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1.
Carbohydr Polym ; 330: 121817, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38368099

RESUMO

The development of oral film with diverse colors and customized nutrition is in line with the innovation of emerging food. In this study, polychromatic system was formed by regulating the ratio of phycocyanin (PC) to blueberry anthocyanin (BA). Further, chondroitin sulfate (CS) was utilized to achieve color-enhanced and homeostatic effects on PC-BA, and κ-carrageenan (KC) - starch complex was exploited as printing ink to construct oral film system. The color-enhanced effect of CS is mainly related to the complexation of sulfate groups, and the film-forming substrates are combined mainly through hydrogen bonding. In addition, the proportion of KC modulated the gel structure of printing ink, and affected 3D printability and physical properties of oral film. OF II (1.5 % KC content) had a uniform and dense network structure, with the most stable color and the highest BA retention (70.33 %) after 8 d of light exposure. Importantly, OF II had an excellent slow-release effect, and BA release rate was as high as 92.52 %. The optimized components can form polychromatic oral film with controllable color and structure, and provide new insights for the creation of sensory personalized and nutritionally customized food.


Assuntos
Antocianinas , Sulfatos de Condroitina , Carragenina , Ficocianina , Amido , Excipientes , Homeostase , Impressão Tridimensional
2.
Pharm Biol ; 62(1): 183-194, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38351624

RESUMO

CONTEXT: The therapeutic potential of andrographolide is hindered by its poor oral bioavailability and unpredictable pharmacokinetics, primarily due to its limited water solubility. OBJECTIVE: This work aimed to enhance the solubility and pharmacokinetics of andrographolide, a bioactive compound in Andrographis paniculata (Burm. f.) Nees (Acanthaceae), using solubilizing agents and a bioenhancer. MATERIALS AND METHODS: Four groups of beagles were compared: (1) A. paniculata powder alone (control), (2) A. paniculata powder with 50% weight/weight (w/w) ß-cyclodextrin solubilizer, (3) A. paniculata powder with 1% w/w sodium dodecyl sulfate (SDS) solubilizer, and (4) A. paniculata powder co-administered with 1% w/w SDS solubilizer and 10% piperine bioenhancer. All groups received a consistent oral dose of 3 mg/kg of andrographolide, administered both as a single dose and multiple doses over seven consecutive days. RESULTS: Thirteen chemical compounds were identified in A. paniculata powder, including 7 diterpenoids, 5 flavonoids, and 1 phenolic compound. A. paniculata co-administration with either 50% w/w ß-cyclodextrin or 1% w/w SDS, alone or in combination with 10% w/w piperine, significantly increased systemic andrographolide exposure by enhancing bioavailability (131.01% to 196.05%) following single and multiple oral co-administration. Glucuronidation is one possible biotransformation pathway for andrographolide, as evidenced by the excretion of glucuronide conjugates in urine and feces. CONCLUSION: The combination of solubilizing agents and a bioenhancer improved the oral bioavailability and pharmacokinetics of andrographolide, indicating potential implications for A. paniculata formulations and clinical therapeutic benefits. Further investigation in clinical studies is warranted.


Assuntos
Alcaloides , Andrographis , Benzodioxóis , Diterpenos , Piperidinas , Alcamidas Poli-Insaturadas , beta-Ciclodextrinas , Animais , Cães , Andrographis paniculata , Disponibilidade Biológica , Pós , Andrographis/química , Extratos Vegetais , Excipientes
3.
AAPS J ; 26(1): 25, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355847

RESUMO

Degradation of therapeutic monoclonal antibodies (mAbs) is a major concern as it affects efficacy, shelf-life, and safety of the product. Taurine, a naturally occurring amino acid, is investigated in this study as a potential mAb stabilizer with an extensive analytical characterization to monitor product degradation. Forced degradation of trastuzumab biosimilar (mAb1)-containing samples by thermal stress for 30 min resulted in high-molecular-weight species by more than 65% in sample without taurine compared to the sample with taurine. Samples containing mAb1 without taurine also resulted in higher Z-average diameter, altered protein structure, higher hydrophobicity, and lower melting temperature compared to samples with taurine. The stabilizing effect of taurine was retained at different mAb and taurine concentrations, time, temperatures, and buffers, and at the presence of polysorbate 80 (PS80). Even the lowest taurine concentration (10 mM) considered in this study, which is in the range of taurine levels in amino acid injections, resulted in enhanced mAb stability. Taurine-containing samples resulted in 90% less hemolysis than samples containing PS80. Additionally, mAb in the presence of taurine showed enhanced stability upon subjecting to stress with light of 365 nm wavelength, combination of light and H2O2, and combination of Fe2+ and H2O2, as samples containing mAb without taurine resulted in increased degradation products by more than 50% compared to samples with taurine upon subjecting to these stresses for 60 min. In conclusion, the presence of taurine enhanced physical stability of mAb by preventing aggregate formation, and the industry can consider it as a new mAb stabilizer.


Assuntos
Anticorpos Monoclonais , Taurina , Anticorpos Monoclonais/química , Peróxido de Hidrogênio , Trastuzumab , Polissorbatos/química , Excipientes , Aminoácidos
4.
AAPS PharmSciTech ; 25(2): 34, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332233

RESUMO

Pravastatin sodium (PVS) is a hypolipidemic drug with poor oral bioavailability due to the first-pass effect. Therefore, this study aims to formulate and evaluate transdermal patches containing PVS-loaded nanoemulsions (PVS-NEs) to increase PVS's hypolipidemic and hepatoprotective activities. PVS-NEs were prepared using the aqueous titration method, where oleic acid was chosen as an oil phase, and span 80 and tween 80 were used as surfactant and cosurfactant respectively. Droplet size (DS), polydispersity index (PDI), zeta potential (ZP), clarity, and thermodynamic stability of NEs were all characterized. Also, PVS-NEs (NE2) with 50% oil phase, 40% SC mix 2:1, and 10% water were selected as an optimum formula based on the results of DS (251 ± 16), PDI (0.4 ± 0.16), and ZP (-70 ± 10.4) to be incorporated into a transdermal patch, and PVS-NE2 loaded transdermal patches (PVS-NE2-TDPs) were prepared by solvent evaporation method. F1 patch with HPMC E15 and PVP K30 in a ratio of 3:1 represented satisfactory patch properties with good drug-excipients compatibility. Thus, it was selected as an optimum patch formula. The optimized F1 patch was characterized for thickness, moisture content, weight variation, and drug-excipients incompatibility. Therefore, it was subjected to ex vivo skin permeation and finally pharmacodynamic studies. Ex vivo permeation studies of F1 revealed that the cumulative amount of PVS permeated across rat skin was 271.66 ± 19 µg/cm2 in 72 h, and the pharmacodynamic studies demonstrated that the F1 patch was more effective in treating hyperlipidemia than PVS-TDP (control patch) based on both blood analysis and histopathological examination. .


Assuntos
Hiperlipidemias , Pravastatina , Ratos , Animais , Administração Cutânea , Excipientes , Adesivo Transdérmico , Hiperlipidemias/tratamento farmacológico , Ratos Wistar
5.
AAPS PharmSciTech ; 25(2): 32, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332361

RESUMO

Bacterial cellulose (BC) is an interesting material for drug delivery applications due to its high purity. This study aimed to compare the properties of tablets prepared by the wet granulation method using bacterial cellulose prepared by different methods as a diluent, using acetaminophen as a model drug. BC used as diluents were prepared using two different methods: freeze-drying (BC-FD) and phase-inversion (BC-PI), and their characteristics were analyzed and compared with that of commercial microcrystalline cellulose PH 101 (Comprecel® M101). Acetaminophen tablets were prepared by wet granulation using BC-FD, BC-PI, or Comprecel® M101 as diluents, and their tablet properties were examined. The result showed that the morphology, polymorph, and crystallinity of BC-PI and Comprecel® M101 were similar but they were different compared with that of BC-FD. Tablets could be successfully formed using BC-PI and Comprecel® M101 as diluents without any physical defects but the tablet prepared using BC-FD as diluent appeared chipped edge. The characteristics (thickness, weight variation, hardness, friability, disintegration, drug content, and dissolution) of the tablets prepared using BC-PI diluent were also similar to those prepared using Comprecel® M101 diluent, but those of BC-FD diluent were inferior. This indicates that BC prepared in BC-PI can potentially be used as a diluent for tablets prepared by wet granulation.


Assuntos
Acetaminofen , Celulose , Acetaminofen/química , Celulose/química , Solubilidade , Excipientes/química , Comprimidos/química
6.
AAPS PharmSciTech ; 25(2): 36, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38356031

RESUMO

Pulmonary drug delivery is a form of local targeting to the lungs in patients with respiratory disorders like cystic fibrosis, pulmonary arterial hypertension (PAH), asthma, chronic pulmonary infections, and lung cancer. In addition, noninvasive pulmonary delivery also presents an attractive alternative to systemically administered therapeutics, not only for localized respiratory disorders but also for systemic absorption. Pulmonary delivery offers the advantages of a relatively low dose, low incidence of systemic side effects, and rapid onset of action for some drugs compared to other systemic administration routes. While promising, inhaled delivery of therapeutics is often complex owing to factors encompassing mechanical barriers, chemical barriers, selection of inhalation device, and limited choice of dosage form excipients. There are very few excipients that are approved by the FDA for use in developing inhaled drug products. Depending upon the dosage form, and inhalation devices such as pMDIs, DPIs, and nebulizers, different excipients can be used to provide physical and chemical stability and to deliver the dose efficiently to the lungs. This review article focuses on discussing a variety of excipients that have been used in novel inhaled dosage forms as well as inhalation devices.


Assuntos
Asma , Excipientes , Humanos , Excipientes/farmacologia , Administração por Inalação , Nebulizadores e Vaporizadores , Asma/tratamento farmacológico , Pulmão , Preparações Farmacêuticas
7.
Sci Rep ; 14(1): 935, 2024 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-38195769

RESUMO

In this study, a ZnO/MnO nanocomposite was myco-fabricated using the isolated endophytic Clonostachys rosea strain EG99 as the nano-factory. The extract of strain EG99, a reducing/capping agent, was successfully titrated with equal quantities of Zn(NO3)2·6H2O and Mn(NO3)2·6H2O (precursors) in a single step to fabricate the rod-shaped ZnO/MnO nanocomposite of size 6.22 nm. The ZnO/MnO nanocomposite was myco-fabricated in 20 min, and the results were validated at 350 and 400 nm using UV-Vis spectroscopy. In a 7-L bioreactor, an industrial biotechnological approach was used to scale up the biomass of this strain, EG99, and the yield of the myco-fabricated ZnO/MnO nanocomposite. A controlled fed-batch fermentation system with a specific nitrogen/carbon ratio and an identical feeding schedule was used in this production process. Higher yields were obtained by adopting a controlled fed-batch fermentation approach in a 7-L bioreactor with a regular feeding schedule using a nitrogen/carbon ratio of 1:200. Overall, the fed-batch produced 89.2 g/l of biomass at its maximum, 2.44 times more than the batch's 36.51 g/l output. Furthermore, the fed-batch's maximum ZnO/MnO nanocomposite yield was 79.81 g/l, a noteworthy 14.5-fold increase over the batch's yield of 5.52 g/l. Finally, we designed an innovative approach to manage the growth of the endophytic strain EG99 using a controlled fed-batch fermentation mode, supporting the rapid, cheap and eco-friendly myco-fabrication of ZnO/MnO nanocomposite. At a dose of 210 µg/ml, the tested myco-fabricated ZnO/MnO nanocomposite exhibited the maximum antibacterial activity against Staphylococcus aureus (98.31 ± 0.8%), Escherichia coli (96.70 ± 3.29%), and Candida albicans (95.72 ± 0.95%). At the same dose, Staphylococcus aureus biofilm was eradicated in 48 h; however, Escherichia coli and Candida albicans biofilms needed 72 and 96 h, respectively. Our myco-fabricated ZnO/MnO nanocomposite showed strong and highly selective antagonistic effects against a variety of multidrug-resistant human pathogens. Therefore, in upcoming generations of antibiotics, it might be employed as a nano-antibiotic.


Assuntos
Anti-Infecciosos , Óxido de Zinco , Humanos , Óxido de Zinco/farmacologia , Antibacterianos/farmacologia , Candida albicans , Carbono , Escherichia coli , Excipientes , Nitrogênio
8.
Orphanet J Rare Dis ; 19(1): 12, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183105

RESUMO

BACKGROUND: Hereditary fructose intolerance (HFI) is a rare metabolic disease caused by aldolase B deficiency. The aim of our study was to analyse excipient tolerability in patients with HFI and other related diseases and to design mobile and website health applications to facilitate the search for drugs according to their tolerance. RESULTS: A total of 555 excipients listed in the Spanish Medicines Agency database (July 2023) were classified as suitable for HFI patients, suitable with considerations ((glucose and glucose syrup, intravenous sucrose, oral mannitol, polydextrose, gums and carrageenans, ethanol, sulfite caramel and vanilla), not recommended (intravenous mannitol) and contraindicated (fructose, oral sucrose, invert sugar, sorbitol, maltitol, lactitol, isomaltitol, fruit syrups, honey, sucrose esters and sorbitol esters). Glucose and glucose syrup were classified as suitable with considerations due to its possible fructose content and their potential endogenous fructose production. For other related intolerances, wheat starch was contraindicated and oatmeal was not recommended in celiac disease; oral lactose and lactose-based coprocessed excipient (Cellactose®) were not recommended in lactose intolerance; and glucose, invert sugar and oral sucrose were not recommended in diabetes mellitus. The applications were named IntoMed®. Results are listed in order of tolerability (suitable drugs appear first and contraindicated drugs at the end), and they are accompanied by a note detailing their classified excipients. If a drug contains excipients within different categories, the overall classification will be the most restrictive. The apps are also able to classify substances with the same criteria if they act as active ingredients. The tools exhibited good usability (82.07 ± 13.46 points on the System Usability Scale [range: 0-100]) on a sample of HFI patients, their families and health care professionals. CONCLUSIONS: IntoMed® is a tool for finding information about the tolerability of drugs according to excipients for patients with HFI and other related intolerances, with good usability. It is a fast and reliable system that covers the current excipient legislation and expands on it with other specific information: HFI patients should be alert for excipients such as mannitol (especially in intravenous drugs), fruit syrups, honey, sulfite caramel or vanilla. Glucose might contain or produce fructose, and special precaution is needed because of potential errors in their composition.


Assuntos
Intolerância à Frutose , Humanos , Excipientes , Lactose , Frutose , Manitol , Sorbitol , Glucose , Sacarose , Sulfitos
9.
Eur J Pharm Sci ; 194: 106704, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38228279

RESUMO

Microparticles have unique benefits in the formulation of multiparticulate and multi-unit type pharmaceutical dosage forms allowing improved drug safety and efficacy with favorable pharmacokinetics and patient centricity. On the other hand, the above advantages are served by high and well reproducible quality attributes of the medicinal product where even flexible design and controlled processability offer success as well as possible longer product life-cycle for the manufacturers. Moreover, the specific demands of patients can be taken into account, including simplified dosing regimens, flexible dosage, drug combinations, palatability, and ease of swallowing. In the more than 70 years since the first modified-release formulation appeared on the market, many new formulations have been marketed and many publications have appeared in the literature. More unique and newer pharmaceutical technologies and excipients have become available for producing tailor-made particles with micrometer dimensions and beyond. All these have contributed to the fact that the sub-units (e.g. minitablets, pellets, microspheres) that make up a multiparticulate system can vary widely in composition and properties. Some units have mucoadhesive properties and others can float to contribute to a suitable release profile that can be designed for the multiparticulate formula as a whole. Nowadays, there are some available formulations on the market, which are able to release the active substance even for several months (3 or 6 months depending on the type of treatment). In this review, the latest developments in technologies that have been used for a long time are presented, as well as innovative solutions such as the applicability of 3D printing to produce subunits of multiparticulate systems. Furthermore, the diversity of multiparticulate systems, different routes of administration are also presented, touching the ones which are capable of carrying the active substance as well as the relevant, commercially available multiparticle-based medical devices. The versatility in size from 1 µm and multiplicity of formulation technologies promise a solid foundation for the future applications of dosage form design and development.


Assuntos
Sistemas de Liberação de Medicamentos , Excipientes , Humanos , Preparações Farmacêuticas
10.
Molecules ; 29(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38202847

RESUMO

Arbidol hydrochloride is an antiviral product widely used in Russia and China for the treatment of, among other diseases, influenza. In recent years, it has turned out to be highly effective against COVID-19. However, there is little knowledge about its physicochemical properties and its behavior in the presence of various pharmaceutical excipients, which could be useful in the development of new preparations by increasing its solubility and bioavailability. For this reason, binary mixtures composed of arbidol hydrochloride and selected pharmaceutical excipients such as chitosan, polyvinylpyrrolione K-30 and magnesium stearate were prepared and subjected to differential scanning calorimetry (DSC), thermogravimetry combined with Fourier transform infrared spectrometry (TGA-FTIR) and Fourier transform infrared spectrometry (FTIR) analyses. In order to obtain clarity in the interpretation of the outcomes, chemometric calculations with factor analysis (FA) were used. Additionally, a powder X-ray diffraction (PXRD) and an intrinsic dissolution rate study were performed for arbidol hydrochloride itself and in the presence of excipients. As a result of the study, it was revealed that arbidol hydrochloride may undergo polymorphic transformations and be incompatible with chitosan and magnesium stearate. However, mixing arbidol hydrochloride with polyvinylpyrrolidone K-30 guarantees the obtaining of durable and safe pharmaceutical preparations.


Assuntos
Quimiometria , Quitosana , Indóis , Sulfetos , Varredura Diferencial de Calorimetria , Excipientes , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , Análise Fatorial , Ácido Clorídrico , Antivirais
11.
J Drugs Dermatol ; 23(1): 1355-1356, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206137

RESUMO

Post-hyaluronic acid filler nodules are uncommon, unpredictable complications that present a challenge to clinical therapy. We report a case of a female in her fifties who developed edema and nodules 6 weeks after hyaluronic acid (HA) filler injection. After minimal improvement with oral steroids and intralesional hyaluronidase, a trial of oral abrocitinib was initiated, which yielded significant clinical improvement. Thus, abrocitinib may be a novel therapeutic option for delayed-onset nodules following injection of hyaluronic acid. J Drugs Dermatol. 2024;23(1):1355-1356.   doi:10.36849/JDD.7271.


Assuntos
Excipientes , Ácido Hialurônico , Pirimidinas , Humanos , Feminino , Ácido Hialurônico/efeitos adversos , Hialuronoglucosaminidase , Sulfonamidas
12.
J Drugs Dermatol ; 23(1): 1247-1252, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206154

RESUMO

BACKGROUND: Hyaluronic acid (HA) fillers are among the most used fillers for soft-tissue augmentation. There are now many FDA-approved HA products, and the successful use of injectable HA fillers requires an understanding of the available options.  Objective: The purpose of this manuscript is to provide a comprehensive list of HA fillers and their indications. An overview of their biochemical properties and formulations will aid dermatologists in appropriate use. METHODS: A comprehensive search of all the FDA-approved dermal fillers was conducted via the FDA "pre-market approval" (PMA) site. Additional details regarding filler properties were obtained using the respective agent's package inserts.  Results: A total of 28 HA dermal fillers were identified and key pharmaceutical properties were discussed. These findings will help the physician match the appropriate HA filler with the area that is to be treated.  Conclusion: Understanding the available fillers and their properties can help physicians select the appropriate fillers for more predictable and sustainable results.  J Drugs Dermatol. 2024;23(1):1247-1252.    doi:10.36849/JDD.7858.


Assuntos
Preenchedores Dérmicos , Farmácia , Médicos , Estados Unidos , Humanos , Ácido Hialurônico , Excipientes
13.
J Drugs Dermatol ; 23(1): 1284-1291, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206155

RESUMO

BACKGROUND: Age-related loss of midfacial contour is frequently corrected using dermal fillers. A validated photonumeric scale is beneficial when evaluating post-treatment aesthetic improvement. OBJECTIVE: To present scale-development activities for the Merz Cheek Fullness Assessment Scale (MCFAS) and report pilot-study results of a hyaluronic-acid filler (Belotero Volume with Lidocaine; CPM-HA-V) to treat midfacial volume loss. METHODS: A 5-point photonumeric scale was developed to objectively assess midface volume loss. Rater reliability was evaluated using live assessments. The clinical relevance of a 1-point difference in severity grade was evaluated using photographic comparisons. Pilot-study participants, with moderate-to-severe volume loss on the MCFAS, were randomized 2:1 to treatment or untreated control. Effectiveness was evaluated using the MCFAS, and adverse events were recorded. RESULTS: The MCFAS demonstrated substantial intra- and interrater agreement among physicians (weighted kappa > 0.6). The mean absolute difference (95% confidence interval) in scale ratings was 1.12 (1.00, 1.24) for photographic pairs differing by one grade and was 0.55 (0.48, 0.63) for pairs of the same grade, suggesting a 1-point difference is clinically relevant. In the pilot study, significant  (P < 0.0001) differences were observed in MCFAS response rates between treatment and control. No safety concerns were identified. CONCLUSION: The MCFAS is a validated, reliable, and clinically relevant photonumeric scale for rating midfacial volume loss in males and females of various ages and skin types. In a pilot study, CPM-HA-V was found to be safe and tolerable, and the MCFAS was able to detect clinically meaningful post-treatment changes. J Drugs Dermatol. 2024;23(1):     doi:10.36849/JDD.7981.


Assuntos
Excipientes , Projetos de Pesquisa , Feminino , Masculino , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Estética
14.
J Drugs Dermatol ; 23(1): 1274-1277, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38206153

RESUMO

BACKGROUND: Keratosis pilaris (KP) is a benign dermatosis consisting of folliculocentric keratotic papules or pustules with surrounding erythema, often on proximal extensor surfaces of extremities. Management strategies for KP largely center on moisturization and exfoliation. Urea, a well-established ingredient in topical skincare, is a component of the natural moisturizing factors with concentration-dependent humectant, emollient, and exfoliative properties.  Given the overlap of urea’s properties and management goals of KP, a 4-week, open-label, noncomparative clinical study was conducted to evaluate a moisturizing cream formulated with 20% urea for use in KP.  Thirty participants aged 18 to 65 years with KP completed this study. After a 5-day washout period, study participants applied a 20% urea cream once daily to areas of KP for 4 weeks. At baseline, 1-week, and 4-week visits, clinical grading of skin texture, adverse event monitoring, and participant satisfaction questionnaires were conducted. After 1 week and 4 weeks of product use, the percent change in skin smoothness/texture from baseline was significant (P≤0.001). Furthermore, after 4 weeks of use, the majority of participants indicated satisfaction with the feel of their skin, as well as improved confidence and decreased embarrassment related to their skin. No significant adverse events were reported. Overall, the results of this study support that 20% urea cream is generally well tolerated and suitable for use in treating KP. J Drugs Dermatol. 2024;23(1):1274-1277.     doi:10.36849/JDD.7806.


Assuntos
Anormalidades Múltiplas , Doença de Darier , Sobrancelhas , Humanos , Emolientes , Emoções , Excipientes , Sobrancelhas/anormalidades , Pele
15.
J Chem Theory Comput ; 20(3): 1479-1488, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38294777

RESUMO

Protein-protein interactions lie at the center of many biological processes and are a challenge in formulating biological drugs, such as antibodies. A key to mitigating protein association is to use small-molecule additives, i.e., excipients that can weaken protein-protein interactions. Here, we develop a computationally efficient model for predicting the viscosity-reducing effect of different excipient molecules by combining atomic-resolution MD simulations, binding polynomials, and a thermodynamic perturbation theory. In a proof of principle, this method successfully ranks the order of four types of excipients known to reduce the viscosity of solutions of a particular monoclonal antibody. This approach appears useful for predicting the effects of excipients on protein association and phase separation, as well as the effects of buffers on protein solutions.


Assuntos
Anticorpos Monoclonais , Excipientes , Excipientes/química , Anticorpos Monoclonais/química , Viscosidade
16.
Analyst ; 149(4): 1061-1067, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38251754

RESUMO

Pharmaceutical polymers and excipients represent interesting but often overlooked chemical classes in clinical exposure and bioanalytical research. These chemicals may cause hypersensitivity reactions, they can be useful to confirm exposure to pharmaceuticals, and they may pose bioanalytical challenges, including ion suppression in liquid chromatography-mass spectrometry (LC-MS-)based workflows. In this work, we assessed these chemicals in light of a rather surprising finding presented in two previously published studies, namely that usage of cyclosporine A, an immunosuppressive drug which is known to be cleared through excretion in the bile, explained the largest amount of variance in principal component analysis of urinary LC-SWATH/MS small-molecule profiling data. Specifically, we examined the freely-accessible 24-hour urine metabolomics data of 570 kidney transplant recipients included in the TransplantLines Biobank and Cohort Study (NCT03272841). These data unveiled thousands of high-abundance polymer peaks in some samples, which were associated with the use of the macrogol (i.e., polyethylene glycol) 3350 oral laxative agent. In addition, we found multiple clusters of high-abundance peaks which were linked to the exposure to two pharmaceutical excipients, namely short-chain polyethylene glycol (molecular weight <1000 Da) and polyethoxylated castor oil (also known as Kolliphor® EL or Cremophor® EL). Respectively, these excipients are used in temazepam capsules and cyclosporine A capsules, and the latter provides a plausible explanation for the rather surprising finding that instigated our work. Moreover, such explanation and our findings in general put emphasis on taking into consideration these and other pharmaceutical polymers and excipients when exploring, processing, and interpreting clinical small-molecule profiling data.


Assuntos
Ciclosporina , Excipientes , Humanos , Excipientes/química , Polímeros , Estudos de Coortes , Polietilenoglicóis/química , Metabolômica/métodos
17.
Food Chem ; 442: 138404, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38237295

RESUMO

Aluminum is added to many food colors to change their solubility. This study compares the aluminum-containing food color carmine with its aluminum-free version carminic acid (both E 120), hypothesizing that the addition of aluminum does not only change the color's solubility, but also its effects on human cells. We could show that carmine, but not carminic acid, is taken up by gastrointestinal Caco-2 and umbilical vein endothelial cells (HUVEC). Clear differences between gene expression profiles of Caco-2 cells exposed to carmine, carminic acid or control were shown. KEGG analysis revealed that carmine-specific genes suppress oxidative phosphorylation, and showed that this suppression is associated with neurodegenerative diseases such as Alzheimer and Parkinson disease. Furthermore, carmine, but not carminic acid, increased proliferation of Caco-2 cells. Our findings show that a food color containing aluminum induces different cellular effects compared to its aluminum-free form, which is currently not considered in EU legislation.


Assuntos
Carmim , Corantes de Alimentos , Humanos , Carmim/análise , Alumínio/toxicidade , Células CACO-2 , Células Endoteliais , Corantes de Alimentos/análise , Excipientes
18.
Biomacromolecules ; 25(2): 1119-1132, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38252967

RESUMO

Hydrogels composed of natural polysaccharides have been widely used as filling materials, with a growing interest in medical cosmetology and skin care. However, conventional commercial dermal fillers still have limitations, particularly in terms of mechanical performance and durability in vivo. In this study, a novel injectable and implantable hydrogel with adjustable characteristics was prepared from succinoglycan riclin by introducing PEG diglycidyl ether as a cross-linker. FTIR spectra confirmed the cross-linking reaction. The riclin hydrogels exhibited shear-thinning behavior, excellent mechanical properties, and cytocompatibility through in vitro experiments. Furthermore, when compared with subcutaneous injection of a commercial hyaluronic acid hydrogel, the riclin hydrogels showed enhanced persistence and biocompatibility in Balb/c mice after 16 weeks. These results demonstrate the great potential of the riclin-based hydrogel as an alternative to conventional commercial soft tissue fillers.


Assuntos
Hidrogéis , Engenharia Tecidual , Animais , Camundongos , Injeções Subcutâneas , Ácido Hialurônico , Excipientes , Camundongos Endogâmicos BALB C , Polietilenoglicóis , Éteres
19.
Int J Mol Sci ; 25(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255957

RESUMO

In this work, we present the effect of graphene nanoplatelets (GnPs) modification with ionic liquids (ILs). The textural properties of graphene nanoplatelets (GnPs) used as styrene-butadiene rubber's filler and the thermal properties of the composites obtained with the use of the mentioned fillers were investigated. GnPs were modified with 1-butylpyridinium bromide (BPyBr) and 4-methyl-1-butylpyridinium bromide (BmPyBr) through two different ways. One strategy has been to deposit the filler modifier from the solution. The second one involved the modification of the filler with ionic liquids in bulk during the preparation of elastomer blends. Settlement of the proposed ionic liquids onto the GnPs' surface led to significant changes in the textural characteristics. BPyBr has restricted the filler's microporosity, whereas BmPyBr has caused the formation of a more opened filler structure without the increase in its average pore size. GnPs modified with ILs led to reducing the temperature of vulcanization of SBR compounds and affected the thermal stability of the composites.


Assuntos
Grafite , Hidrocarbonetos Bromados , Líquidos Iônicos , Brometos , Elastômeros , Excipientes
20.
Int J Mol Sci ; 25(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256226

RESUMO

Cell membrane chromatography (CMC) has been widely recognized as a highly efficient technique for in vitro screening of active compounds. Nevertheless, conventional CMC approaches suffer from a restricted repertoire of cell membrane proteins, making them susceptible to oversaturation. Moreover, the binding mechanism between silica gel and proteins primarily relies on intermolecular hydrogen bonding, which is inherently unstable and somewhat hampers the advancement of CMC. Consequently, this investigation aimed to establish a novel CMC column that could augment protein loading, enhance detection throughput, and bolster binding affinity through the introduction of covalent bonding with proteins. This study utilizes polydopamine (PDA)-coated silica gel, which is formed through the self-polymerization of dopamine (DA), as the carrier for the CMC column filler. The objective is to construct the HK-2/SiO2-PDA/CMC model to screen potential therapeutic drugs for gout. To compare the quantity and characteristics of Human Kidney-2 (HK-2) cell membrane proteins immobilized on SiO2-PDA and silica gel, the proteins were immobilized on both surfaces. The results indicate that SiO2-PDA has a notably greater affinity for membrane proteins compared to silica gel, resulting in a significant improvement in detection efficiency. Furthermore, a screening method utilizing HK-2/SiO2-PDA/CMC was utilized to identify seven potential anti-gout compounds derived from Plantago asiatica L. (PAL). The effectiveness of these compounds was further validated using an in vitro cell model of uric acid (UA) reabsorption. In conclusion, this study successfully developed and implemented a novel CMC filler, which has practical implications in the field.


Assuntos
Gota , Indóis , Plantago , Polímeros , Humanos , Sílica Gel , Dióxido de Silício , Membrana Celular , Proteínas de Membrana , Rim , Cromatografia , Excipientes
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