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1.
Pharm Res ; 40(10): 2355-2370, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37131104

RESUMO

BACKGROUND: Spray-drying is considered a promising alternative drying method to lyophilization (freeze-drying) for therapeutic proteins. Particle counts in reconstituted solutions of dried solid dosage forms of biologic drug products are closely monitored to ensure product quality. We found that high levels of particles formed after reconstitution of protein powders that had been spray-dried under suboptimal conditions. METHODS: Visible and subvisible particles were evaluated. Soluble proteins in solution before spray-drying and in the reconstituted solution of spray-dried powder were analyzed for their monomer content levels and melting temperatures. Insoluble particles were collected and analyzed by Fourier transform infrared microscopy (FTIR), and further analyzed with hydrogen-deuterium exchange (HDX). RESULTS: Particles observed after reconstitution were shown not to be undissolved excipients. FTIR confirmed their identity as proteinaceous in nature. These particles were therefore considered to be insoluble protein aggregates, and HDX was applied to investigate the mechanism underlying aggregate formation. Heavy-chain complementarity-determining region 1 (CDR-1) in the aggregates showed significant protection by HDX, suggesting CDR-1 was critical for aggregate formation. In contrast, various regions became more conformationally dynamic globally, suggesting the aggregates have lost protein structural integrity and partially unfolded after spray-drying. DISCUSSION: The spray-drying process could have disrupted the higher-order structure of proteins and exposed the hydrophobic residues in CDR-1 of the heavy chain, contributing to the formation of aggregate through hydrophobic interactions upon reconstitution of spray-dried powder. These results can contribute to efforts to design spray-dry resilient protein constructs and improve the robustness of the spray-drying process.


Assuntos
Microscopia , Proteínas , Pós/química , Liofilização , Tamanho da Partícula
2.
Drug Dev Ind Pharm ; 49(7): 467-478, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37421633

RESUMO

OBJECTIVE: This study was carried out to transform the hydrolyzed pea protein into a pharmaceutical tablet form by masking methylprednisolone. SIGNIFICANCE: This study provides some crucial contributions in showing how functional excipients such as pea protein, which are generally used in food industries, can be used in pharmaceutical product formulations and their effects. METHODS: Methylprednisolone was formulated using spray drying technology. Design Expert Software (Version 13) was used for the statistical analysis. The in vitro cytotoxic effects for NIH/3T3 mouse fibroblast cells were investigated by XTT cell viability assay. HPLC was used to analyze the Caco-2 permeability studies and dissolution tests. RESULTS: The optimum formulation was evaluated against the reference product by performing cytotoxicity and cell permeability studies. According to our test results, Papp (apparent permeability) values of Methylprednisolone were measured around 3 × 10-6 cm/s and Fa (fraction absorbed) values around 30%. These data indicate that Methylprednisolone HCl has 'moderate permeability' and our study confirmed that it could have belonged to BCS Class II-IV since both low solubility and moderate permeability. CONCLUSION: The findings offer valuable information to guide and inform the use of pea protein in pharmaceutical formulations. Significant effects on methylprednisolone tablet formulation designed with the philosophy of quality by design (QbD) of pea protein have been demonstrated by both in vitro and cell studies.


Assuntos
Proteínas de Ervilha , Humanos , Animais , Camundongos , Células CACO-2 , Comprimidos , Permeabilidade , Metilprednisolona/farmacologia , Solubilidade
3.
Molecules ; 27(7)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35408595

RESUMO

The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient's preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (Dh) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of Dh is improved when measured at the spray dryer outlet temperature compared to room temperature (R2 = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying.


Assuntos
Proteínas , Água , Emulsões , Tamanho da Partícula , Pós , Solventes , Temperatura , Água/química
5.
Pharm Dev Technol ; 25(2): 245-251, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31690150

RESUMO

Poor solubility and bioavailability of drugs are often affected by its microscopic structural properties. Nitrofurantoin (NF), a Biopharmaceutics Classification System class II item, has a low water solubility with low plasma concentrations. To improve its therapeutic efficacy, formulation strategy of solid dispersion (SD) and co-crystallization are compared herein. The co-crystal is prepared with citric acid in 1:1 stoichiometric ratio while SD consists of 30% w/w nitrofurantoin and 70% w/w hydroxypropyl methylcellulose (HPMC) as the carrier system. As a control, the physical mixture of NF and HPMC was prepared. All the preparations were characterized with differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), microscopy analysis, solubility, and dissolution studies. The formation of co-crystal, solvent evaporated, and spray-dried SD are confirmed by the ATR-FTIR where peaks shifting of several functional groups indicate the formation of the hydrogen bond. Dissolution studies showed a greater initial dissolution rate in co-crystal than SD despite the possible presence of amorphous content in the SD system. Overall, co-crystal is concluded to be a better approach than SD for an effective dissolution.


Assuntos
Nitrofurantoína/química , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Cristalização/métodos , Composição de Medicamentos/métodos , Derivados da Hipromelose/química , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Solubilidade/efeitos dos fármacos , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
6.
Drug Dev Ind Pharm ; 45(6): 1029-1037, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30913921

RESUMO

The waste of inedible parts of pineapple, particularly in tropical countries, contributes to environmental burden. This study aimed to utilize pineapple stem waste as a source of starch-based pharmaceutical excipient. The starch was isolated from pineapple stem waste using a simple process without applying harsh chemicals. The isolated starch (PSS) was then physically modified through gelatinization and spray drying to improve its physical properties. Starch characteristics were identified by FTIR, TGA, and XRD analysis. The SEM imaging showed morphological change with reduced surface roughness due to physical modification of the starch. Decreased crystallinity of modified starch (MPS) was confirmed by our XRD results: the peaks of A-type crystalline at 2θ of 13°, 15°, 18°, and 23° were present in PSS, yet mostly absent in MPS. Thermogravimetric analysis showed that MPS behaved differently from PSS and the degradation events occurred at lower temperature. When the starch was spray-dried without prior gelatinization process, the physicochemical characteristics of spray-dried starch resembled untreated starch. Moisture content in PSS (10.66%) decreased after gelatinization to 7.3%. Potential use of MPS was demonstrated by its powder flowability (Student's t test, p < 0.05), swelling capacity (Student's t test, p < 0.05), and compaction profile. In summary, our findings demonstrated that modified pineapple starch showed better physical characteristics and quite promising as a tablet binder and disintegrant.


Assuntos
Ananas/química , Química Farmacêutica/métodos , Excipientes/química , Química Verde/métodos , Amido/química , Varredura Diferencial de Calorimetria , Cristalização , Excipientes/isolamento & purificação , Caules de Planta/química , Pós , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Amido/isolamento & purificação , Comprimidos , Difração de Raios X
7.
J Microencapsul ; 36(5): 485-499, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31318306

RESUMO

In this study, we produced curcumin loaded gelatine microparticles, through spray-drying method, with dialdehyde carboxymethyl cellulose (DCMC) which is introduced as a new cross-linking agent for drug delivery systems and examined toxicities by comparison of traditional cross-linking agents. We employed various parameters in the production and tried to develop the most efficient drug delivery system through Taguchi method by examining efficiencies on gastric cancer under in vitro conditions. The results indicated gelatine microparticles cross-linked with DCMC offers more biocompatible drug delivery systems. The particle size of the microparticles produced via different parameters varies from 1.926 to 3.357 µm. Curcumin was substantially remained stable after 6 months. This study indicates potential use of DCMC cross-linked gelatine microparticles as drug delivery vehicle.


Assuntos
Antineoplásicos/administração & dosagem , Carboximetilcelulose Sódica/química , Curcumina/administração & dosagem , Preparações de Ação Retardada/química , Gelatina/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Reagentes de Ligações Cruzadas/química , Curcumina/química , Curcumina/farmacologia , Liberação Controlada de Fármacos , Humanos , Neoplasias/tratamento farmacológico
8.
J Dairy Sci ; 101(10): 8822-8836, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30122413

RESUMO

The objective of this work is to determine the extent to which changes in the skim milk powder (SMP) manufacturing process alter the volatile profile of SMP, and whether these changes are carried through to a final product when the SMP is used as an ingredient and subjected to further processing. The manufacture of SMP is a multistage process involving a preliminary concentration step, heat treatment, and a drying stage. However, the methods and conditions used by the industry are not standardized, and the inherent variability in the production of SMP has consequences for the end-users, such as the confectionery industry, where the SMP is used as an ingredient during the production of milk chocolate, white chocolate, and caramel. This study investigates the effect of each stage of the manufacturing process on the concentration of reducing sugars and available amino groups (as precursors of the Maillard reaction) as well as on the volatile products of the Maillard reaction and lipid degradation. Eight types of SMP were produced using combinations of different processing conditions: concentration (by evaporation or reverse osmosis), heat treatment (low heat or high heat), and drying (spray-drying or freeze-drying). Maillard precursors were quantified after each processing stage and volatile compounds were extracted using solid-phase microextraction, and analyzed by gas chromatography-mass spectrometry. The resulting SMP were incorporated into a model white chocolate system, produced under varying conching conditions. We demonstrate not only that changes in the SMP manufacturing conditions affect the volatile profile of SMP, but also that these differences can be carried through to a final product when the SMP is used to prepare a model white chocolate. Understanding these differences is important to the industry for controlling the flavor of the end product.


Assuntos
Chocolate , Análise de Alimentos/métodos , Manipulação de Alimentos/métodos , Leite/química , Compostos Orgânicos Voláteis/análise , Animais , Chocolate/análise , Aromatizantes , Odorantes/análise , Pós , Paladar
9.
Drug Dev Ind Pharm ; 43(7): 1103-1111, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28276783

RESUMO

OBJECTIVES: Dry powder formulations are extensively used to improve the stability of antibodies. Spray drying is one of important methods for protein drying. This study investigated the effects of trehalose, hydroxypropyl beta cyclodextrin (HPBCD) and beta cyclodextrin (BCD) on the stability and particle properties of spray-dried IgG. METHODS: D-optimal design was employed for both experimental design and analysis and optimization of the variables. The size and aerodynamic behavior of particles were determined using laser light scattering and glass twin impinger, respectively. In addition, stability, ratio of beta sheets and morphology of antibody were analyzed using size exclusion chromatography, IR spectroscopy and electron microscopy, respectively. RESULTS: Particle properties and antibody stability were significantly improved in the presence of HPBCD. In addition, particle aerodynamic behavior, in terms of fine-particle fraction (FPF), enhanced up to 52.23%. Furthermore, antibody was better preserved not only during spray drying, but also during long-term storage. In contrast, application of BCD resulted in the formation of larger particles. Although trehalose caused inappropriate aerodynamic property, it efficiently decreased antibody aggregation. CONCLUSION: HPBCD is an efficient excipient for the development of inhalable protein formulations. In this regard, optimal particle property and antibody stability was obtained with proper combination of cyclodextrins and simple sugars, such as trehalose.


Assuntos
Anticorpos/química , Ciclodextrinas/química , Pós/química , Trealose/química , beta-Ciclodextrinas/química , Administração por Inalação , Varredura Diferencial de Calorimetria , Química Farmacêutica , Dessecação , Estabilidade de Medicamentos , Excipientes/química , Tamanho da Partícula
10.
Pharm Res ; 33(6): 1447-55, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26975360

RESUMO

PURPOSE: Previously, a respirable powder (RP) formulation of pirfenidone (PFD) was developed for reducing phototoxic risk; however, PFD-RP demonstrated unacceptable in vitro inhalation performance. The present study aimed to develop a new RP system of PFD with favorable inhalation properties by spray-drying method. METHODS: Spray-dried PFD (SD/PFD) was prepared by spray-drying with L-leucine, and the physicochemical properties and efficacy in an antigen-sensitized airway inflammation model were assessed. A pharmacokinetic study was also conducted after intratracheal and oral administration of PFD formulations. RESULTS: Regarding powder characterization, SD/PFD had dimpled surface with the mean diameter of 1.793 µm. In next generation impactor analysis, SD/PFD demonstrated high in vitro inhalation performance without the need of carrier particles, and the fine particle fraction of SD/PFD was calculated to be 62.4%. Insufflated SD/PFD (0.3 mg-PFD/rat) attenuated antigen-evoked inflammatory events in the lung, including infiltration of inflammatory cells and myeloperoxidase activity. Systemic exposure level of PFD after insufflation of SD/PFD at the pharmacologically effective dose was 600-fold lower than that after oral administration of PFD at the phototoxic dose. CONCLUSION: SD/PFD would be suitable for inhalation, and the utilization of an RP system with SD/PFD would provide a safer medication compared with oral administration of PFD.


Assuntos
Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Dessecação , Pneumonia/prevenção & controle , Piridonas/administração & dosagem , Piridonas/farmacocinética , Tecnologia Farmacêutica/métodos , Administração por Inalação , Administração Oral , Aerossóis , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/toxicidade , Líquido da Lavagem Broncoalveolar/imunologia , Cromatografia Líquida , Modelos Animais de Doenças , Composição de Medicamentos , Masculino , Ovalbumina , Tamanho da Partícula , Peroxidase/metabolismo , Pneumonia/sangue , Pneumonia/induzido quimicamente , Pneumonia/imunologia , Pós , Piridonas/química , Piridonas/toxicidade , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray
11.
Pharm Res ; 33(11): 2763-76, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27450412

RESUMO

PURPOSE: This work examines the relevance of viral activity in the optimization of spray drying process parameters for the development of thermally stable vaccine powders. In some instances, the actual active pharmaceutical ingredient (API) is not included in the process optimization as it is deemed too costly to use until the final selection of operating conditions, however, that approach is inappropriate for highly labile biopharmaceutics. We investigate the effects of spray drying parameters on i) yield, ii) particle size and iii) viral vector activity of a mannitol/dextran encapsulated recombinant human type 5 adenoviral vector vaccine, to demonstrate the effects and magnitude of each effect on the three responses, and further show that the API must be included earlier in the optimization. METHODS: A design of experiments approach was used with response surface methodology (RSM) to optimize parameters including inlet temperature, spray gas flow rate, liquid feed rate and solute concentration in the feed. RESULTS: In general, good conditions for maintaining viral activity led to reduced yield and fewer particles of the desired size. Within the range of parameters tested, the yield varied from 50 to 90%, the percentage of ideally size particles was 10-50%, and the viral vector titre loss was 0.25-4.0 log loss. CONCLUSIONS: RSM indicates that the most significant spray drying parameters are the inlet temperature and spray gas flow rate. It was not possible to optimize all three output variables with one set of parameters, indicating that there will only be one dominant criteria for processing which in the case of viral vaccines will likely be viral vector activity.


Assuntos
Adenoviridae/genética , Vetores Genéticos , Pós/química , Células A549 , Adenoviridae/fisiologia , Dessecação/instrumentação , Dextranos/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Humanos , Manitol/química , Tamanho da Partícula , Temperatura , Vacinas
12.
Pharm Dev Technol ; 21(7): 803-811, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26135384

RESUMO

A mini-scale spray dryer, the ProCept 4M8, with a 1.4 m or 2.1 m drying chamber length has been used to prepare large, flowable particles of catalase, trehalose or lactose. A 25 kHz ultrasonic nozzle or a Rayleigh breakup mono-disperse droplet generator was used for atomization. The ultrasonic nozzle produced dried particles of average diameter ≥30 µm that show incipient flow behavior when measured with the vibrating spatula method. A high solute concentration of 69% w/w in the liquid feed was required, which is readily achievable with trehalose but not with the viscous catalase solution. At lower solute concentrations, e.g. 20% w/w, the mono-disperse droplet generator was able to produce well flowable particles of approximately 50 µm diameter, although with a low yield. This is a result of collisions between the droplets falling through the drying chamber when then coalesce. It is possible to produce dried, flowable particles in milligram quantities on a mini-scale spray dryer such as the ProCept using the 25 kHz ultrasonic nozzle. With the mono-disperse droplet generator the long drying chamber ensures a residence time of a number of seconds, but this also allows droplet coalescence at fall heights >40 cm.


Assuntos
Proteínas/química , Tecnologia Farmacêutica/métodos , Catalase/química , Química Farmacêutica/métodos , Lactose/química , Tamanho da Partícula , Trealose/química
13.
Drug Dev Ind Pharm ; 40(6): 749-57, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23596974

RESUMO

The spray-drying behaviour of 16 water-miscible organic solvents on a bench-scale machine (Büchi B290 with inert loop) was determined under mild-to-moderate process conditions, namely inlet gas temperature of 130 °C and liquid feed flow rate of ≤3 mL/min. The solvents with boiling points below the inlet gas temperature could be fully dried (Group 1 solvents). The two exceptions were DMSO and DMF which despite their higher boiling points could be fully dried. The remaining solvents with boiling points above the inlet gas temperature were not fully dried during passage through the spray-dryer (Group 2 solvents). Trypsin and lysozyme when spray-dried from Group 1 solvent binary mixtures with water showed similar inactivation and residual water content, independent of solvent. The level of residual solvent was, however, strongly dependent on solvent. Trehalose (20%) and mannitol (10%) could be spray-dried from DMSO/water binary mixtures, but the amorphous disaccharide required higher inlet gas temperature. Trehalose/trypsin and mannitol/trypsin formulations showed differing degrees of protection against enzyme inactivation when spray-dried from Group 1 solvent binary mixtures with water. In all solvents the mannitol protected as well, if not better, than the trehalose. This study identifies some suitable organic solvents for spray-drying protein formulations, but also shows the difficulties of remaining organic solvent under the moderate inlet gas temperature used.


Assuntos
Carboidratos/química , Química Farmacêutica/métodos , Enzimas/química , Solventes/química , Água/química , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Microscopia Eletrônica de Varredura , Compostos Orgânicos/química , Pós , Solubilidade , Especificidade por Substrato , Propriedades de Superfície , Temperatura , Temperatura de Transição
14.
Anim Biosci ; 37(8): 1440-1451, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38575120

RESUMO

OBJECTIVE: This study aimed to develop and evaluate the effectiveness of a water-soluble microencapsulation method for probiotic strains using gum Arabic (GA) and skim milk (SKM) over a three-month storage period following processing. METHODS: Four strains of Pediococcus acidilactici (BYF26, BYF20, BF9, and BF14) that were typical lactic acid bacteria (LAB) isolated from the chicken gut were mixed with different ratios of GA and SKM as coating agents before spray drying at an inlet temperature 140°C. After processing, the survivability and probiotic qualities of the strains were assessed from two weeks to three months of storage at varied temperatures, and de-encapsulation was performed to confirm the soluble properties. Finally, the antibacterial activity of the probiotics was assessed under simulated gastrointestinal conditions. RESULTS: As shown by scanning electron microscopy, spray-drying produced a spherical, white-yellow powder. The encapsulation efficacy (percent) was greatest for a coating containing a combination of 30% gum Arabic: 30% skim milk (w/v) (GA:SKM30) compared to lower concentrations of the two ingredients (p<0.05). Coating with GA:SKM30 (w/v) significantly enhanced (p<0.05) BYF26 survival under simulated gastrointestinal conditions (pH 2.5 to 3) and maintained higher survival rates compared to non-encapsulated cells under an artificial intestinal juices condition of pH 6. De-encapsulation tests indicated that the encapsulated powder dissolved in water while keeping viable cell counts within the effective range of 106 for 6 hours. In addition, following three months storage at 4°C, microencapsulation of BYF26 in GA:SKM30 maintained both the number of viable cells (p<0.05) and the preparation's antibacterial efficacy against pathogenic bacteria, specifically strains of Salmonella. CONCLUSION: Our prototype water-soluble probiotic microencapsulation GA:SKM30 effectively maintains LAB characteristics and survival rates, demonstrating its potential for use in preserving probiotic strains that can be used in chickens and potentially in other livestock.

15.
Int J Pharm ; 652: 123836, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38266940

RESUMO

The most common influenza vaccines are inactivated viruses produced in chicken eggs, which is a time-consuming production method with variable efficacy due to mismatches of the vaccine strains to the dominant circulating strains. Subunit-based vaccines provide faster production times in comparison to the traditional egg-produced vaccines but often require the use of an adjuvant to elicit a highly protective immune response. However, the current FDA approved adjuvant for influenza vaccines (MF59) elicits a primarily helper T-cell type 2 (Th2)-biased humoral immune response. Adjuvants that can stimulate a Th1 cellular response are correlated to have more robust protection against influenza. The cyclic dinucleotide cGAMP has been shown to provide a potent Th1 response but requires the use of a delivery vehicle to best initiate its signalling pathway in the cytosol. Herein, acetalated dextran (Ace-DEX) was used as the polymer to fabricate microparticles (MPs) via double-emulsion, electrospray, and spray drying methods to encapsulate cGAMP. This study compared each fabrication method's ability to encapsulate and retain the hydrophilic adjuvant cGAMP. We compared their therapeutic efficacy to Addavax, an MF59-like adjuvant, and cGAMP Ace-DEX MPs provided a stronger Th1 response in vaccinated BALB/c mice. Furthermore, we compared Ace-DEX MPs to spray dried MPs composed from a commonly used polymer for drug delivery, poly(lactic-co-glycolic acid) (PLGA). We observed that all Ace-DEX MPs elicited similar humoral and cellular responses to the PLGA MPs. Overall, the results shown here indicate Ace-DEX can perform similarly to PLGA as a polymer for drug delivery and that spray drying can provide an efficient way to produce MPs to encapsulate cGAMP and stimulate the immune system.


Assuntos
Vacinas contra Influenza , Influenza Humana , Esqualeno , Animais , Camundongos , Humanos , Dextranos , Polissorbatos , Vacinas de Subunidades Antigênicas , Adjuvantes Imunológicos , Adjuvantes Farmacêuticos
16.
J Food Sci ; 88(3): 1172-1187, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36651875

RESUMO

Chronic inflammation is linked to the development of numerous diseases and is accompanied by increased cytokine secretion. Macrophages provide a first line of defense against pathogens that under inflammatory stimuli release pro-inflammatory cytokines. The essential oil (EO) fractions obtained from Citrus spp. rich in different compounds have gained the attention of both researchers and users during the last decades. In particular, grapefruit (Citrus paradisi) peel is rich in phenolics and flavonoids with several health benefits, including anti-inflammatory actions. Additionally, its EO consists of a large number of compounds such as monoterpenes, sesquiterpenes, alcohols, aldehydes, esters, and oxides. Among the methods for encapsulating EOs, spray-drying is the main one. In the present study, we aimed to determine the in vitro anti-inflammatory activity of EO from C. paradisi (grapefruit essential oil [GEO]) (whole and fractions) in a lipopolysaccharide (LPS)-induced inflammation model. Results indicate that Fr-GEO and Fr-GEO_SD exert protective effects against LPS-induced inflammation by decreasing gene expression and levels of pro-inflammatory cytokines as IL-6 and TNF-α. Monoterpenes as the most common components, as well as aldehydes and sesquiterpenes, might be responsible for such effects, although a synergistic action is not excluded. Furthermore, a higher percent of aldehydes is linked to improved olfactory properties. Our findings support the anti-inflammatory effects of selected Fr-GEO with a great potential for the development of new nutraceuticals and/or functional food for the treatment of inflammatory-associated diseases. PRACTICAL APPLICATION: The findings of this study support the anti-inflammatory effects of selected Fr-GEO with a great potential for the development of new nutraceuticals and/or functional food for the treatment of inflammatory-associated diseases.


Assuntos
Citrus paradisi , Óleos Voláteis , Óleos Voláteis/farmacologia , Aldeídos/farmacologia , Lipopolissacarídeos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Monoterpenos , Citocinas
17.
Heliyon ; 9(6): e16674, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37274654

RESUMO

Pro-liposome is a type of drug delivery system (DDS) with numerous advantages as a stable material with various applicability for several pharmaceutical dosage forms, to effectively deliver the material to reach its target in the human body. Nevertheless, it is mostly designed by employing an organic solvent hence giving rise to safety issues. We have developed a method for the preparation of organic solvent-free liposomes composed of soy lecithin and cholesterol by highlighting the importance of temperature during the initial mixing process, a self-hydration of a thin layer spread film, and a spray-drying technique with a suitable excipient as the carrier. The method was successfully applied to prepare a stable pro-liposome containing 0.17% (w/w) of piperine with an encapsulation efficiency of 95.58 ± 2.91%. Moreover, the study revealed that a piperine molecule forms hydrophobic interaction with six of the adjacent phospholipids in the liposome structure, this information can be useful for researchers designing similar studies. In conclusion, organic solvent-free pro-liposome can be an alternative method in the development of DDS, and several factors could be continuously improved to fulfill the intended pro-liposome characteristic.

18.
Foods ; 11(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37430918

RESUMO

Bovine lactoferricin-lactoferrampin-encoding Lactobacillus reuteri (LR-LFCA) has been found to benefit its host by strengthening its intestinal barrier. However, several questions remain open concerning genetically engineered strains maintaining long-term biological activity at room temperature. In addition, probiotics are vulnerable to harsh conditions in the gut, such as acidity and alkalinity, and bile salts. Microencapsulation is a technique to entrap probiotic bacteria into gastro-resistant polymers to carry them directly to the intestine. We selected nine kinds of wall material combinations to encapsulate LR-LFCA by spray drying microencapsulation. The storage stability, microstructural morphology, biological activity, and simulated digestion in vivo or in vitro of the microencapsulated LR-LFCA were further evaluated. The results showed that LR-LFCA had the highest survival rate when microcapsules were prepared using a wall material mixture (skim milk, sodium glutamate, polyvinylpyrrolidone, maltodextrin, and gelatin). Microencapsulated LR-LFCA increased the stress resistance capacity and colonization abilities. In the present study, we have identified a suitable wall material formulation for spray-dried microencapsulation of genetically engineered probiotic products, which would facilitate their storage and transport.

19.
Drug Deliv ; 29(1): 3384-3396, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36415157

RESUMO

Pirfenidone (PRF) is the first FDA-approved API in the treatment of idiopathic pulmonary fibrosis (IPF). However, PRF induces serious side effects, such as photophobia and gastrointestinal disorder. PRF inhalation can be expected with a lower effective dose and reduced side effects. In this study, PRF was prepared as inhalable co-spray-dried particles for dry powder inhalation. Mannitol, L-leucine (Leu), and NaCl were used as a stabilizer. The kinds and ratios of stabilizers affecting the physicochemical properties of particles were analyzed, including particle size and surface composition, because of the surface enrichment properties of Leu, the most effective stabilizer. The co-spray-dried PRF and Leu microparticle (SD-PL1:1) have the smallest size and highest aerosol performance. The bioavailability was confirmed by in vivo pharmacokinetics (PK) studies. In addition, in vivo pharmacodynamics (PD) experiments were conducted using a bleomycin-induced IPF rat model. In vivo PK experiments demonstrated that pulmonary administration of SD-PL1:1 was 4 times more effective than the oral route. Similar to the PK results, the therapeutic effect was improved when SD-PL1:1 was administered via the pulmonary route compared to the oral route.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Piridonas , Ratos , Animais , Piridonas/farmacologia , Disponibilidade Biológica , Bleomicina , Excipientes
20.
Curr Res Food Sci ; 5: 1713-1719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212080

RESUMO

In the current research, Enterococcus mundtii SRBG1 newly isolated from Bat guano was encapsulated using spray drying technique to create a probiotic powder using six combinations of inulin, maltodextrin and sodium alginate. The encapsulation yield, moisture content, physical characteristics, and shape were investigated. Microcapsules yields ranged from 67 to 85 percent, which is consistent with typical B-290 spray-drier yields. The moisture content showed to increase (4 ± 0.15%) with the addition of sodium alginate to inulin and maltodextrin. In the gastrointestinal conditions (simulated gastric juice and bile salts), it was shown that the viability of probiotic cells in capsules was higher than that of free cells. This demonstrated the effectiveness of combining inulin and maltodextrin to encapsulate substances in surviving in gastro-intestinal conditions. Additionally, we evaluated the non-encapsulated and encapsulated SRBG1 by assessing their impact on the rheological parameters of fermented milk. The results showed that in the absence of sodium alginate the viscosity of milk was lower than with the other protectors, which was confirmed by the quick acidification of the fermented milk by microcapsules containing sodium alginate.

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