qualitatively and quantitatively, we showed that the MET crystals dispersed throughout the NRL. The Young's modulus and elongation values at dressing rupture were in the range appropriate for human skin application. 64.70% of the AuNP-MET complex was released within 100 h, exhibiting a second-order exponential release profile. The LIBS technique allowed monitoring of the AuNP release, indicating the Au emission peak reduction at 267.57 nm over time. Moreover, the dressing displayed an excellent hemocompatibility and fibroblast cell viability. These results demonstrated that the AuNP-MET-NRL wound dressing is a promising approach for dermal applications.
Assuntos
Ouro , Látex , Nanopartículas Metálicas , Metronidazol , Bandagens , Ouro/química , Humanos , Látex/química , Nanopartículas Metálicas/química , Metronidazol/farmacologia , Borracha/químicaRESUMO
Abstract Sustained release matrix tablets of 100 mg losartan potassium HCl were fabricated with two release retarding polymers namely HPMC K100 M and affinisol by direct compression method. Nine trial formulations were prepared by varying content of these polymers, each from 50 mg to 100 mg; keeping the total weight of the tablet 310 mg. The best formulation was selected based on in vitro drug release profile for 12 hours conducted in Type II dissolution apparatus at 50 rpm and water as dissolution medium. Pre-compression parameters such as bulk density, tap density, Carr's index and Hausner ratio were evaluated for the selected tablet. The tablets were subjected to thickness, weight variation test, drug content, hardness and friability. Drug release kinetics, surface morphology and accelerated stability study were investigated for that selected formulation. Formulation F4 with the composition of 75 mg HPMC K100M and 100 mg affinisol was selected as the best formulation that extended the drug release up to 12 hours. Pre-compression parameters and other tableting properties were within the Pharmacopoeia limit. Release kinetics analysis proved non-fickian zero-order drug release and that was further confirmed by surface morphology of the tablets before and after dissolution study visualized by SEM. The developed formulation was found to be stable for one month stored at 60 âC.
Assuntos
Comprimidos/análise , Técnicas In Vitro/métodos , Preparações Farmacêuticas/análise , Losartan/agonistas , Composição de Medicamentos/métodos , Dissolução , Liberação Controlada de Fármacos/efeitos dos fármacos , MétodosRESUMO
Abstract Design of experiment (DoE) is a useful time and cost-effective tool for analyzing the effect of independent variables on the formulation characteristics. The aim of this study is to evaluate the effect of the process variables on the characteristics involved in the preparation of Diclofenac Sodium (DC) loaded ethylcellulose (EC) nanoparticles (NP) using Central Composite Design (CCD). NP were prepared by W/O/W emulsion solvent evaporation method. Three factors were investigated (DC/EC mass ratio, PVA concentration, homogenization speed) in order to optimize the entrapment efficiency (EE) and the particle size of NP. The optimal formulation was characterized by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and in vitro release. Optimized formulation showed an EE of 49.09 % and an average particle size of 226.83 nm with a polydispersity index of 0.271. No drug-polymer interaction was observed in FTIR and DSC analysis. SEM images showed that the particles are spherical and uniform. The in vitro release study showed a sustained release nature, 53.98 % of the encapsulated drug has been released over 24hours period. This study demonstrated that statistical experimental design methodology can optimize the formulation and the process variables to achieve favorable responses.
Assuntos
Preparações Farmacêuticas , Diclofenaco/análise , Otimização de Processos , Nanopartículas/análise , Técnicas In Vitro/instrumentação , Varredura Diferencial de Calorimetria/instrumentação , Microscopia Eletrônica de Varredura/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Custos e Análise de Custo/métodos , Metodologia como Assunto , Análise de FourierRESUMO
A rational design accurate based on the use of Statistical Design of the Experiments (DoE) and Molecular Dynamics Simulations Studies allows the prediction and the understanding of thermo-responsive hydrogels prepared regarding their gelation temperature and anti-cancer drug release rate. N-isopropylacrilamide (NIPAM) modified with specific co-monomers and crosslinkers, can be used to prepare "on-demand" thermo-responsive hydrogels with the ideal properties for clinical applications in which local sustained release of drugs is crucial. Two preferential formulations resulting from the predictive studies of DoE and In Silico methods were synthesized by radical polymerization, fully characterized, and loaded with the anticancer drug Doxorubicin (Dox). The hydrogel formulations were characterized by swelling rate, turbidity, FTIR, 1H NMR, SEM, gelation time, rheology, and biocompatibility assays. Both formulations demonstrated adequate morphologic, rheological, and biocompatibility properties; however, important differences in terms of drug retention were detected. As demonstrated by a Dox cumulative release study and posteriorly confirmed by an efficacy assay in an in vitro colorectal cancer model, the formulation composed by NIPAM and 4-penten-1-ol crosslinked with poly(ethylene glycol) diacrylate (PEGDA) (PNiPenPH) present a slow release over the time, presenting ideal properties to become and ideal depot system for the local sustained release of anticancer drugs as adjuvant therapy or in the case of non-resectable tumors.
Assuntos
Antineoplásicos , Neoplasias do Colo , Antineoplásicos/farmacologia , Neoplasias do Colo/tratamento farmacológico , Preparações de Ação Retardada , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Humanos , Hidrogéis , TemperaturaRESUMO
The need of pharmacological strategies to preclude breast cancer development motivated us to develop a non-aqueous microemulsion (ME) capable of forming a depot after administration in the mammary tissue and uptake of interstitial fluids for prolonged release of the retinoid fenretinide. The selected ME was composed of phosphatidylcholine/tricaprylin/propylene glycol (45:5:50, w/w/w) and presented a droplet diameter of 175.3 ± 8.9 nm. Upon water uptake, the ME transformed successively into a lamellar phase, gel, and a lamellar phase-containing emulsion in vitro as the water content increased and released 30% of fenretinide in vitro after 9 days. Consistent with the slow release, the ME formed a depot in cell cultures and increased fenretinide IC50 values by 68.3- and 13.2-fold in MCF-7 and T-47D cells compared to a solution, respectively. At non-cytotoxic concentrations, the ME reduced T-47D cell migration by 75.9% and spheroid growth, resulting in â¼30% smaller structures. The depot formed in vivo prolonged a fluorochrome release for 30 days without producing any sings of local irritation. In a preclinical model of chemically induced carcinogenesis, ME administration every 3 weeks for 3 months significantly reduced (4.7-fold) the incidence of breast tumors and increased type II collagen expression, which might contribute to limit spreading. These promising results support the potential ME applicability as a preventive therapy of breast cancer.
Assuntos
Anticarcinógenos/administração & dosagem , Neoplasias da Mama/prevenção & controle , Fenretinida/administração & dosagem , Neoplasias Mamárias Experimentais/prevenção & controle , Animais , Anticarcinógenos/farmacocinética , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Emulsões , Feminino , Fenretinida/farmacocinética , Humanos , Concentração Inibidora 50 , Células MCF-7 , Glândulas Mamárias Animais/efeitos dos fármacos , Glândulas Mamárias Animais/patologia , Neoplasias Mamárias Experimentais/induzido quimicamente , Neoplasias Mamárias Experimentais/patologia , Metilnitrosoureia/administração & dosagem , Metilnitrosoureia/toxicidade , Camundongos , RatosRESUMO
Biodegradable polymeric nanofibers containing mometasone furoate can be a new approach to drug delivery to treat chronic rhinosinusitis, providing controlled steroid delivery to the sinonasal mucosa. This study aimed to develop biodegradable polymeric nanofibers and explore the safety of these fibers in an in vivo rabbit model. The nanofibers' development has been optimized using the Response Surface Methodology (RSM) obtained with Design of Experiments (DoE) with the best conditions related to the polymer concentration and proportion of solvents used in the electrospinning process. The nanofibers were prepared, operating as a determinant factor, the nanofiber formation and its diameter evaluated by Scanning Electron Microscopy (SEM). The ideal system obtained was assessed by SEM, thermogravimetric analysis (TGA), X-ray diffraction (XRD), differential scanning calorimetry (DSC), assay, and drug delivery by UHLPC validated method. The results showed that the drug is dispersed in the polymeric matrix, is stable, and showed sustained release kinetics in a bio-relevant nasal environment (Higuchi model kinetics). In vivo tests, the level of inflammation at the animals' mucosa which received the nanofiber with the mometasone furoate was lower than those that received the nanofibers without the drug (α = 0.05). Histopathology analysis showed that the polymeric nanofibers containing mometasone are safe when topically applied on the sinonasal mucosa, opening a new horizon in chronic rhinosinusitis treatment.
Assuntos
Nanofibras , Animais , Varredura Diferencial de Calorimetria , Microscopia Eletrônica de Varredura , Polímeros , Coelhos , Difração de Raios XRESUMO
The incorporation of drugs and bioactive compounds in the natural rubber latex (NRL) matrix has been an alternative for the development of transdermal release membranes. Ibuprofen (IBF) is known to be used to treat inflammatory diseases, but when administered orally, high concentrations can cause some adverse problems. In this work, the incorporation of IBF in the NRL membranes was evaluated by physical-chemical, in vitro permeation, hemocompatibility and molecular modeling assays. In addition, the in vitro release profile of IBF in acid and basic media was analyzed during 96 h. The IBF-NRL membrane exhibited the absence of intermolecular bonding that could hinder drug release and presented compatible mechanical properties for applications as a cutaneous adhesive (0.58 and 1.12 MPa to Young's modulus and rupture tension, respectively). The IBF-NRL system did not present a significant hemolysis degree (1.67%) within 24 h. The release test indicated that in the first hours of the study, 48.5% IBF was released at basic pH and 22.5% at acidic pH, which is characteristic of a burst effect. Then, a stable release profile was observed until the end of the assay, with total IBF release of 60% in alkaline medium and 50% in acidic medium. The drug permeation results indicated that the IBF-NRL membranes can be used for the local skin treatment with permeation of 3.11% of IBF. Dynamic Molecular simulations indicated a pronounced electric dipole in the ionized form of IBF, which suggests a more effective interaction with water, explaining the efficient drug release in alkaline solutions. In general, the results demonstrate that the IBF-NRL membrane has great potential for a new adhesive that can be used for the treatment of inflammatory processes and injuries.
Assuntos
Ibuprofeno , Borracha , Liberação Controlada de FármacosRESUMO
INTRODUCTION: The most common treatment for Primary Open-Angle Glaucoma (POAG) is the daily use of eye drops. Sustained-release drug delivery systems have been developed to improve patient adherence by achieving prolonged therapeutic drug concentrations in ocular target tissues while limiting systemic exposure. The purpose of this study is to compare the efficacy and safety of bimatoprost inserts with bimatoprost eye drops in patients with POAG and Ocular Hypertension (OH). METHODS: We include OH and POAG patients aged between 40 and 75 years-old. Both OH and POAG patients had intraocular pressure (IOP) greater than 21 and ≤30 mmHg at 9:00 am without glaucoma medication and normal biomicroscopy. Five normal patients with IOP≤14 mmHg constitute the control group. A chitosan-based insert of bimatoprost was placed at the upper conjunctival fornix of the right eye. In the left eye, patients used one drop of LumiganTM daily at 10:00 pm. For statistical analysis, a two-way analysis of variance (ANOVA), Student t-test, and paired t-test is used. RESULTS: Sixteen POAG and 13 OH patients with a mean age of 61 years were assessed. In both eyes, IOP reduction was similar during three weeks of follow-up (19.5±2.2 mmHg and 16.9±3.1 mmHg), insert, and eye drop, respectively; P=0.165). The percentage of IOP reduction in the third week was 30% for insert and 35% for eye drops (P=0.165). No intolerance or discomfort with the insert was reported. Among the research participants, 58% preferred the use of the insert while 25% preferred eye drops, and 17% reported no preference. CONCLUSION: Bimatoprost-loaded inserts showed similar efficacy to daily bimatoprost eye drops during three weeks of follow up, without major side effects. This might suggest a possible change in the daily therapeutic regimen for the treatment of POAG and OH.
Assuntos
Glaucoma de Ângulo Aberto , Glaucoma , Hipertensão Ocular , Adulto , Idoso , Amidas , Anti-Hipertensivos , Bimatoprost , Glaucoma de Ângulo Aberto/tratamento farmacológico , Humanos , Pressão Intraocular , Pessoa de Meia-Idade , Hipertensão Ocular/tratamento farmacológico , Soluções OftálmicasRESUMO
Intragenic antimicrobial peptides (IAPs) are internal sequences of proteins with physicochemical similarities to Antimicrobial Peptides (AMPs) that, once identified and synthesized as individual entities, present antimicrobial activity. Many mature proteins encoded by the genomes of virtually any organism may be regarded as inner reservoirs of IAPs, conferring them ample biotechnological potential. However, IAPs may also share shortcomings with AMPs, such as low half-life in biological media and non-specific adsorption in eukaryotic cells. The present manuscript reports a translational approach that encompasses the uncovering of two novel IAPs from human proteins as well as the first results concerning the incorporation and sustained release of one of these peptides from ureasil-polyether hybrid polymeric films. For such, the software Kamal was used to scan putative IAPs in the human proteome, and two peptides, named Hs05 and Hs06, were identified, synthesized, and tested as antimicrobials. Biophysical assays were conducted using model phospholipid vesicles and 1H NMR solution structures in phospholipid micelles were obtained for the IAP Hs05. This peptide was incorporated in a polymeric matrix composed of the ureasil/PPO-PEO-PPO triblock copolymer, and the resulting films were evaluated by atomic force microscopy and imaging mass spectrometry. The release rate of Hs05 from the polymeric matrix was assessed and the antimicrobial activity of Hs05-loaded hybrid polymeric films was evaluated against the bacterium Escherichia coli. This study represents the first steps towards the development of polymeric films enriched with IAPs obtained from the human proteome as sustained release devices for topical application.
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Anti-Infecciosos , Micelas , Anti-Infecciosos/farmacologia , Humanos , Peptídeos , Polímeros , Proteínas Citotóxicas Formadoras de PorosRESUMO
A series of hydrogels with a specific release profile of linezolid was successfully synthesized. The hydrogels were synthesized by cross-linking polyvinyl alcohol (PVA) and aliphatic dicarboxylic acids, which include succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The three crosslinked hydrogels were prepared by esterification and characterized by equilibrium swelling ratio, infrared spectroscopy, thermogravimetric analysis, mechanical properties, and scanning electron microscopy. The release kinetics studies of the linezolid from prepared hydrogels were investigated by cumulative drug release and quantified by chromatographic techniques. Mathematical models were carried out to understand the behavior of the linezolid release. These data revealed that the sustained release of linezolid depends on the aliphatic dicarboxylic acid chain length, their polarity, as well as the hydrogel crosslinking degree and mechanical properties. The in vitro antibacterial assay of hydrogel formulations was assessed in an Enterococcus faecium bacterial strain, showing a significant activity over time. The antibacterial results were consistent with cumulative release assays. Thus, these results demonstrated that the aliphatic dicarboxylic acids used as crosslinkers in the PVA hydrogels were a determining factor in the antibiotic release profile.
RESUMO
This paper describes a melting solidification printing process (MESO-PP) capable of obtaining printed oral solid dosage forms in a safe, versatile, and robust manner avoiding the use of solvents and high temperatures. MESO-PP and Gelucire® 50/13 (fatty polyethylene glycol esters) as ink can be used to obtain a floating sustained-release system with the aim of improving the dissolution and absorption of drugs, such as ricobendazole (RBZ), which have a low and erratic bioavailability. Gelucire 50/13 can be considered a good material to formulate inks using MESO-PP. As a model, the RBZ allowed us to assess that there were no changes in crystallinity and the API-ink interactions were ruled out using TGA, DSC, XRD and FT-IR assays. A batch of printlets, obtained using MESO-PP, fulfilled USP requirements regarding uniformity of mass (827 ± 9 mg) and drug content (211 ± 5 mg). Hardness and friability were 39.23 ± 9.65 N and 1.07 ± 0.5% respectively, just above the 1% USP tablet-friability limit. It was possible to obtain tablets of different sizes with high precision (r2 = 0.995). In vitro dissolution test showed that the printlet had a sustained-release of RBZ (only 7% after 15 min), that erosion was the predominant mechanism for drug release (n-value of Korsmeyer-Peppas equation = 0.991; r2 = 0.99) and that changes in the internal structures modify the release. Consequently, MESO-PP can be considered an excellent alternative to obtain solid pharmaceutical dosage forms with variable geometries for different pharmaceutical applications.
Assuntos
Impressão Tridimensional , Tecnologia Farmacêutica , Albendazol/análogos & derivados , Liberação Controlada de Fármacos , Solventes , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos , TemperaturaRESUMO
The data article refers to the paper "supramolecular hydrogel based on cellulose for sustained release of therapeutic substances with antimicrobial and wound healing properties"[1]. The dataset includes the synthesis and characterization of (E)-1,3-bis(4-(allyloxy)phenyl)prop2-en-1-one (3) (crosslinking agent). Moreover, the multiwall carbon nanotubes (MWCNTs) synthesis and functionalization (MWCNTs-COOH) are described. The formulation obtained by adding multiwalled carbon nanotubes-COOH with the crosslinked cellulose-chalcone hydrogel is abbreviated as MWCNTsCCH, and the same formulation loaded with therapeutic substances (TS) is named MWCNTsCCH-TS. The MWCNTsCCH database such as components and their amounts, swelling degree, thermogravimetric analysis, and cytotoxicity evaluation are depicted. Finally, to elucidate the mechanism of therapeutic substances release, the obtained averages of the release profiles were fitted through mathematical models.
RESUMO
A multifaceted hydrogel-based formulation was reported. The hydrogel was prepared by crosslinking cellulose and substituted chalcone. Moreover, the formulation was conjugated with carbon nanotubes with the aim of increasing the loading amount of bioactive compounds such as allantoin, dexpanthenol, resveratrol and linezolid. The hydrogel formation was confirmed by swelling tests, FT-IR spectroscopy, thermogravimetric analysis and SEM. The hydrogel showed an improved release rate of therapeutic substances, exhibiting a simultaneous and coordinated release according to the chromatographic studies. The efficacy of drug release was confirmed by wound closure and in vivo wound healing studies that showed promising healing results. The antibacterial assays demonstrated that the sustained release of linezolid tends to be very effective. In conclusion, a multifaceted formulation based on carbon nanotube-containing cellulose-chalcone was developed that can potentially be utilized in treating complex wounds owing to its improved wound healing properties and prevention of potential infections.
Assuntos
Antibacterianos/farmacologia , Celulose/farmacologia , Enterococcus faecium/efeitos dos fármacos , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Linhagem Celular , Celulose/química , Liberação Controlada de Fármacos , Hidrogéis/química , Cinética , Substâncias Macromoleculares/química , Substâncias Macromoleculares/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , TemperaturaRESUMO
In this study, microemulsions capable of transforming into nanostructured hexagonal phase gels in vivo upon uptake of biological fluids for naltrexone prolonged release were investigated as a strategy for management of alcohol use disorder (AUD). Microemulsions were prepared using monoolein, tricaprylin, water and propylene glycol; after preliminary characterization, one formulation was selected, which contained 55% of monoolein-tricaprylin (M-55). This microemulsion displayed size below 200 nm and Newtonian rheological behavior. Liquid crystalline gels formed in vitro upon 8 h of contact with water following a second order kinetics. After 120 h, <50% of naltrexone was released in vitro independently on drug loading (5 or 10%). In vivo, gels formed within 24 h of M-55 subcutaneous administration, and persisted locally for over 30 days providing slow release of the fluorescent marker Alexa fluor compared to a solution. Using the conditioned place preference paradigm, a test used to measure drug's rewarding effects, a single dose of M-55 containing 5% naltrexone reduced the time spent in the ethanol-paired compartment by 1.8-fold compared to saline; this effect was similar to that obtained with daily naltrexone injections, demonstrating the formulation efficacy and its ability to reduce dosing frequency. A more robust effect was observed following administration of M-55 containing 10% of naltrexone, which was compatible with aversion. These results support M-55 as a platform for sustained release of drugs that can be further explored for management of AUD to reduce dosing frequency and aid treatment adherence.
Assuntos
Dissuasores de Álcool/administração & dosagem , Alcoolismo/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Etanol/administração & dosagem , Naltrexona/administração & dosagem , Nanoestruturas/administração & dosagem , Dissuasores de Álcool/sangue , Dissuasores de Álcool/síntese química , Alcoolismo/sangue , Animais , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Injeções Subcutâneas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Naltrexona/sangue , Naltrexona/síntese química , Nanoestruturas/químicaRESUMO
Tablet splitting is a practice disseminated among health professionals for dose adjustments, swallowing facilitation or even treatment cost reduction. Nevertheless, tablets not designed for this purpose cause imprecise dosage and stability loss with important therapeutic repercussions. Novel technologies of modified drug release tablets have come to market including new materials and innovative production processes, for example, polymeric matrix, orodispersible, 3D printing, MUPs, etc. The heterogeneity and complexity of these tablets go well beyond a traditional gastroresistant coating tablet, making orientations on the practice of tablet subdivision difficult. This editorial aims to provide a critical and up-to-date evaluation of this scenario based on the most recent studies involving the subdivision of modified-release tablets.
Assuntos
Polímeros , Impressão Tridimensional , ComprimidosRESUMO
The subdivision of sustained release tablets is a controversial issue, especially concerning its impact on dissolution profiles. The purpose of this study was to elucidate the behavior upon subdivision of this class of tablets. For this, three common sustained release matrices containing different technologies were selected, e.g., a tablet comprised of a multiple-unit particulate system (MUPS), a lipid matrix tablet, and a polymeric inert matrix tablet. These tablets were studied concerning their physicochemical performance, dissolution rate, and kinetic profile before and after their subdivision. When subdivision occurred in the scoreline, mass variation and mass loss were below the mean values described in the literature. The dissolution of tablets with inert matrices and some lipid tablets that had their matrices preserved along the dissolution was influenced directly by tablet surface area, which increased after the subdivision. Such a result implies possible clinical consequences, especially in the case of drugs with a narrow therapeutic window, such as clomipramine. Conversely, the subdivision of MUPS tablets did not interfere in the dissolution profile since the drug was released from the granules that resulted from tablet disintegration. Hence, MUPS technology is the most recommended to produce sustained release matrix tablets intended for dose adjustment upon subdivision.