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1.
Ann Surg Oncol ; 29(13): 8583-8592, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36042101

RESUMO

BACKGROUND: Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) involves mixing oxaliplatin with 5% dextrose solution (5DW) to prevent the structural degradation of oxaliplatin in chloride-containing fluids. This study evaluated oxaliplatin degradation in carrier fluids containing different chloride ion concentrations to determine a carrier fluid that is optimal for use in oxaliplatin-based HIPEC. METHODS: Five types of carrier fluids (normal saline, half saline, 5DW, Dianeal PD-2 peritoneal dialysis solution, and non-chloride Dianeal solution) were compared. An in vitro study was performed that monitored an oxaliplatin concentration of 1 ml (2 mg/ml) oxaliplatin mixed in 24 ml of each carrier fluid during 3 days to evaluate the rate of oxaliplatin degradation in each carrier fluid. An in vivo study, which subjected Sprague-Dawley rats to HIPEC for 60 min, also was performed. The efficacy of each carrier fluid for preserving oxaliplatin was evaluated using area under the curve (AUC) ratios between peritoneal fluid and plasma. RESULTS: The degradation rate of oxaliplatin in non-chloride fluids was significantly lower than in chloride-containing fluids. However, the rate was less than 10 to 15% at 30 min. The in vivo study indicated that oxaliplatin concentrations in peritoneal fluids did not differ significantly, whereas those in plasma did differ. The AUC ratios of both normal saline and Dianeal were higher than those of 5DW and non-Cl- Dianeal solutions. CONCLUSIONS: Chloride-containing fluids, such as normal saline or Dianeal, which display high absorption rates of oxaliplatin and acceptable degradation rates, may be more beneficial for use in oxaliplatin-based HIPEC than 5DW.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Ratos , Animais , Oxaliplatina/uso terapêutico , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/tratamento farmacológico , Cloretos , Solução Salina/uso terapêutico , Ratos Sprague-Dawley , Neoplasias Colorretais/tratamento farmacológico , Antineoplásicos/uso terapêutico
2.
Molecules ; 27(3)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35164305

RESUMO

PURPOSE: Most therapeutic agents have limitations owing to low selectivity and poor solubility, resulting in post-treatment side effects. Therefore, there is a need to improve solubility and develop new formulations to deliver therapeutic agents specifically to the target site. Gelatin is a natural protein that is composed of several amino acids. Previous studies revealed that gelatin contains arginyl-glycyl-aspartic acid (RGD) sequences that become ligands for the integrin receptors expressed on cancer cells. Thus, in this study, we aimed to increase the efficiency of drug delivery into cancer cells by coating drug-encapsulating liposomes with gelatin (gelatin-coated liposomes, GCLs). METHODS: Liposomes were coated with gelatin using electrostatic interaction and covalent bonding. GCLs were compared with PEGylated liposomes in terms of their size, zeta potential, encapsulation efficiency, stability, dissolution profile, and cell uptake. Results: Small-sized and physically stable GCLs were prepared, and they showed high drug-encapsulation efficiency. An in vitro dissolution study showed sustained release depending on the degree of gelatin coating. Cell uptake studies showed that GCLs were superior to PEGylated liposomes in terms of cancer cell-targeting ability. CONCLUSIONS: GCLs can be a novel and promising carrier system for targeted anticancer agent delivery. GCLs, which exhibited various characteristics depending on the coating degree, could be utilized in various ways in future studies.


Assuntos
Antineoplásicos/administração & dosagem , Gelatina/química , Lipossomos/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Liberação Controlada de Fármacos , Células HeLa , Humanos , Polietilenoglicóis/química , Solubilidade
3.
Molecules ; 26(9)2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33925340

RESUMO

Rice bran arabinoxylan compound (RBAC) is derived from defatted rice bran hydrolyzed with Lentinus edodes mycelial enzyme. It has been marketed as a functional food and a nutraceutical with health-promoting properties. Some research has demonstrated this rice bran derivative to be a potent immunomodulator, which also possesses anti-inflammatory, antioxidant, and anti-angiogenic properties. To date, research on RBAC has predominantly focused on its immunomodulatory action and application as a complementary therapy for cancer. Nonetheless, the clinical applications of RBAC can extend beyond cancer therapy. This article is a narrative review of the research on the potential benefits of RBAC for cancer and other health conditions based on the available literature. RBAC research has shown it to be useful as a complementary treatment for cancer and human immunodeficiency virus infection. It can positively modulate serum glucose, lipid and protein metabolism in diabetic patients. Additionally, RBAC has been shown to ameliorate irritable bowel syndrome and protect against liver injury caused by hepatitis or nonalcoholic fatty liver disease. It can potentially ease symptoms in chronic fatigue syndrome and prevent the common cold. RBAC is safe to consume and has no known side effects at the typical dosage of 2-3 g/day. Nevertheless, further research in both basic studies and human clinical trials are required to investigate the clinical applications, mechanisms, and effects of RBAC.


Assuntos
Oryza/química , Óleo de Farelo de Arroz/química , Cogumelos Shiitake/enzimologia , Xilanos/química , Enzimas/química , Humanos , Óleo de Farelo de Arroz/uso terapêutico , Xilanos/uso terapêutico
4.
Ann Surg Oncol ; 25(11): 3185-3192, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30027459

RESUMO

BACKGROUND: Carrier solutions play an important role in the distribution, plasma absorption, chemical stability, and solubility of anticancer agents during hyperthermic intraperitoneal chemotherapy (HIPEC). In the current study, lipophilic properties of carrier solutions were evaluated to determine whether they improved anticancer drug absorption rates using mitomycin-C (MMC) or oxaliplatin HIPEC as compared to hydrophilic carrier solutions. METHODS: Sprague-Dawley rats were divided into two groups: MMC and oxaliplatin treatment groups. Each group was then further subdivided by carrier solution: Dianeal® PD-2 peritoneal dialysis solution, 5% dextrose solution and 20% lipid solution (Lipision®). HIPEC was performed over 60 min at 41-42 °C using the anticancer drugs MMC (35 mg/m2) or oxaliplatin (460 mg/m2). The plasma area under the curve (AUC; AUCplasma), peritoneal AUC (AUCperitoneum), and peritoneal/plasma AUC ratios were compared among HIPEC carrier solutions. RESULTS: Plasma drug concentrations were significantly different among carrier solutions, varying by time. In contrast, peritoneal drug concentrations did not change with carrier solution. In the MMC group, the peritoneal/plasma AUC ratio of a lipid solution was three times higher than Dianeal® (p < 0.001). In the oxaliplatin group, the peritoneal/plasma AUC ratio was significantly different between carrier solutions (p = 0.046). Although the oxaliplatin AUCperitoneum did not vary (p = 0.941), the AUCplasma of a lipid solution was lower than that of 5% dextrose solution (p = 0.039). CONCLUSIONS: The lipid carrier solution increases the peritoneal/plasma AUC ratio and decreases plasma absorption rates. However, further study is required before clinical uses, considering its pharmacologic properties and possible risks after HIPEC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hipertermia Induzida , Lipídeos/química , Neoplasias Peritoneais/terapia , Água/química , Animais , Lipídeos/análise , Masculino , Mitomicina/administração & dosagem , Oxaliplatina/administração & dosagem , Neoplasias Peritoneais/patologia , Ratos , Ratos Sprague-Dawley , Água/análise
7.
Molecules ; 22(12)2017 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-29236057

RESUMO

Houttuynia cordata (H. cordata) has been used for diuresis and detoxification in folk medicine as well as a herbal medicine with antiviral and antibacterial activities. H. cordata extract-loaded solid lipid nanoparticles (H-SLNs) were prepared with various concentration of poloxamer 188 or poloxamer 407 by a hot homogenization and ultrasonication method. H-SLNs dispersion was freeze-dried with or without trehalose as a cryoprotectant. The physicochemical characteristics of H-SLNs were evaluated by dynamic laser scattering (DLS), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). Additionally, the in vitro release and in vitro cytotoxicity of H-SLNs were measured. Encapsulation efficiencies of H-SLNs (as quercitrin) were 92.9-95.9%. The SEM images of H-SLNs showed that H-SLNs have a spherical morphology. DSC and FT-IR showed that there were no interactions between ingredients. The increased extent of particle size of freeze-dried H-SLNs with trehalose was significantly lower than that of H-SLNs without trehalose. H-SLNs provided sustained release of quercitrin from H. cordata extracts. Cell viability of Caco-2 cells was over 70% according to the concentration of various formulation. Therefore, it was suggested that SLNs could be good carrier for administering H. cordata extracts.


Assuntos
Preparações de Ação Retardada/química , Composição de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Houttuynia/química , Nanopartículas/química , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Crioprotetores/química , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Congelamento , Humanos , Cinética , Nanopartículas/ultraestrutura , Tamanho da Partícula , Poloxâmero/química , Quercetina/análogos & derivados , Quercetina/metabolismo , Quercetina/farmacologia , Sonicação , Ácidos Esteáricos/química , Trealose/química
8.
Int J Mol Sci ; 16(7): 16655-68, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26204837

RESUMO

Fluoxetine was originally developed as an antidepressant, but it has also been used to treat obesity. Although the anti-appetite effect of fluoxetine is well-documented, its potential effects on human adipose-derived stem cells (ASCs) or mature adipocytes have not been investigated. Therefore, we investigated the mechanisms underlying the inhibitory effects of fluoxetine on the proliferation of ASCs. We also investigated its inhibitory effect on adipogenic differentiation. Fluoxetine significantly decreased ASC proliferation, and signal transduction PCR array analysis showed that it increased expression of autophagy-related genes. In addition, fluoxetine up-regulated SQSTM1 and LC3B protein expression as detected by western blotting and immunofluorescence. The autophagy inhibitor, 3-methyladenine (3-MA), significantly attenuated fluoxetine-mediated effects on ASC proliferation and SQSTM1/LC3B expression. In addition, 3-MA decreased the mRNA expression of two autophagy-related genes, beclin-1 and Atg7, in ASCs. Fluoxetine also significantly inhibited lipid accumulation and down-regulated the levels of PPAR-γ and C/EBP-α in ASCs. Collectively, these results indicate that fluoxetine decreases ASC proliferation and adipogenic differentiation. This is the first in vitro evidence that fluoxetine can reduce fat accumulation by inhibiting ASC proliferation and differentiation.


Assuntos
Adipogenia , Proliferação de Células , Fluoxetina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Tecido Adiposo/citologia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia , Proteína 7 Relacionada à Autofagia , Proteína Beclina-1 , Células Cultivadas , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteína Sequestossoma-1 , Transdução de Sinais , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismo
9.
Molecules ; 20(6): 9496-509, 2015 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-26020699

RESUMO

The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD) on the degradation of sirolimus in simulated gastric fluid (pH 1.2) and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1) solid dispersion had a maximum solubility of 196.7 µg/mL within 0.5 h that gradually decreased to 173.4 µg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1) solid dispersion in simulated gastric fluid (pH 1.2), owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1) solid dispersion, the sirolimus/E-SD/TPGS (1/8/1) solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC). Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.


Assuntos
Materiais Biomiméticos/química , Portadores de Fármacos , Absorção pela Mucosa Oral/efeitos dos fármacos , Sirolimo/farmacocinética , Animais , Disponibilidade Biológica , Estabilidade de Medicamentos , Excipientes , Suco Gástrico/química , Concentração de Íons de Hidrogênio , Hidrólise/efeitos dos fármacos , Derivados da Hipromelose/química , Derivados da Hipromelose/farmacologia , Masculino , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacologia , Ratos , Ratos Sprague-Dawley , Sirolimo/química , Sirolimo/metabolismo , Solubilidade , Vitamina E/análogos & derivados , Vitamina E/química , Vitamina E/farmacologia
10.
Chem Pharm Bull (Tokyo) ; 62(6): 545-51, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24881660

RESUMO

The aim of the present study was to investigate the effect of Soluplus® on the solubility of atorvastatin calcium and to develop a solid dispersion formulation that can improve the oral bioavailability of atorvastatin calcium. We demonstrated that Soluplus® increases the aqueous solubility of atorvastatin calcium. Several solid dispersion formulations of atorvastatin calcium with Soluplus® were prepared at various drug : carrier ratios by spray drying. Physicochemical analysis demonstrated that atorvastatin calcium is amorphous in each solid dispersion, and the 2 : 8 drug : carrier ratio provided the highest degree of sustained atorvastatin supersaturation. Pharmacokinetic analysis in rats revealed that the 2 : 8 dispersion significantly improved the oral bioavailability of atorvastatin. This study demonstrates that spray-dried Soluplus® solid dispersions can be an effective method for achieving higher atorvastatin plasma levels.


Assuntos
Dessecação , Ácidos Heptanoicos/química , Ácidos Heptanoicos/farmacocinética , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polivinil/química , Polivinil/farmacologia , Pirróis/química , Pirróis/farmacocinética , Administração Oral , Animais , Atorvastatina , Disponibilidade Biológica , Ácidos Heptanoicos/administração & dosagem , Ácidos Heptanoicos/sangue , Masculino , Pirróis/administração & dosagem , Pirróis/sangue , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos , Água/química
11.
Int J Pharm ; 657: 124048, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537925

RESUMO

Doxorubicin hydrochloride (DOX) is an anticancer agent used in cancer chemotherapy. The purpose of this study was to design nanostructured lipid carriers (NLCs) of DOX as smart chemotherapy to improve its photostability and anticancer efficacy. The characteristics of DOX and DOX-loaded NLCs were investigated using UV-Vis spectroscopy, Fourier transform infrared (FTIR) spectroscopy, particle size, and zeta potential study. The cytotoxicity of DOX was evaluated against three cancer cell lines (HeLa, A549, and CT-26). The particle size and zeta potential were in the range 58.45-94.08 nm and -5.80 mV - -18.27 mV, respectively. The chemical interactions, particularly hydrogen bonding and van der Waals forces, between DOX and the main components of NLCs was confirmed by FTIR. NLCs showed the sustained release profile of DOX. The photostability results revealed that the NLC system improved the photostability of DOX. Cytotoxicity results using the three cell lines showed that all formulations improved the anticancer efficacy of free DOX, and the efficacy was dependent on cell type and particle size. These results suggest that DOX-loaded NLCs are promising chemotherapeutic agents for cancer treatment.


Assuntos
Sobrevivência Celular , Doxorrubicina , Portadores de Fármacos , Liberação Controlada de Fármacos , Lipídeos , Nanopartículas , Tamanho da Partícula , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Portadores de Fármacos/química , Nanopartículas/química , Lipídeos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Nanoestruturas/química , Estabilidade de Medicamentos , Células HeLa , Células A549 , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia
12.
Int J Pharm ; 661: 124386, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942182

RESUMO

Postoperative tissue adhesion is a well-recognized and common complication. Despite ongoing developments in anti-adhesion agents, complete prevention remains a challenge in clinical practice. Colorectal cancer necessitates both adhesion prevention and postoperative chemotherapy. Accordingly, drug-loading into an anti-adhesion agent could be employed as a treatment strategy to maximize the drug effects through local application and minimize side effects. Herein, we introduce an anti-adhesion agent that functions as a drug delivery system by loading drugs within an emulsion that forms a gel matrix in the presence of polysaccharides, xanthan gum, and pectin. Based on the rheological analysis, the xanthan gum-containing emulsion gel formed a gel matrix with suitable strength and mucosal adhesiveness. In vitro dissolution tests demonstrated sustained drug release over 12 h, while in vivo pharmacokinetic studies revealed a significant increase in the Tmax (up to 4.03 times) and area under the curve (up to 2.62 times). However, most of the drug was released within one day, distributing systemically and raising toxicity concerns, thus limiting its efficacy as a controlled drug delivery system. According to in vivo anti-adhesion efficacy evaluations, the xanthan gum/pectin emulsion gels, particularly F2 and F3, exhibited remarkable anti-adhesion capacity (P < 0.01). The emulsion gel formulation exhibited no cytotoxicity against fibroblasts or epithelial cell lines. Thus, the xanthan gum/pectin emulsion gel exhibits excellent anti-adhesion properties and could be developed as a drug delivery system.

13.
Cells ; 13(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38994939

RESUMO

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aß) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aß therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aß42), amyloid beta 40 (Aß40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aß42/Aß40, pTau181/Aß42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aß42/Aß40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aß42/Aß40 are potentially robust predictors of future AD conversion.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Biomarcadores , Disfunção Cognitiva , Proteínas tau , Humanos , Disfunção Cognitiva/sangue , Disfunção Cognitiva/diagnóstico , Biomarcadores/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Masculino , Feminino , Idoso , Estudos Longitudinais , Peptídeos beta-Amiloides/sangue , Proteínas tau/sangue , Pessoa de Meia-Idade , Progressão da Doença , Proteínas de Neurofilamentos/sangue , Proteína Glial Fibrilar Ácida/sangue , Estudos Prospectivos
14.
Pharmaceutics ; 15(3)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36986767

RESUMO

(1) Background: Solid dispersion (SD) can help increase the bioavailability of poorly water-soluble drugs. Meanwhile, apixaban (APX)-a new anticoagulation drug-has low water solubility (0.028 mg/mL) and low intestinal permeability (0.9 × 10-6 cm/s across Caco-2 colonic cells), thus resulting in a low oral bioavailability of <50%; (2) Methods: To solve the drawbacks of conventional APX products, a novel SD of APX in Soluplus® was prepared, characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopy techniques and evaluated for its solubility, intestinal permeability and pharmacokinetic performance. (3) Results: The crystallinity of the prepared APX SD was confirmed. The saturation solubility and apparent permeability coefficient increased 5.9 and 2.54 times compared to that of raw APX, respectively. After oral administration to the rats, the bioavailability of APX SD was improved by 2.31-fold compared to that of APX suspension (4) Conclusions: The present study introduced a new APX SD that potentially exhibits better solubility and permeability, thus increasing APX's bioavailability.

15.
Int J Pharm ; 646: 123426, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37729976

RESUMO

Delivering protein drugs through dry powder inhalation (DPI) remains a significant challenge. Liposomes offer a promising solution, providing protection for proteins from external environment and controlled release capabilities. Furthermore, the use of non-ionic surfactants plays a crucial role in protecting the activity of proteins because of how the surfactants positioning themselves at the liquid-gas interface during the spray-drying process. In this study, lysozyme-loaded liposomal DPI formulations were prepared using various non-ionic surfactants, including polysorbate 80, poloxamer 188, poloxamer 407, and sucrose stearate. Lysozyme solution and 1,2-distearoyl-sn-glycero-3-phosphatidylcholine liposomes were subjected through high-pressure homogenization to form lysozyme-loaded liposomes. Formulations of homogenized lysozyme liposomes were spray-dried and further characterized. The particle size of reconstituted liposomal lysozyme DPI was from 129.5 to 816.9 nm. The formulations showed encapsulation efficiency up to 32.5% with zeta potential value of around - 30 mV, and spherical structures were observed. The aerosol dispersion performance of the dry powder inhalers was evaluated with emitted doses reaching up to 103% and fine particle fractions up to 28.4%. Significantly higher lysozyme activity was confirmed in formulation with drug to PS 80 ratio of 1: 0.5 w/w (92.1%) compared to that of formulation containing no surfactant (59.8%). The formulation stood out as the only formulation that maintained protein activity while demonstrating good aerosol performance.

16.
Chem Pharm Bull (Tokyo) ; 60(4): 543-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22466739

RESUMO

The aims of this study were to identify how the solvent selection affects particle formation and to examine the effect of the initial drug solution concentration on mean particle size and particle size distribution in the supercritical antisolvent (SAS) process. Amorphous atorvastatin calcium was precipitated from seven different solvents using the SAS process. Particles with mean particle size ranging between 62.6 and 1493.7 nm were obtained by varying organic solvent type and solution concentration. By changing the solvent, we observed large variations in particle size and particle size distribution, accompanied by different particle morphologies. Particles obtained from acetone and tetrahydrofuran (THF) were compact and spherical fine particles, whereas those from N-methylpyrrolidone (NMP) and dimethylsulfoxide (DMSO) were agglomerated, with rough surfaces and relatively larger particle sizes. Interestingly, the mean particle size of atorvastatin calcium increased with an increase in the boiling point of the organic solvent used. Thus, for atorvastatin particle formation via the SAS process, particle size was determined mainly by evaporation of the organic solvent into the antisolvent phase. In addition, the mean particle size was increased with increasing drug solution concentration. In this study, from the aspects of particle size and solvent toxicity, acetone was the better organic solvent for controlling nanoparticle formation of atorvastatin calcium.


Assuntos
Ácidos Heptanoicos/química , Nanopartículas/química , Pirróis/química , Solventes/química , Acetona/química , Atorvastatina , Química Farmacêutica , Dimetil Sulfóxido/química , Furanos/química , Tamanho da Partícula , Pirrolidinonas/química
17.
Data Brief ; 42: 108137, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35496475

RESUMO

Zinc oxide (ZnO) nanoparticles (NPs) have been applied as high-performance intelligent materials to create a hierarchical multimodal-porous architectures for application in biomedical research fields [1]. They were microfluidically synthesized via dual-step nanofabrication compared to the conventional particles including ZnO NPs synthesized at single-pot macroscale, nanosized ZnO, and hybrid ZnO. The physicochemical properties were characterized, including morphology, particle size distribution, atomic composition, crystallinity, purity, reactant viscosity, surface charge, photocatalysis, photoluminescence, and porosity. A hierarchical multimodal-porous three-dimensional (3D) architecture of ZnO NPs was generated and optimized on the solid plate substrate of cellulose paper sheet after solvent evaporation. The dataset provides the nanomaterial design and architecture generation of ZnO NPs, explaining multi-physics phenomena in association with performance optimization processes.

18.
Pharmaceutics ; 14(8)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35893805

RESUMO

Significant improvements in the wettability and dissolution rate of celecoxib (CEL), a poorly soluble selective cyclooxygenase-2 (COX-2) inhibitor, have been shown by Huyn et al., 2019 by combining the binary pharmaceutical compositions including CEL and one of the two co-formers, adipic acid (ADI) and saccharin (SAC), into eutectic mixtures (EM). Purpose: In this study, we developed a therapeutic eutectic system for CEL which is a promising approach for oral delivery to enhance bioavailability. CEL EM were synthesized by novel techniques including supercritical CO2 techniques and new tablet formulations were purposed. Methods: CEL EM were synthesized by evaporation crystallization method, spray drying, supercritical fluid (SCF) techniques. The CEL EM particles were then characterized by differential scanning calorimetry, powder X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscope, and particle size analysis. Dissolution studies were carried out. With a quality by design approach, a statistical method through design of experiment and data analysis by JMP® (SAS institute) was applied to CEL EM immediate release tablet formulation development. Results: CEL EM produced by spray drying technique, supercritical fluid (SCF) techniques were identified and characterized. The enhancement of dissolution was observed for SCF processed samples. The design space for CEL-ADI EM IR tablet and control limits for individual parameters were determined.

19.
Pharmaceutics ; 14(1)2022 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-35057101

RESUMO

Donepezil (DPZ) is generally administered orally to treat Alzheimer's disease (AD). However, oral administration can cause gastrointestinal side effects. Therefore, to enhance compliance, a new way to deliver DPZ from transdermal patch was developed. Ionic bonds were created by dissolving dicarboxylic acid and DPZ in ethanol, resulting in a stable ionic liquid (IL) state. The synthesized ILs were characterized by differential scanning calorimetry, optical microscope, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy. The DPZ ILs were then transformed to a suitable drug-in-adhesive patch for transdermal delivery of DPZ. The novel DPZ ILs patch inhibits crystallization of the IL, indicating coherent design. Moreover, DPZ ILs and DPZ IL patch formulations performed excellent skin permeability compared to that of the DPZ free-base patch in both in vitro and ex vivo skin permeability studies.

20.
Biomolecules ; 12(4)2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35454114

RESUMO

Cinnamomum cassia is a natural product found in plants that has been used as a folk remedy for inflammation. In this study, we investigated the mechanism underlying the anti-inflammatory and antioxidant properties of C. cassia extract (ECC) in lipopolysaccharide (LPS)-induced murine RAW 264.7 cells, in comparison with 4-hydroxycinnamaldehyde, a C. cassia extract component. ECC and 4-hydroxycinnamaldehyde inhibited the production of nitrite oxide in a dose-dependent manner and did not show any change in cellular toxicity when treated with the same dose as that used in the nitrite assay. Moreover, they attenuated ROS accumulation after lipopolysaccharide (LPS) stimulation. ECC and 4-hydroxycinnamaldehyde decreased the mRNA and protein expression levels of inflammatory mediators (iNOS and COX-2) and cytokines such as TNF and IL-6. We also found that ECC and 4-hydroxycinnamaldehyde mitigated the phosphorylation of ERK, JNK, and transcription factors, such as NF-κB and STAT3, suppressing NF-κB nuclear translocation in LPS-activated macrophages. In addition, administration of ECC in a Sprague Dawley rat model of acute gastric injury caused by indomethacin significantly increased the gastric mucus volume. Analysis of serum and tissue levels of inflammatory mediators revealed a significant decrease in serum PGE2 and myeloperoxidase levels and a reduction in gastric iNOS, COX-2, and p65 protein levels. Collectively, these results suggest that ECC has antioxidant and anti-inflammatory effects and is a potential candidate for curing gastritis.


Assuntos
Cinnamomum aromaticum , Mucosa Gástrica , Extratos Vegetais , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cinnamomum aromaticum/química , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/lesões , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
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