RESUMO
Gold-based nanoparticles hold promise as functional nanomedicines, including in combination with a photothermal effect for cancer therapy in conjunction with chemotherapy. Here, we synthesized hollow gold nanoparticles (HGNPs) exhibiting efficient light absorption in the near-IR (NIR) region. Several synthesis conditions were explored and provided monodisperse HGNPs approximately 95-135 nm in diameter with a light absorbance range of approximately 600-720 nm. The HGNPs were hollow and the surface had protruding structures when prepared using high concentrations of HAuCl4. The simultaneous nucleation of a sacrificial AgCl template and Au nanoparticles may affect the resulting HGNPs. Diethyldithiocarbamate (DDTC) is metabolized from disulfiram and is a repurposed drug currently attracting attention. The chelation of DDTC with copper ion (DDTC-Cu) has been investigated for treating glioma, and here we confirmed the cytotoxic effect of DDTC-Cu towards rat C6 glioma cells in vitro. HGNPs alone were biocompatible and showed little cytotoxicity, whereas a mixture of DDTC-Cu and HGNPs was cytotoxic in a dose dependent manner. The temperature of HGNPs was increased by NIR-laser irradiation. The photothermal effect on HGNPs under NIR-laser irradiation resulted in cytotoxicity towards C6 cells and was dependent on the irradiation time. Photothermal therapy by HGNPs combined and DDTC-Cu was highly effective, suggesting that this combination approach hold promise as a future glioma therapy.
Assuntos
Antineoplásicos , Glioma , Nanopartículas Metálicas , Animais , Ratos , Ditiocarb/farmacologia , Cobre , Ouro , Terapia Fototérmica , Antineoplásicos/farmacologia , Linhagem Celular , Glioma/tratamento farmacológicoRESUMO
Hospital-acquired pneumonia is an important infectious disease that requires special management and therapy for patients with compromised immunity, as opportunistic infections with microorganisms such as Pseudomonas aeruginosa can be fatal. Nanoparticle-based drug delivery to lung tissue provides several advantages in the treatment of respiratory diseases. In the current study, inhalable nanocomposite particles consisting of microparticles containing solid-state arbekacin (ABK) nanoparticles coated with hydrophobic surfactant (ABK-SD nanoparticles) were prepared using a spray dryer equipped with a two-solution mixing-type spray nozzle we previously developed. ABK-SD/mannitol (MAN) nanocomposite particles were obtained from ABK-SD nanoparticles by varying the amounts of hydrophobic surfactant and ABK. The aerosol performance of ABK-SD/MAN nanocomposite particles was superior to that of ABK-MAN microparticles in terms of the fine particle fraction (28.4 ± 5.4%, ABK-SD/MAN nanocomposite particles; 11.4 ± 7.6%, ABK-MAN microparticles). These results suggest that ABK-SD/MAN nanocomposite particles are suitable for use in inhalation drug formulations and useful for the treatment of lung infections involving Pseudomonas aeruginosa.
Assuntos
Nanocompostos , Nanopartículas , Humanos , Pseudomonas aeruginosa , Composição de Medicamentos/métodos , Administração por Inalação , Nanocompostos/química , Nanopartículas/química , Tensoativos , Manitol , Tamanho da PartículaRESUMO
Since three-dimensional (3D)-printed tablets were approved by the United States Food and Drug Administration (FDA), 3D printing technology has garnered increasing interest for the fabrication of medical and pharmaceutical devices. With various dosing devices being designed for manufacture by 3D printing, 3D-printed ophthalmic formulations to release drugs have been one such target of investigation. In the current study, 3D-printed contact lenses designed for the controlled release of the antibiotic azithromycin were produced by vat photopolymerization, and the effect of the printer ink composition and a second curing process was investigated. The azithromycin-loaded contact lenses were composed of the cross-linking reagent polyethylene glycol diacrylate (PEGDA), PEG 400 as a solvent, a photoinitiator, and azithromycin. The 3D-printed contact lenses were fabricated successfully, and formulations with lower PEGDA concentrations produced thicker lenses. The mechanical strength of the PEGDA-based contact lenses was dependent on the amount of PEGDA and was improved by a second curing process. Drug release from 3D-printed contact lenses was reduced in the samples with a second curing process. The azithromycin-loaded contact lenses exhibited antimicrobial effects in vitro for both Gram-positive and -negative bacteria. These results suggest that 3D-printed contact lenses containing antibiotics are an effective model for treating eye infections by controlling drug release.
Assuntos
Azitromicina , Lentes de Contato , Tecnologia Farmacêutica/métodos , Preparações de Ação Retardada , Polietilenoglicóis , Liberação Controlada de Fármacos , Impressão TridimensionalRESUMO
Bioequivalence has been assessed using in vitro dissolution testing, such as in vivo predictive dissolution methodology. However, the assessment of bioequivalence should be performed carefully, considering the effect of the in vivo environment and according to the properties of the drug. The gastric emptying process is a key factor for the assessment of biopharmaceutics classification system class II (BCS class IIa) drugs with acidic properties since they cannot dissolve in the acidic stomach, but do dissolve in the small intestine (SI). The disintegration of a tablet in the stomach affects the distribution/dissolution in the SI due to the difference in the gastric emptying step, which in turn is a result of the varying formulation of the drugs. In this study, we used the reported dynamic pH change method and a novel gastric process simulation (GPS) model, which can compare the gastric emptying of particular-sized drug particles. The in vitro results were compared to clinical data using bioequivalent and bioinequivalent products of candesartan cilexetil. It was revealed that the dynamic pH change method was inappropriate, whereas the amount of filtered drug in GPS studies with 20 and 50 µm pore size filters could reflect the clinical results of all products. The evaluation of the gastric emptying process of drug particles less than 50 µm enabled us to assess the bioequivalence because they probably caused the difference in the distribution in the SI. This study demonstrated the utility of the GPS model for the assessment of bioequivalence of BCS class IIa drugs.
Assuntos
Biofarmácia , Estômago , Biofarmácia/métodos , Simulação por Computador , Solubilidade , Equivalência TerapêuticaRESUMO
Wear-resistant polymers and ceramics-based media have been used to pulverize the bulk powder of poorly water-soluble drugs to nanoscale size in conventional milling; however, contamination of such media is still an issue in the context of drug formulation manufacturing. In the present study, we developed a novel method for pulverizing the particles of a poorly water-soluble drug, ketoprofen, to nanoscale size by mixing mannitol and polypropylene glycol as a safe pulverizing medium. The ketoprofen nanoparticles were prepared using a Hoover automatic muller, equipment that traditionally has been used for the mixing of paint and ink. This process represents a novel application of this machine for the on-demand preparation of nanoparticulate formulations for use in the clinical setting. The optimal composition of the drug formulation was determined by designing an experiment consisting of the central composite design and responsive surface method. We obtained a design space that yielded ketoprofen nanoparticles with targeted particle size, poly-dispersity index, and drug release properties. We validated the manufacturing conditions by preparing ketoprofen nanoparticles in four compositions. Thus, the present study provided useful information regarding not only simple and effective contamination-free milling but also the experimental conditions need to produce nanoparticles of a poorly water-soluble drug.
Assuntos
Cetoprofeno , Nanopartículas , Manitol , Tamanho da Partícula , Composição de Medicamentos/métodos , Água , SolubilidadeRESUMO
Confectionery ingredients are expected to enhance the medication adherence of pediatric patients taking bitter-tasting drugs when adequate pediatric medicines are not available in practical settings. Gum is a familiar confectionery, and several drug-loaded gums are on the market as medicated chewing gums. In this study, medical gum tablets composed of confectionery xylitol gum and a drug (ibuprofen or acetaminophen) were prepared and evaluated for the purpose of potential hospital applications. The effect of the sintering process, a heating treatment, on the physical properties of the solid materials was also examined. The sintering process markedly improved the hardness of the gum tablets. The sintering temperature and time affected the hardness of both ibuprofen- and acetaminophen-loaded gum tablets, whereas heat treatment around the melting point of ibuprofen or xylitol and longer heat treatment resulted in failure of the preparation or a reduction in hardness. The sintered gum tablets exhibited a delayed drug release profile in artificial saliva after an in vitro chewing test. The current results provide basic and useful information about the preparation of gum-containing tablets in future clinical settings.
Assuntos
Goma de Mascar , Excipientes/química , Adesão à Medicação , Xilitol/química , Acetaminofen/química , Acetaminofen/farmacocinética , Química Farmacêutica , Criança , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Liberação Controlada de Fármacos , Humanos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Saliva/química , Comprimidos , PaladarRESUMO
3D printing technology has been applied to various fields and its medical applications are expanding. Here, we fabricated implantable 3D bio-printed hydrogel patches containing a nanomedicine as a future tailored cancer treatment. The patches were prepared using a semi-solid extrusion-type 3D bioprinter, a hydrogel-based printer ink, and UV-LED exposure. We focused on the composition of the printer ink and semi-synthesized fish gelatin methacryloyl (F-GelMA), derived from cold fish gelatin, as the main component. The low viscosity of F-GelMA due to its low melting point was remarkably improved by the addition of carboxymethyl cellulose sodium (CMC), a pharmaceutical excipient. PEGylated liposomal doxorubicin (DOX), as a model nanomedicine, was incorporated into the hydrogel and liposome stability after photo-polymerization was evaluated. The addition of CMC inhibited particle size increase. Three types of 3D-designed patches (cylinder, torus, gridlines) were produced using a 3D bioprinter. Drug release was dependent on the shape of the 3D-printed patches and UV-LED exposure time. The current study provides useful information for the preparation of 3D printed nanomedicine-based objects.
Assuntos
Bioimpressão/métodos , Doxorrubicina/análogos & derivados , Sistemas de Liberação de Medicamentos , Proteínas de Peixes/química , Gelatina/química , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacocinética , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Hidrogéis/química , Luz , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/farmacocinética , Polimerização/efeitos da radiação , Impressão Tridimensional , Adesivo Transdérmico , ViscosidadeRESUMO
The use of three-dimensional (3D) printing technology is expanding in various fields. The application of 3D printing is expected to increase in the pharmaceutical industry after 3D-printed tablets were approved by the U.S. Food and Drug Administration (FDA). Fused deposition modeling (FDM), a type of 3D printing, has been extensively studied for the manufacturing of tablets. A drug-loaded polymer filament, the ink of FDM 3D printers, can be prepared using the hot melt extrusion method or a simple drug-soaking method. In the present study, we investigate the influence of the experimental conditions on the loading of curcumin (model drug with fluorescence) into a polyvinylalcohol polymer filament using the soaking method. We show that organic solvent type (isopropanol, methanol, acetone, and ethanol), temperature (25 and 80°C), and drug concentration (2-333 mg/mL) greatly affect drug loading. Around 5% curcumin can be incorporated into the polyvinylalcohol filament using the soaking method. The drug dissolution from 3D-printed tablets depends on the drug content in the polymer filament. The incorporation of a higher amount of curcumin, which has poor water solubility, greatly delays drug dissolution. These results provide useful information on the preparation of 3D-printed tablets using a drug-loaded polymer filament obtained with the soaking method.
Assuntos
Impressão Tridimensional , Comprimidos/química , Tecnologia Farmacêutica/métodos , Curcumina/química , Liberação Controlada de Fármacos , Álcool de Polivinil/química , Solubilidade , Solventes/química , TemperaturaRESUMO
As alveolar macrophages are attractive targets for the treatment of tuberculosis, effective methods for delivery to alveolar macrophages are under development. We investigated a pulmonary formulation for the efficient delivery of high water-soluble drugs at high concentration targeting alveolar macrophages. In this study, a surfactant-coated high water-soluble drug complex (SDC, a hydrophobic dried emulsion), which can preferably target alveolar macrophages and be expected to deliver drug at a high concentration, was prepared in the first process. OCT313, a high water-soluble sugar derivative with anti-tuberculosis activity was used. Then, a unique two-solution, mixing-type nozzle was used to prepare the SDC nanoparticles in mannitol (MAN) microparticles (SDC/MAN microparticles) because it was difficult to disperse the SDC nanoparticles in aqueous solution. The single micron size of OCT313-SDC/MAN microparticles contained OCT313-SDC nanoparticles (mean particle size of OCT313-SDC nanoparticles, 277.9 nm; drug contents, 1.31 ± 0.041 wt%). We found that the treatment of SDC/MAN microparticles exhibited significantly higher drug accumulation in macrophage cells (Raw264.7 cells, 7.5-fold, at 4 h after treatment) in vitro and in alveolar macrophages in rats (9.1-fold, at 4 h after treatment) in vivo than that of drug alone. These results suggest that the SDC/MAN microparticle formulation prepared by spray drying through a two-solution mixing-type nozzle provides efficient delivery of a water-soluble drug targeting alveolar macrophages and may be useful for tuberculosis treatment.
Assuntos
Composição de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/métodos , Macrófagos Alveolares/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Administração por Inalação , Animais , Antituberculosos/farmacologia , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Pulmão/efeitos dos fármacos , Manitol , Camundongos , Nanopartículas , Células RAW 264.7 , Ratos , Ratos Wistar , TensoativosRESUMO
Pharmaceutical applications of three dimensional (3D) printing technology are increasing following the approval of 3D-printed tablets by the U.S. Food and Drug Administration. Semi-solid extrusion-type 3D printers are used to 3D print hydrogel- and paste-based materials. We previously developed tablet formulations for semi-solid extrusion-type 3D bioprinters. In the present study, we extended our study to the preparation of muco-adhesive oral film formulations to 3D bioprint mouth ulcer pharmaceuticals. We focused on hydroxypropyl methylcellulose (HPMC)-based catechin (model drug)-loaded hydrogel formulations and found that the viscosity of a hydrogel formulation is dependent on the HPMC concentration, and that viscosity is important for facile 3D printing. HPMC-based films were prepared using two different drying methods (air drying and freeze drying). The films exhibited different drug dissolution profiles, and increasing the amount of HPMC in the film delayed drug dissolution. The fabrication of HPMC-based catechin-loaded films with different shapes provides a model of individualized, on-demand pharmaceuticals. Our results support the flexible application of 3D bioprinters (semi-solid extrusion-type 3D printers) for preparing film formulations.
Assuntos
Catequina/uso terapêutico , Composição de Medicamentos/métodos , Metilcelulose/uso terapêutico , Impressão Tridimensional , Tecnologia Farmacêutica/métodos , Adesivos , Liberação Controlada de Fármacos , Derivados da Hipromelose , Metilcelulose/análogos & derivados , ViscosidadeRESUMO
Microfluidics is a promising system for efficiently optimizing the experimental conditions for preparing nanomedicines, such as self-assembled nanoparticles. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are promising drug carriers allowing sustained drug release. Here, we encapsulated the model drug curcumin, which has many pharmacological activities, into PLGA nanoparticles and investigated the effects of experimental conditions on the resulting PLGA nanoparticles using a microfluidics system with a staggered herringbone structure that can stir solutions through chaotic advection. The total flow rate and flow rate ratio of the solutions in the microfluidics system affected the diameters, polydispersity index, and encapsulation efficiency of the resulting PLGA nanoparticles and produced small, homogenous PLGA nanoparticles. The incorporation of polyethylene glycol (PEG)-PLGA into the PLGA nanoparticles reduced the particle size and improved the encapsulation efficiency. Initial burst release from the PLGA nanoparticles was prevented by the incorporation of PEG2000-PLGA. Curcumin-loaded PEGylated PLGA nanoparticles showed cytotoxicity similar to that of other formulations. This microfluidics system allows high throughput and is scalable for the efficient preparation of PLGA nanoparticles and PEGylated PLGA nanoparticles. Our results will be useful for developing novel PLGA-based polymer nanoparticles by using the microfluidics.
Assuntos
Curcumina/química , Composição de Medicamentos/instrumentação , Dispositivos Lab-On-A-Chip , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/toxicidade , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Nanopartículas/toxicidade , Poliésteres/toxicidade , Polietilenoglicóis/toxicidadeRESUMO
Gold nanoparticles (GNPs) have promising properties such as photothermal effects and could be useful for imaging and as multifunctional nanocarriers for various drugs. In this study, we synthesized polyethyleneglycol (PEG)-grafted GNPs and conjugated them with cyclodextrin (CD) to incorporate curcumin. Curcumin has anticancer effects but its therapeutic application is limited due to poor water solubility. Three types of CDs (α-, ß-, and γ-CDs) were conjugated with PEGylated GNPs and the curcumin-containing CD/PEG-conjugated GNPs (cur-CD-GNPs) were characterized. Transmission electron microscopy and dynamic light scattering results showed that these cur-CD-GNPs have a small gold nanocore (approximately 5 nm) and the average size of the three cur-CD-GNPs was approximately 25-35 nm. Curcumin was efficiently incorporated into the ß-CD solution and the loading efficiency of curcumin in ß-CD-GNPs was the highest of the three types of CD-GNPs prepared. The cytotoxic effect of cur-CD-GNPs was investigated using a human lung cancer cell line. All cur-CD-GNPs exhibited cytotoxic effects comparable to that of curcumin solution and CD-GNPs without curcumin were not cytotoxic. These results suggest that cur-CD-GNPs may be a useful multifunctional nanomedicine, although in vivo investigations are required.
Assuntos
Antineoplásicos/química , Curcumina/química , Ciclodextrinas/química , Ouro/química , Nanopartículas Metálicas/química , Polietilenoglicóis/química , Células A549 , Antineoplásicos/toxicidade , Transporte Biológico , Sobrevivência Celular/efeitos dos fármacos , Curcumina/toxicidade , Ciclodextrinas/toxicidade , Composição de Medicamentos , Ouro/toxicidade , Humanos , Nanopartículas Metálicas/toxicidade , Polietilenoglicóis/toxicidadeRESUMO
The trans platinum-chloroquine diphosphate dichloride (PtCQ) is a new type of antimalarial drug used to fight parasites resistant to traditional drugs. PtCQ is synthesized by mixing platinum and chloroquine diphosphate (CQ). This study examines two efficient methods for forming a nanodrug, PtCQ-loaded liposomes, for use as a potential antimalarial drug-delivery system: the thin drug-lipid film method to incorporate the drug into a liposomal membrane, and a remote-loading method to load the drug into the interior of a cationic liposome. The membranes accordingly comprised PEGylated neutral or cationic liposomes. PtCQ was efficiently loaded into PEGylated neutral and cationic liposomes using the thin drug-lipid film method (encapsulation efficiency, EE: 76.1±6.7% for neutral liposomes, 1 : 14 drug-to-lipid weight ratio; 70.4±9.8% for cationic liposomes, 1 : 14 drug-to-lipid weight ratio). More PtCQ was loaded into PEGylated neutral liposomes using the remote-loading method than by the thin drug-lipid film method and the EE was maximum (96.1±4.5% for neutral liposomes, 1 : 7 (w/w)). PtCQ was encapsulated in PEGylated cationic liposomes comprising various amounts of cationic lipids (0-20 mol%; EE: 96.9-92.3%) using the remote-loading method. PEGylated neutral liposomes and cationic liposomes exhibited minimum leakage of PtCQ after two months' storage at 4°C, and further exhibited little release under in vitro culture conditions at 37°C for 72 h. These results provide a useful framework for the design of future liposome-based in vivo drug delivery systems targeting the malaria parasite.
Assuntos
Antimaláricos/química , Cloroquina/análogos & derivados , Sistemas de Liberação de Medicamentos , Platina/química , Polietilenoglicóis/química , Cloroquina/química , Liberação Controlada de Fármacos , Resistência a Medicamentos , Lipídeos/química , Lipossomos , Malária , Plasmodium falciparumRESUMO
Three-dimensional (3D) printers have been applied in many fields, including engineering and the medical sciences. In the pharmaceutical field, approval of the first 3D-printed tablet by the U.S. Food and Drug Administration in 2015 has attracted interest in the manufacture of tablets and drugs by 3D printing techniques as a means of delivering tailor-made drugs in the future. In current study, polyvinylalcohol (PVA)-based tablets were prepared using a fused-deposition-modeling-type 3D printer and the effect of 3D printing conditions on tablet production was investigated. Curcumin, a model drug/fluorescent marker, was loaded into PVA-filament. We found that several printing parameters, such as the rate of extruding PVA (flow rate), can affect the formability of the resulting PVA-tablets. The 3D-printing temperature is controlled by heating the print nozzle and was shown to affect the color of the tablets and their curcumin content. PVA-based infilled tablets with different densities were prepared by changing the fill density as a printing parameter. Tablets with lower fill density floated in an aqueous solution and their curcumin content tended to dissolve faster. These findings will be useful in developing drug-loaded PVA-based 3D objects and other polymer-based articles prepared using fused-deposition-modeling-type 3D printers.
Assuntos
Excipientes , Álcool de Polivinil , Impressão Tridimensional , Comprimidos , Curcumina/administração & dosagem , Polímeros , Tecnologia Farmacêutica/métodosRESUMO
Ranibizumab is a humanized monoclonal antibody fragment against vascular endothelial growth factor (VEGF)-A and is widely used to treat age-related macular degeneration (AMD) caused by angiogenesis. Ranibizumab has a short half-life in the eye due to its low molecular weight and susceptibility to proteolysis. Monthly intravitreal injection of a large amount of ranibizumab formulation is a burden for both patients and medical staff. We therefore sought to develop a sustainable release system for treating the eye with ranibizumab using a drug carrier. A ranibizumab biosimilar (RB) was incorporated into microparticles of poly(lactic-co-glycolic acid) (PLGA) biodegradable polymer. Ranibizumab was sustainably released from PLGA microparticles (80+% after 3 weeks). Assay of tube formation by endothelial cells indicated that RB released from PLGA microparticles inhibited VEGF-induced tube formation and this tendency was confirmed by a cell proliferation assay. These results indicate that RB-loaded PLGA microparticles are useful for sustainable RB release and suggest the utility of intraocular sustainable release systems for delivering RB site-specifically to AMD patients.
Assuntos
Medicamentos Biossimilares/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Láctico/metabolismo , Microesferas , Ácido Poliglicólico/metabolismo , Ranibizumab/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Medicamentos Biossimilares/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ácido Láctico/administração & dosagem , Ácido Poliglicólico/administração & dosagem , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ranibizumab/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/administração & dosagemRESUMO
In the development of a drug for intra-articular administration, a sustained-release formulation is desirable since it is difficult to sustain the effects of conventional injections due to fast drug leakage from the joint cavity. In this study, we prepared sustained release gel formulations for intra-articular administration containing indocyanine green (ICG) as a model drug to follow its fate after intra-articular administration in rats with in-vivo imaging system (IVIS). ICG administered as an aqueous solution leaked from the joint cavity in a short time and was excreted out of the body within a day. On the other hand, ICG in the sustained-release formulations was retained and released in the joint cavity for a week. Next, we prepared a sustained-release formulation with hyaluronic acid (HA) as the gel base containing a pain-relief drug (Drug A). We had administered it and other formulations into the rat knee where we injected bradykinin to evaluate their walking distance after 1 and 3 d. The effect of an aqueous solution of Drug A disappeared on day 3. The HA gel formulation without Drug A was more effective than the aqueous solution. The HA gel formulation with Drug A was the most effective; the walking distance was about 85% of the baseline on day 3. This study showed that the gel formulations were effective to sustain the release of a drug in the knee joint, and that the combination of a pain-relief drug with HA gel was effective to improve the mobility of the acute pain model rats.
Assuntos
Analgésicos/administração & dosagem , Ácido Hialurônico/administração & dosagem , Articulação do Joelho/metabolismo , Dor/tratamento farmacológico , Analgésicos/farmacologia , Animais , Bradicinina , Corantes/administração & dosagem , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Géis , Ácido Hialurônico/farmacologia , Verde de Indocianina/administração & dosagem , Injeções Intra-Articulares , Masculino , Dor/induzido quimicamente , Ratos Sprague-Dawley , CaminhadaRESUMO
CONTEXT: The development of taste-masking technologies for foods and drugs is essential because it would enable people to consume and receive healthy and therapeutic effect without distress. OBJECTIVE: In the current study, in order to develop a novel method to prepare nanocomposite particles (microparticles containing bitter nanoparticles) in only one step, by using spray drying, a two-solution mixing nozzle-equipped spray dryer that we previously reported was used. The nanocomposite particles with or without poorly water-soluble polymers prepared using our spray-drying technique were characterized. METHODS: (1) The organic solution containing quinine, a model of bitter compound and poorly water-soluble polymers and (2) sugar alcohol (mannitol) aqueous solution were separately flown in tubes and two solutions were spray dried through two-solution type spray nozzle to prepare polymer-blended quinine nanocomposite particles. Mean diameters of nanoparticles, taste-masking effect and dissolution rate of quinine were evaluated. RESULTS: The results of taste masking by taste sensor suggested that the polymer (Eudragit EPO, Eudragit S100 or Ethyl cellulose)-blended quinine nanocomposite particles exhibited marked masking of instrumental quinine bitterness compared with the quinine nanocomposite particles alone. Quinine nanocomposite formulations altered the quinine dissolution rate, indicating that they can control intestinal absorption of quinine. CONCLUSION: These results suggest that polymer-blended quinine composite particles prepared using our spray-drying technique are useful for masking bitter tastes in the field of food and pharmaceutical industry.
Assuntos
Nanocompostos/química , Polímeros/química , Quinina/química , Percepção Gustatória/efeitos dos fármacos , Paladar/efeitos dos fármacos , Química Farmacêutica/métodos , Dessecação/métodos , Manitol/química , Nanopartículas/química , Tamanho da Partícula , Solubilidade , Soluções/química , Tecnologia Farmacêutica/métodos , Água/químicaRESUMO
Malaria is one of the most prevalent parasitic diseases and is most widespread in tropical regions. The malarial parasite grows and reproduces in erythrocytes during its life cycle, resulting in programmed erythrocyte death, termed eryptosis. Lipid scrambling, which occurs following the exposure of anionic lipids such as phosphatidylserine (PS) on the outer surface of erythrocytes, is a characteristic physical change that occurs early during eryptosis. Here, we prepared "PS specific peptide (PSP)"-conjugated liposomes (PSP-liposomes) and investigated whether PSP-liposomes hold promise as a novel strategy for actively targeting eryptosis. Eryptosis was induced by exposing red blood cells (RBCs) to ionomycin, a known calcium ionophore. When PSP liposomes were mixed with either RBCs or RBCs undergoing eryptosis (E-RBCs), the amount of PSP-liposome bound to E-RBCs was much higher than the amount bound to RBCs. However, the amount of PSP-liposome bound to E-RBCs was significantly inhibited by the presence of annexin V protein, which binds specifically to PS. These results suggest that PSP-liposomes could be an effective drug nanocarrier for treating E-RBCs and malaria-infected erythrocytes.
Assuntos
Apoptose/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Lipídeos/farmacologia , Lipossomos/farmacologia , Peptídeos/farmacologia , Animais , Modelos Animais de Doenças , Eritrócitos/parasitologia , Lipídeos/química , Lipossomos/química , Malária , Masculino , Camundongos , Peptídeos/química , PlasmodiumRESUMO
CONTEXT: X-ray inspection equipment is widely used to detect missing materials and defective goods in opaque containers. Its application has been expanded to the pharmaceutical industry to detect the presence of drug tablets in aluminum foil press-through packaging. However, the effect of X-rays on the pharmaceutical quality of drug tablets is not well known. OBJECTIVE: In this study, the effect of X-rays on the pharmaceutical quality of drug tablets was investigated. METHODS: Exposure of acetaminophen, loxoprofen and mefenamic acid tablets to X-ray doses of 0.34 mGy (thrice the dose by X-ray scanning) to 300 Gy (maximum dose from our X-ray equipment) was demonstrated, and the samples were evaluated by formulation tests. RESULTS: Exposure to X-rays did not affect the pharmaceutical quality of the drug content. The samples exposed to X-rays exhibited almost the same profile in formulation tests (dissolution test, disintegrating test and hardness test) as control samples (0 Gy). The combination of X-ray exposure with accelerated temperature and humidity tests (six months) also did not affect the pharmaceutical quality. The color change of light-sensitive drugs (nifedipine and furosemide tablets) after X-ray exposure was negligible (< 1.0). In contrast, tablet color was remarkably changed by light from a D65 lamp. CONCLUSION: The X-ray scanning and X-ray exposure under our experimental conditions did not affect the pharmaceutical quality of drug tablets.
Assuntos
Indústria Farmacêutica/métodos , Embalagem de Medicamentos , Preparações Farmacêuticas/química , Raios X , Cor , Estabilidade de Medicamentos , Dureza , Umidade , Controle de Qualidade , Solubilidade , Comprimidos , TemperaturaRESUMO
Intranasal administration has attracted increasing attention as a drug delivery approach based on nose-to-brain drug delivery from the nasal cavity to brain tissue directly, bypassing the blood-brain barrier. However, application of the method to poorly water-soluble drugs is potentially limited due to low aqueous solubility and dissolution, which can hinder drug transfer to brain tissue. In the present study, we focused on an amorphous solid dispersion (ASD) technique to improve drug dissolution. A carbamazepine-loaded ASD model drug was prepared using the solvent evaporation method (ASD-1). After screening six water-soluble polymer carriers, polyvinyl alcohol (PVA)-based ASD-1 formulation exhibited the most rapid and highest drug dissolution under experimental conditions in the nasal cavity (pH 6.0). A carbamazepine suspension dispersed with a PVA-ASD-1 formulation exhibited enhanced drug delivery into plasma and brain tissue of rats in vivo. A spray-dried powder formulation of PVA-ASD (PVA-ASD-2) exhibited improved drug dissolution and in vivo drug transfer. Our key finding is that the spray-dried PVA-ASD-2 formulation exhibited higher brain/plasma ratios than the PVA-ASD-1 suspension formulation. Our physical characterization data and demonstration of improved drug transfer suggest that ASD-based intranasal formulations hold promise for drug delivery to the brain.