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1.
Int J Mol Sci ; 22(17)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34502086

RESUMO

In recent years, enzymes have risen as promising therapeutic tools for different pathologies, from metabolic deficiencies, such as fibrosis conditions, ocular pathologies or joint problems, to cancer or cardiovascular diseases. Treatments based on the catalytic activity of enzymes are able to convert a wide range of target molecules to restore the correct physiological metabolism. These treatments present several advantages compared to established therapeutic approaches thanks to their affinity and specificity properties. However, enzymes present some challenges, such as short in vivo half-life, lack of targeted action and, in particular, patient immune system reaction against the enzyme. For this reason, it is important to monitor serum immune response during treatment. This can be achieved by conventional techniques (ELISA) but also by new promising tools such as microarrays. These assays have gained popularity due to their high-throughput analysis capacity, their simplicity, and their potential to monitor the immune response of patients during enzyme therapies. In this growing field, research is still ongoing to solve current health problems such as COVID-19. Currently, promising therapeutic alternatives using the angiotensin-converting enzyme 2 (ACE2) are being studied to treat COVID-19.


Assuntos
Enzima de Conversão de Angiotensina 2/uso terapêutico , COVID-19/tratamento farmacológico , Terapia Enzimática/métodos , Proteínas Recombinantes/uso terapêutico , Enzima de Conversão de Angiotensina 2/farmacologia , Ensaios Clínicos Fase II como Assunto , Composição de Medicamentos/métodos , Estabilidade Enzimática , Terapia Enzimática/história , Terapia Enzimática/tendências , Meia-Vida , História do Século XX , História do Século XXI , Humanos , Proteínas Recombinantes/farmacologia , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacos
2.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361740

RESUMO

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.


Assuntos
Materiais Biocompatíveis/síntese química , Portadores de Fármacos/síntese química , Nanoestruturas/química , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Animais , Materiais Biocompatíveis/farmacocinética , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Peptídeos/farmacocinética , Distribuição Tecidual
3.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361743

RESUMO

While investigating the possible synergistic effect of the conventional anticancer therapies, which, taken individually, are often ineffective against critical tumors, such as central nervous system (CNS) ones, the design of a theranostic nanovector able to carry and deliver chemotherapy drugs and magnetic hyperthermic agents to the target radiosensitizers (oxygen) was pursued. Alongside the original formulation of polymeric biodegradable oxygen-loaded nanostructures, their properties were fine-tuned to optimize their ability to conjugate therapeutic doses of drugs (doxorubicin) or antitumoral natural substances (curcumin). Oxygen-loaded nanostructures (diameter = 251 ± 13 nm, ζ potential = -29 ± 5 mV) were finally decorated with superparamagnetic iron oxide nanoparticles (SPIONs, diameter = 18 ± 3 nm, ζ potential = 14 ± 4 mV), producing stable, effective and non-agglomerating magnetic nanovectors (diameter = 279 ± 17 nm, ζ potential = -18 ± 7 mV), which could potentially target the tumoral tissues under magnetic driving and are monitorable either by US or MRI imaging.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Quitosana/química , Hipertermia Induzida/métodos , Nanopartículas de Magnetita/química , Radiossensibilizantes/farmacologia , Nanomedicina Teranóstica/métodos , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Meios de Contraste/síntese química , Meios de Contraste/farmacologia , Curcumina/química , Curcumina/farmacologia , Sulfato de Dextrana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Composição de Medicamentos/métodos , Humanos , Cinética , Nanopartículas de Magnetita/ultraestrutura , Oxigênio/química , Oxigênio/farmacologia , Radiossensibilizantes/síntese química
5.
Chem Pharm Bull (Tokyo) ; 69(7): 674-680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34193716

RESUMO

Quality by design (QbD) is an essential concept for modern manufacturing processes of pharmaceutical products. Understanding the science behind manufacturing processes is crucial; however, the complexity of the manufacturing processes makes implementing QbD challenging. In this study, structural equation modeling (SEM) was applied to understand the causal relationships between variables such as process parameters, material attributes, and quality attributes. Based on SEM analysis, we identified a model composed of the above-mentioned variables and their latent factors without including observational data. Difficulties in fitting the observed data to the proposed model are often encountered in SEM analysis. To address this issue, we adopted Bayesian estimation with Markov chain Monte Carlo simulation. The tableting process involving the wet-granulation process for acetaminophen was employed as a model case for the manufacturing process. The results indicate that SEM analysis could be useful for implementing QbD for the manufacturing processes of pharmaceutical products.


Assuntos
Análise de Classes Latentes , Comprimidos/química , Acetaminofen/química , Teorema de Bayes , Composição de Medicamentos/métodos , Cadeias de Markov , Método de Monte Carlo , Análise de Componente Principal
6.
Int J Mol Sci ; 22(11)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199951

RESUMO

Skin barrier functions, environmental insults, and genetic backgrounds are intricately linked and form the basis of common inflammatory skin disorders, such as atopic dermatitis, psoriasis, and seborrheic dermatitis, which may seriously affect one's quality of life. Topical therapy is usually the first line of management. It is believed that successful topical treatment requires pharmaceutical formulation from a sufficient dosage to exert therapeutic effects by penetrating the stratum corneum and then diffusing to the target area. However, many factors can affect this process including the physicochemical properties of the active compound, the composition of the formulation base, and the limitations and conditions of the skin barrier, especially in inflammatory skin. This article briefly reviews the available data on these issues and provides opinions on strategies to develop a suitable formulation for inflammatory skin disease treatment.


Assuntos
Dermatite/tratamento farmacológico , Fármacos Dermatológicos/química , Fármacos Dermatológicos/uso terapêutico , Composição de Medicamentos/métodos , Animais , Humanos
7.
AAPS PharmSciTech ; 22(5): 201, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34231193

RESUMO

Particle engineering of excipients, at sub-particulate level using co-processing, can provide high functionality excipients. NanoCrySP technology has been recently explored as a novel approach for the generation of nanocrystalline solid dispersion of poorly soluble drugs, using spray drying process. The purpose of the present study was to generate co-processed mannitol and sorbitol (SD-CSM) using NanoCrySP technology having similar composition to commercial co-processed excipient (Compressol® SM, CP). The characterization of excipients was performed to evaluate their various physicomechanical properties. The sub-micron crystallite size of sorbitol in the matrix of mannitol was determined using the Williamson-Hall equation and Halder-Wagner equation. The reduction in crystallite size of sorbitol and mannitol, lower melting point, and lower heat of fusion of SD-CSM could be responsible for excellent compactibility, better tabletability, and comparable compressibility with respect to CP. This was confirmed by the compressibility-tabletability-compactibility (CTC) profile and Heckel plot analysis. Overall, SD-CSM generated using NanoCrySP technology improved functionalities of excipients over CP and would be useful for direct compression application.


Assuntos
Composição de Medicamentos/métodos , Manitol/química , Nanotecnologia , Sorbitol/química , Força Compressiva , Cristalização , Excipientes/química , Tamanho da Partícula , Porosidade , Comprimidos/química , Resistência à Tração , Molhabilidade
8.
AAPS PharmSciTech ; 22(5): 196, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184149

RESUMO

In a formulation, traces of peroxides in copovidone can impact the stability of drug substances that are prone to oxidation. The present study aimed to investigate the impact of peroxides in novel Plasdone™ S630 Ultra and compare it with regular Plasdone™ S630 on the oxidative degradation of quetiapine fumarate amorphous solid dispersions prepared via hot-melt extrusion technique. The miscibility of copovidones with drug was determined using the Hansen solubility parameter, and the results indicated a miscible drug-polymer system. Melt viscosity as a function of temperature was determined for the drug-polymer physical mixture to identify the suitable hot-melt extrusion processing temperature. The binary drug and polymer (30:70 weight ratio) amorphous solid dispersions were prepared at a processing temperature of 160°C. Differential scanning calorimetry and Fourier transform infrared spectroscopy studies of amorphous solid dispersions revealed the formation of a single-phase amorphous system with intermolecular hydrogen bonding between the drug and polymer. The milled extrudates were compressed into tablets by using extragranular components and evaluated for tabletability. Stability studies of the milled extrudates and tablet formulations were performed to monitor the oxidative degradation impurity (N-oxide). The N-oxide impurity levels in the quetiapine fumarate - Plasdone™ S630 Ultra milled extrudates and tablet formulations were reduced by 2- and 3-folds, respectively, compared to those in quetiapine fumarate - Plasdone™ S630. The reduced oxidative degradation and improved hot-melt extrusion processability of Plasdone™ S630 Ultra make it a better choice for oxidation-labile drugs over Plasdone™ S630 copovidone.


Assuntos
Tecnologia de Extrusão por Fusão a Quente/métodos , Excipientes Farmacêuticos/síntese química , Povidona/síntese química , Pirrolidinas/síntese química , Fumarato de Quetiapina/síntese química , Compostos de Vinila/síntese química , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Temperatura Alta , Oxirredução , Excipientes Farmacêuticos/farmacocinética , Povidona/farmacocinética , Pirrolidinas/farmacocinética , Fumarato de Quetiapina/farmacocinética , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Compostos de Vinila/farmacocinética
9.
AAPS PharmSciTech ; 22(5): 185, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34143327

RESUMO

Respiratory diseases are among the leading causes of morbidity and mortality worldwide. Innovations in biochemical engineering and understanding of the pathophysiology of respiratory diseases resulted in the development of many therapeutic proteins and peptide drugs with high specificity and potency. Currently, protein and peptide drugs are mostly administered by injections due to their large molecular size, poor oral absorption, and labile physicochemical properties. However, parenteral administration has several limitations such as frequent dosing due to the short half-life of protein and peptide in blood, pain on administration, sterility requirement, and poor patient compliance. Among various noninvasive routes of administrations, the pulmonary route has received a great deal of attention and is a better alternative to deliver protein and peptide drugs for treating respiratory diseases and systemic diseases. Among the various aerosol dosage forms, dry powder inhaler (DPI) systems appear to be promising for inhalation delivery of proteins and peptides due to their improved stability in solid state. This review focuses on the development of DPI formulations of protein and peptide drugs using advanced spray drying. An overview of the challenges in maintaining protein stability during the drying process and stabilizing excipients used in spray drying of proteins and peptide drugs is discussed. Finally, a summary of spray-dried DPI formulations of protein and peptide drugs, their characterization, various DPI devices used to deliver protein and peptide drugs, and current clinical status are discussed.


Assuntos
Peptídeos Catiônicos Antimicrobianos/síntese química , Composição de Medicamentos/métodos , Inaladores de Pó Seco/métodos , Proteínas Recombinantes/síntese química , Secagem por Atomização , Administração por Inalação , Aerossóis/química , Animais , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Dessecação/métodos , Excipientes/química , Humanos , Isoleucina/administração & dosagem , Isoleucina/síntese química , Manitol/administração & dosagem , Manitol/síntese química , Tamanho da Partícula , Peptídeos , Pós/química , Proteínas Recombinantes/administração & dosagem
10.
AAPS PharmSciTech ; 22(5): 190, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34159445

RESUMO

In direct compression of tablets, it is crucial to maintain content uniformity within acceptable margins, especially in formulations with low drug loading. To assure it, complex and multistep mixing processes are utilized in the industry. In this study, we suggest the use of a simple segregation test to evaluate mixing process performance and mixture segregation to produce tablets having satisfying content uniformity while keeping the process as simple and low cost as possible. Eventually, the formulation propensity to segregation can be evaluated using process analytical technology (PAT) to adjust the mixing process parameters to changing source drug properties. In this study, that approach was examined on a model drug with a broad batch-to-batch variability in particle size and shape. Excipients were chosen so that the resulting blend composition mimicked some marketed formulations. For each drug batch, two formulation blends were prepared through different preparation processes (one simple and one complex) and subsequently subjected to segregation tests. From those, segregation coefficients were obtained to compare segregation tendencies and homogeneity robustness between the drug batches and the blend preparation methods. The inter-particulate interactions were substantially influenced by the drug particle morphology and size and resulted in different segregation behavior. Based on these findings, a simple segregation test proved to be a useful tool for determining the suitability of different batches of the model drug to be used in a certain formulation. Moreover, for a particular batch A, the test revealed a potential for mixing process simplification and therefore process intensification and cost reduction.


Assuntos
Composição de Medicamentos/métodos , Excipientes/síntese química , Tamanho da Partícula , Tecnologia Farmacêutica/métodos , Pós , Pressão , Comprimidos
11.
AAPS PharmSciTech ; 22(5): 193, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184163

RESUMO

The human immunodeficiency virus (HIV) impacts up to 37 million people globally, of which 1.8 million are children. To date, there is no cure for HIV, although treatment options such as antiretroviral therapy (ART) are available. ART, which involves a patient taking a combination of antiretrovirals, is being used to treat HIV clinically. Despite the effectiveness of ART, there is currently no palatable pediatric formulation to treat HIV in children, which has hindered patient compliance and overall treatment efficacy. In addition, anti-HIV therapeutics are often poorly water-soluble, and hence have poor bioavailability. In the present study, we developed a pediatric-friendly formulation for anti-HIV therapeutics with improved dissolution characteristics of the therapeutic agents. Lopinavir (LPV) and ritonavir (RTV), available as FDA-approved fixed-dose combination products, were chosen as model ART drugs, and the formulation and processing parameters of spray-dried cyclodextrin (CD)-based LPV and RTV complexes were studied. Results showed that the spray-dried complexes exhibited enhanced dissolution profiles in comparison to pure drugs, particularly spray-dried ß-CD complexes, which showed the most favorable dissolution profiles. This current formulation with enhanced dissolution and taste-masking ability through the use of cyclodextrin has the potential to address the unmet need for the development of suitable pediatric formulations.


Assuntos
Fármacos Anti-HIV/análise , Fármacos Anti-HIV/síntese química , Ciclodextrinas/análise , Ciclodextrinas/síntese química , Desenvolvimento de Medicamentos/métodos , Secagem por Atomização , Fármacos Anti-HIV/uso terapêutico , Criança , Ciclodextrinas/uso terapêutico , Composição de Medicamentos/métodos , Infecções por HIV/tratamento farmacológico , Humanos , Espectroscopia de Ressonância Magnética/métodos , Pediatria/métodos , Difração de Raios X/métodos
12.
AAPS PharmSciTech ; 22(5): 183, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34132921

RESUMO

The current study evaluated the effect of location and amount of various superdisintegrants on the properties of tablets made by twin-screw melt granulation (TSMG). Sodium-croscarmellose (CCS), crospovidone (CPV), and sodium starch glycolate (SSG) were used in various proportions intra- and extra-granular. Tabletability, compactibility, compressibility as well as friability, disintegration, and dissolution performance were assessed. The extra-granular addition resulted in the fasted disintegration and dissolution. CPV performed superior to CCS and SSG. Even if the solid fraction (SF) of the granules was lower for CPV, only a minor decrease in tabletability was observed, due to the high plastic deformation of the melt granules. The intra-granular addition of CPV resulted in a more prolonged dissolution profile, which could be correlated to a loss in porosity during tableting. The 100% intra-granular addition of the CPV resulted in a distinct decrease of the disintegration efficiency, whereas the performance of SSG was unaffected by the granulation process. CCS was not suitable to be used for the production of an immediate-release formulation, when added in total proportion into the granulation phase, but its efficiency was less impaired compared to CPV. Shortest disintegration (78 s) and dissolution (Q80: 4.2 min) was achieved with CPV extra-granular. Using CPV and CCS intra-granular resulted in increased disintegration time and Q80. However, at a higher level of appx. 500 s and appx. 15 min, only SSG showed a process and location independent disintegration and dissolution performance.


Assuntos
Carboximetilcelulose Sódica/síntese química , Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Povidona/síntese química , Carboximetilcelulose Sódica/farmacocinética , Avaliação Pré-Clínica de Medicamentos/métodos , Excipientes/síntese química , Excipientes/farmacocinética , Excipientes Farmacêuticos/síntese química , Excipientes Farmacêuticos/farmacocinética , Porosidade , Povidona/farmacocinética , Solubilidade , Comprimidos , Resistência à Tração
13.
Molecules ; 26(11)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072733

RESUMO

Droplet microfluidics can produce highly tailored microparticles whilst retaining monodispersity. However, these systems often require lengthy optimisation, commonly based on a trial-and-error approach, particularly when using bio-instructive, polymeric surfactants. Here, micropipette manipulation methods were used to optimise the concentration of bespoke polymeric surfactants to produce biodegradable (poly(d,l-lactic acid) (PDLLA)) microparticles with unique, bio-instructive surface chemistries. The effect of these three-dimensional surfactants on the interfacial tension of the system was analysed. It was determined that to provide adequate stabilisation, a low level (0.1% (w/v)) of poly(vinyl acetate-co-alcohol) (PVA) was required. Optimisation of the PVA concentration was informed by micropipette manipulation. As a result, successful, monodisperse particles were produced that maintained the desired bio-instructive surface chemistry.


Assuntos
Portadores de Fármacos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Polímeros/química , Álcool de Polivinil/química , Tensoativos/química , Materiais Biocompatíveis/química , Biodegradação Ambiental , Composição de Medicamentos/métodos , Ácido Láctico/química , Microfluídica , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Ácido Poliglicólico/química , Solventes , Propriedades de Superfície , Tensão Superficial
14.
AAPS PharmSciTech ; 22(5): 184, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34142250

RESUMO

Hot-melt extrusion has found extensive application as a feasible pharmaceutical technological option over recent years. HME applications include solubility enhancement, taste masking, and sustained drug release. As bioavailability enhancement is a hot topic of today's science, one of the main applications of HME is centered on amorphous solid dispersions. This review describes the most significant aspects of HME technology and its use to prepare solid dispersions as a drug formulation strategy to enhance the solubility of poorly soluble drugs. It also addresses molecular and thermodynamic features critical for the physicochemical properties of these systems, mainly in what concerns miscibility and physical stability. Moreover, the importance of applying the Quality by Design philosophy in drug development is also discussed, as well as process analytical technologies in pharmaceutical HME monitoring, under the current standards of product development and regulatory guidance. Graphical Abstract.


Assuntos
Química Farmacêutica/métodos , Portadores de Fármacos/síntese química , Desenvolvimento de Medicamentos/métodos , Tecnologia de Extrusão por Fusão a Quente/métodos , Disponibilidade Biológica , Composição de Medicamentos/métodos , Composição de Medicamentos/tendências , Tecnologia de Extrusão por Fusão a Quente/tendências , Temperatura Alta , Solubilidade , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/tendências , Termodinâmica
15.
Molecules ; 26(10)2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-34065944

RESUMO

Stable, oil-in-water nanoemulsions containing astaxanthin (AsX) were produced by intense fluid shear forces resulting from pumping a coarse reagent emulsion through a self-throttling annular gap valve at 300 MPa. Compared to crude emulsions prepared by conventional homogenization, a size reduction of over two orders of magnitude was observed for AsX-encapsulated oil droplets following just one pass through the annular valve. In krill oil formulations, the mean hydrodynamic diameter of lipid particles was reduced to 60 nm after only two passes through the valve and reached a minimal size of 24 nm after eight passes. Repeated processing of samples through the valve progressively decreased lipid particle size, with an inflection in the rate of particle size reduction generally observed after 2-4 passes. Krill- and argan oil-based nanoemulsions were produced using an Ultra Shear Technology™ (UST™) approach and characterized in terms of their small particle size, low polydispersity, and stability.


Assuntos
Antioxidantes/química , Clorofíceas/química , Composição de Medicamentos/métodos , Extratos Vegetais/química , Óleos Vegetais/química , Água/química , Animais , Estabilidade de Medicamentos , Emulsões , Euphausiacea/química , Tamanho da Partícula , Xantofilas/química
16.
Molecules ; 26(11)2021 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-34067434

RESUMO

The flexibility of dose and dosage forms makes 3D printing a very interesting tool for personalized medicine, with fused deposition modeling being the most promising and intensively developed method. In our research, we analyzed how various types of disintegrants and drug loading in poly(vinyl alcohol)-based filaments affect their mechanical properties and printability. We also assessed the effect of drug dosage and tablet spatial structure on the dissolution profiles. Given that the development of a method that allows the production of dosage forms with different properties from a single drug-loaded filament is desirable, we developed a method of printing ketoprofen tablets with different dose and dissolution profiles from a single feedstock filament. We optimized the filament preparation by hot-melt extrusion and characterized them. Then, we printed single, bi-, and tri-layer tablets varying with dose, infill density, internal structure, and composition. We analyzed the reproducibility of a spatial structure, phase, and degree of molecular order of ketoprofen in the tablets, and the dissolution profiles. We have printed tablets with immediate- and sustained-release characteristics using one drug-loaded filament, which demonstrates that a single filament can serve as a versatile source for the manufacturing of tablets exhibiting various release characteristics.


Assuntos
Química Farmacêutica/métodos , Cetoprofeno/química , Cetoprofeno/síntese química , Impressão Tridimensional , Comprimidos , Varredura Diferencial de Calorimetria , Preparações de Ação Retardada , Composição de Medicamentos/métodos , Desenho de Fármacos , Liberação Controlada de Fármacos , Elasticidade , Excipientes/química , Álcool de Polivinil , Medicina de Precisão , Reprodutibilidade dos Testes , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Difração de Raios X , Microtomografia por Raio-X
17.
Molecules ; 26(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073703

RESUMO

Besides their best-known uses in the food and fermentation industry, yeasts have also found application as microcapsules. In the encapsulation process, exogenous and most typically hydrophobic compounds diffuse and end up being passively entrapped in the cell body, and can be released upon application of appropriate stimuli. Yeast cells can be employed either living or dead, intact, permeabilized, or even emptied of all their original cytoplasmic contents. The main selling points of this set of encapsulation technologies, which to date has predominantly targeted food and-to a lesser extent-pharmaceutical applications, are the low cost, biodegradability and biocompatibility of the capsules, coupled to their sustainable origin (e.g., spent yeast from brewing). This review aims to provide a broad overview of the different kinds of yeast-based microcapsules and of the main physico-chemical characteristics that control the encapsulation process and its efficiency.


Assuntos
Composição de Medicamentos/métodos , Leveduras/citologia , Interações Hidrofóbicas e Hidrofílicas
18.
Int J Mol Sci ; 22(9)2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068733

RESUMO

Wound infections are considered a major cause for wound-associated morbidity. There is a high demand for alternative, robust, and affordable methods that can provide relatable and reproducible results when testing topical treatments, both in research and in the pharmaceutical industry. Here we present an ex vivo wound infection model using porcine skin and a burn wounding method, allowing for the efficacy evaluation of topical antimicrobial formulations. Utilizing this model, we demonstrate the potential of topical treatments after infecting the wounds with clinically significant bacteria, P. aeruginosa and S. aureus. We show that the method is compatible with several analytical tools used to analyze infection and antimicrobial effects. Both bacterial strains successfully infected the wound surface, as well as deeper regions of the tissue. Quantification of viable bacteria on the wound surface and in the tissue, longitudinal measurements of bioluminescence, fluorescence microscopy, and scanning electron microscopy were used to confirm the effects of antibacterial treatments. Furthermore, we show that biofilms are formed on the wound surface, indicating that the demonstrated method mirrors typical in vivo infections.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Queimaduras/tratamento farmacológico , Infecção dos Ferimentos/tratamento farmacológico , Administração Tópica , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Queimaduras/patologia , Modelos Animais de Doenças , Composição de Medicamentos/métodos , Humanos , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Suínos , Cicatrização/efeitos dos fármacos , Infecção dos Ferimentos/microbiologia , Infecção dos Ferimentos/patologia
19.
AAPS PharmSciTech ; 22(5): 168, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34080070

RESUMO

Formulation development of KO-947-K mesylate injectable drug products was described. Solution formulations were initially attempted, and key parameters such as drug concentration, buffer, pH, complexing agent, and tonicity modifying agent were carefully evaluated in the lab setting, mainly focusing on solubility and chemical stability. A lead solution formulation was advanced to a scaleup campaign. An unexpected stability issue was encountered, and the root cause was attributed to the heterogeneous liquid freezing process of the formulated solution at -20°C, which had not been captured in the lab setting. A lyophilized product was then designed to overcome the issue and supplied to the phase I clinical trial.


Assuntos
Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Desenvolvimento de Medicamentos/métodos , Inibidores Enzimáticos/síntese química , Estabilidade de Medicamentos , Inibidores Enzimáticos/administração & dosagem , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Liofilização , Congelamento , Injeções , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/síntese química , Solubilidade
20.
Mol Pharm ; 18(6): 2448-2453, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33983745

RESUMO

Nanomedicine has demonstrated a substantial role in vaccine development against severe acute respiratory syndrome coronavirus (SARS-CoV-2 and COVID-19). Although nanomedicine-based vaccines have now been validated in millions of individuals worldwide in phase 4 and tracking of sex-disaggregated data on COVID-19 is ongoing, immune responses that underlie COVID-19 disease outcomes have not been clarified yet. A full understanding of sex-role effects on the response to nanomedicine products is essential to building an effective and unbiased response to the pandemic. Here, we exposed model lipid nanoparticles (LNPs) to whole blood of 18 healthy donors (10 females and 8 males) and used flow cytometry to measure cellular uptake by circulating leukocytes. Our results demonstrated significant differences in the uptake of LNP between male and female natural killer (NK) cells. The results of this proof-of-concept study show the importance of recipient sex as a critical factor which enables researchers to better consider sex in the development and administration of vaccines for safer and more-efficient sex-specific outcomes.


Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Nanopartículas/química , SARS-CoV-2/imunologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/química , Composição de Medicamentos/métodos , Ácidos Graxos Monoinsaturados/química , Feminino , Voluntários Saudáveis , Humanos , Imunogenicidade da Vacina , Lipossomos , Masculino , Pandemias/prevenção & controle , Compostos de Amônio Quaternário/química , Fatores Sexuais , Resultado do Tratamento
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