RESUMEN
Currently, despite many active compounds have been introduced to the treatment, cancer remains one of the most vital causes of mortality and reduced quality of life. Conventional cancer treatments may have undesirable consequences due to the continuous differentiating, dynamic and heterogeneous nature of cancer. Recent advances in the field of cancer treatment have promoted the development of several novel nanoformulations. Among them, the lipid coated nanosized drug delivery systems have gained an increasing attention by the researchers in this field owing to the attractive properties such as high stability and biocompatibility, prolonged circulation time, high drug loading capacity and superior in vivo efficacy. They possess the advantages of both the liposomes and polymeric nanoparticles which makes them a chosen one in the field of drug delivery and targeting. Core-shell type lipid-coated nanoparticle systems, which provide the most prominent advantages of both liposomes such as biocompatibility and polymeric/inorganic nanoparticles such as mechanic properties, offer a new approach to cancer treatment. This review discusses design and production procedures used to prepare lipid-coated nanoparticle drug delivery systems, their advantages and multifunctional role in cancer therapy and diagnosis, as well as the applications they have been used in.
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Nanopartículas/química , Neoplasias , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Lípidos/química , Neoplasias/tratamiento farmacológico , Calidad de VidaRESUMEN
Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine - the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment - was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid-polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the hepatic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.
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Inhibidores Enzimáticos/farmacología , Hexoquinasa/antagonistas & inhibidores , Indazoles/farmacología , Lípidos/química , Nanopartículas , Polímeros/química , Próstata/efectos de los fármacos , Hiperplasia Prostática/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Modelos Animales de Enfermedad , Composición de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/toxicidad , Hexoquinasa/metabolismo , Indazoles/química , Indazoles/toxicidad , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Nanomedicina , Próstata/enzimología , Próstata/patología , Hiperplasia Prostática/enzimología , Hiperplasia Prostática/patología , RatasRESUMEN
Drug resistance is one of the main problems of cancer treatment. For this reason, combination therapy is commonly used for years. The combination of a chemotherapeutic, carboplatin, and the epigenetic drug decitabine is a new approach to modulate drug resistance. Nanoparticulate systems can overcome the drawbacks associated with the drug combinations. An analytical method that can detect and quantify carboplatin and decitabine which is encapsulated into the nanoparticles is necessary for nanoparticle development. In the literature, there is no analytical method in which carboplatin and decitabine are determined simultaneously. The primary purpose of this study is to develop and validate a novel, and stability-indicating high-performance liquid chromatography method for simultaneous determination of carboplatin and decitabine in pharmaceutical preparations in addition to developing the first nanoformulation for this drug combination. Therefore, various experimental parameters were optimized. The chromatographic separation was achieved using an XSelect® CSH C18 (250 × 4.6 mm I.D., 5 µm) column and a mobile phase consisting of methanol:water (containing 0.1% phosphoric acid) (3:97, v/v). The mobile phase pH was adjusted to 7.0 with 5 M NaOH. The developed method was successfully applied for the simultaneous determination and quantification of carboplatin and decitabine co-encapsulated in nanoparticles and released into in vitro dissolution medium.
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Carboplatino/análisis , Decitabina/análisis , Nanopartículas/química , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Estabilidad de MedicamentosRESUMEN
Healing fractures resulting from bone disorders such as osteoporosis, osteoarthritis, osteomyelitis, and osteosarcoma remain a significant clinical challenge. In this chapter, we focus on scaffold based local drug delivery applications for promoting bone regeneration. For this purpose, we first review bone disorders, which require drug treatment and current fabrication techniques for bone tissue scaffold as a drug carrier. Next, we address the role of antimicrobial agents, anti-inflammatory drugs, anti-cancer drugs and bisphosphonates in promoting vascularized bone regeneration and discuss various local therapeutic delivery strategies for controlled and sustained drug delivery. Specifically, this review addresses the concept of drug loaded scaffold design and local drug release effects on bone regeneration. We conclude this review with a discussion of local drug delivery approaches to bone regeneration and discuss why it has the potential to be more efficient than traditional bone treatment methods.
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Regeneración Ósea , Sistemas de Liberación de Medicamentos , Andamios del Tejido , Enfermedades Óseas/terapia , HumanosRESUMEN
Recent clinical and epidemiological researches have declared that non-steroidal anti-inflammatory agents may display as antineoplastic agents and indicate pro-apoptotic and antiproliferative effects on cancer cells. The major purpose of this research was to develop a novel poly(ethyleneglycol)-block-poly(ε-caprolactone) (PEG-b-PCL) nano-sized particles encapsulated with nimesulide (NMS), a selective COX-2 inhibitor, and to evaluate its anticancer activity against MCF-7 breast cancer cells. NMS-encapsulated PEG-b-PCL nanoparticles were fabricated using three different production techniques: (i) by emulsion-solvent evaporation using a high shear homogenizer, (ii) by emulsion-solvent evaporation using an ultrasonicator, and (iii) by nanoprecipitation. Nanoparticles were evaluated with respect to the entrapment efficiency, size characteristics, drug release rates, thermal behavior, cell viability assays, and apoptosis. The resulting nanoparticles were found to be spherical shapes with negative surface charges. The average diameter of all nanoparticles ranged between 148.5 and 307.2 nm. In vitro release profiles showed that all nanoparticles exhibited a biphasic release pattern. NMS-loaded PEG-b-PCL nanoparticles demonstrated significant anticancer activity against MCF-7 breast cancer cells in a dose-dependent manner, and the effects of nanoparticles on cell proliferation were significantly affected by the preparation techniques. The nanoparticles developed in this work displayed higher potential for the NMS delivery against breast cancer treatment for the future.
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Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Nanopartículas/química , Sulfonamidas/química , Sulfonamidas/farmacología , Antiinflamatorios no Esteroideos/síntesis química , Antiinflamatorios no Esteroideos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Emulsiones/química , Emulsiones/farmacología , Femenino , Humanos , Lactonas/química , Células MCF-7 , Tamaño de la Partícula , Polietilenglicoles/química , Solventes/químicaRESUMEN
Fulvestrant is used for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Several reversed-phase columns with variable silica materials, diameters, lengths, etc., were tested for the optimization study. A good chromatographic separation was achieved using a Waters X-Terra RP(18) column (250 × 4.6 mm i.d. × 5 µm) and a mobile phase, consisting of a mixture of acetonitrile-water (65:35; v/v) containing phosphoric acid (0.1%). The separation was carried out 40 °C with detection at 215 nm.The calibration curves were linear over the concentration range between 1.0-300 and 1.0-200 µg/mL for standard solutions and biological media, respectively. The proposed method is accurate and reproducible. Forced degradation studies were also realized. This fully validated method allows the direct determination of fulvestrant in dosage form and biological samples. The average recovery of the added fulvestrant amount in the samples was between 98.22 and 104.03%. The proposed method was also applied for the determination of fulvestrant from the polymeric-based nanoparticle systems. No interference from using polymers and other excipients was observed in in vitro drug release studies. Therefore an incorporation efficiency of fulvestrant-loaded nanoparticle could be determined accurately and specifically.
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Cromatografía de Fase Inversa/métodos , Estradiol/análogos & derivados , Nanopartículas/química , Estradiol/análisis , Estradiol/química , Estradiol/farmacocinética , Fulvestrant , Humanos , Cinética , Ácido Láctico , Límite de Detección , Modelos Lineales , Polietilenglicoles , Poliglactina 910 , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Reproducibilidad de los ResultadosRESUMEN
This investigation aimed to develop nimesulide (NMS)-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticulate formulations as a biodegradable polymeric drug carrier to treat rheumatoid arthritis. Polymeric nanoparticles (NPs) were prepared with two different nonionic surfactants, vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and poly(vinyl alcohol) (PVA), using an ultrasonication solvent evaporation technique. Nine batches were formulated for each surfactant using a 3(2) factorial design for optimal concentration of the emulsifying agents, 0.03-0.09% for vitamin E TPGS and 2-4% for PVA. The surfactant percentage and the drug/polymer ratio (1:10, 1:15, 1:20) of the NMS-loaded NPs were investigated based on four responses: encapsulation efficiency, particle size, the polydispersity index, and the surface charge. The response surface plots and linearity curves indicated a relationship between the experiment's responses and a set of independent variables. The NPs produced with both surfactants exhibited a negative surface charge, and scanning electron micrographs revealed that all of the NPs were spherical in shape. A narrower size distribution and higher drug loadings were achieved in PVA-emulsified PLGA NPs than in the vitamin E TPGS emulsified. Decreasing amounts of both nonionic surfactants resulted in a reduction in the emulsion's viscosity, which led to a decrease in the particle size of NPs. According to the ANOVA results obtained in this present research, vitamin E TPGS exhibited the best correlation between the independent variables, namely drug/polymer ratio and the surfactant percentage, and the dependent variables (encapsulation efficiency R(2) = 0.9603, particle size R(2) = 0.9965, size distribution R(2) = 0.9899, and surface charge R(2) = 0.8969) compared with PVA.
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Emulsiones/química , Ácido Láctico/química , Nanopartículas/química , Ácido Poliglicólico/química , Sulfonamidas/química , Tensoactivos/química , Química Farmacéutica/métodos , Portadores de Fármacos/química , Tamaño de la Partícula , Polietilenglicoles/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros/química , Alcohol Polivinílico/química , Vitamina E/análogos & derivados , Vitamina E/químicaRESUMEN
CONTEXT: The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells. OBJECTIVE: In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined. METHODS: NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays. RESULTS: NPs had a spherical shape and a negative zeta potential, and their size ranged between 170-231 nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs. CONCLUSION: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.
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Adenocarcinoma/tratamiento farmacológico , Antineoplásicos/farmacología , Neoplasias del Colon/tratamiento farmacológico , Inhibidores de la Ciclooxigenasa 2/farmacología , Portadores de Fármacos/farmacología , Nanopartículas/química , Tiazinas/farmacología , Tiazoles/farmacología , Adenocarcinoma/metabolismo , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Antineoplásicos/metabolismo , Transporte Biológico , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica , Neoplasias del Colon/metabolismo , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Inhibidores de la Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa 2/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Portadores de Fármacos/metabolismo , Estabilidad de Medicamentos , Células HT29 , Humanos , Cinética , Ácido Láctico/química , Meloxicam , Peso Molecular , Tamaño de la Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Alcohol Polivinílico/análisis , Solubilidad , Propiedades de Superficie , Tiazinas/administración & dosificación , Tiazinas/química , Tiazinas/metabolismo , Tiazoles/administración & dosificación , Tiazoles/química , Tiazoles/metabolismoRESUMEN
Floating dosage forms of acetylsalicylic acid, used for its antithrombotic effect, were developed to prolong gastric residence time and increase bioavailability. In the two-layer tablet formulation, hydroxypropyl methylcellulose (HPMC) of high viscosity and an effervescent mixture of citric acid and sodium bicarbonate formed the floating layer. The release layer contained the drug, direct tableting agent and different types of matrix-forming polymers such as HPMC of low viscosity, sodium carboxymethylcellulose and chitosan. Tablets were prepared using a direct compression technique. The effect of formulation variables on physicochemical and floating properties and the drug release from tablets were investigated. Floating ability was dependent on the amount of effervescent agent and gel-forming polymer of the floating layer. Drug release was prolonged to 8 hours by changing the type and viscosity of the matrix-forming polymer in the drug-loading layer and all formulations showed a diffusion release mechanisms.
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Aspirina/química , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos , Excipientes/química , Fibrinolíticos/química , Mucosa Gástrica/metabolismo , Aspirina/metabolismo , Disponibilidad Biológica , Quitosano/química , Ácido Cítrico/química , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/metabolismo , Fibrinolíticos/metabolismo , Humanos , Derivados de la Hipromelosa , Metilcelulosa/análogos & derivados , Metilcelulosa/química , Modelos Teóricos , Polímeros/química , Presión , Bicarbonato de Sodio/química , Solubilidad , Estómago/química , Comprimidos/química , Factores de Tiempo , ViscosidadRESUMEN
In this study, ethylcellulose (EC)-based microsphere formulations were prepared without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen as a hydrophilic model drug and used at different drug/polymer ratios in the microspheres. The aim of the work was to evaluate the influence of plasticizer ratio on the drug release rate and physicochemical characteristics of EC-based matrix-type microspheres. The resulting microspheres were evaluated for encapsulation efficiency, particle size and size distribution, surface morphology, total pore volume, thermal characteristics, drug release rates, and release mechanism. Results indicated that the physicochemical properties of microspheres were strongly affected by the drug/polymer ratio investigated and the concentration of TEC used in the production technique. The surface morphology and pore volume of microspheres significantly varied based on the plasticizer content in the formulation. DH release rate from EC-based matrix-type microspheres can be controlled by varying the DH to polymer and plasticizer ratios. Glass transition temperature values tended to decrease in conjunction with increasing amounts of TEC. Consequently, the various characteristics of the EC microspheres could be modified based on the plasticized ratio of TEC.
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Citratos/química , Diltiazem/química , Portadores de Fármacos , Glicoles de Etileno/química , Plastificantes/química , Química Farmacéutica , Composición de Medicamentos , Cinética , Microesferas , Tamaño de la Partícula , Porosidad , Solubilidad , Propiedades de Superficie , Tecnología Farmacéutica/métodos , Temperatura de TransiciónRESUMEN
The objective of this research was to develop microsphere-based once-daily modified release tablet formulations of diltiazem hydrochloride (DH), a potent calcium channel blocker used in angina pectoris. For this purpose, DH-loaded microspheres were prepared by the solvent evaporation technique using Eudragit RS 100. The effect of variation in the drug/polymer ratio on the physical and release characteristics of the microspheres was investigated. After the selection of the suitable microspheres, tablets were compressed using Compritol 888 ATO, Ludipress and Cellactose 80 as different direct tableting agents and excipients. As a result, modified release tablet formulations of DH-loaded microspheres were designed successfully for oral administration once rather than two or three times a day in angina pectoris.
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Angina de Pecho/tratamiento farmacológico , Preparaciones de Acción Retardada/química , Diltiazem/administración & dosificación , Comprimidos/química , Resinas Acrílicas , Administración Oral , Bloqueadores de los Canales de Calcio , Excipientes , Ácidos Grasos , Humanos , MicroesferasRESUMEN
In this study, development of modified release tablet formulations containing diltiazem hydrochloride-loaded microspheres to be taken once rather than two or three times a day was attempted. For this purpose, ethylcellulose microspheres were prepared by emulsion-solvent evaporation technique. The influence of emulsifier type and drug/polymer ratio on production yield, encapsulation efficiency, particle size, surface morphology and in-vitro release characteristics of the microspheres was evaluated. Suitable microspheres were selected and tabletted using different tabletting agents, Ludipress, Cellactose80, Flow-Lac100 and excipients Compritol888 ATO, KollidonSR. Tablets were evaluated from the perspective of physical and in-vitro drug release characteristics. It was seen that type and ratio of the excipients played an important role in the tabletting of the microspheres. As a result, two tablet formulations containing 180 mg diltiazem hydrochloride and using either Compritol888 ATO or KollidonSR were designed successfully and maintained drug release for 24 h with zero order and Higuchi kinetics, respectively.
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Bloqueadores de los Canales de Calcio/farmacocinética , Celulosa/análogos & derivados , Diltiazem/farmacocinética , Soluciones Esclerosantes/farmacocinética , Tampones (Química) , Bloqueadores de los Canales de Calcio/química , Celulosa/química , Celulosa/farmacocinética , Celulosa/ultraestructura , Preparaciones de Acción Retardada , Diltiazem/química , Composición de Medicamentos/métodos , Estudios de Evaluación como Asunto , Excipientes , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Microesferas , Tamaño de la Partícula , Soluciones Esclerosantes/química , Solubilidad , Comprimidos , Agua/químicaRESUMEN
Increased small bowel nitric oxide synthase (NOS) activity has been suspected as a cause of postnatal intestinal dysmotility in gastroschisis. The effect of continuous delivery of methylene blue loaded polymer (MBLP) hydroxy-propyl methyl cellulose-ethyl cellulose (HPEC-MC) and daily injection of methylene blue (MB) on the intestinal damage (ID) was evaluated using a chick embryo gastroschisis model. Fourteen-day-old fertilized chick eggs were divided into five groups. In the control (C) group, no intervention was performed. In the sham (S) group, the allantoic and amniotic membranes were opened to create a common cavity that resembles the amniotic cavity in human. In the gastroschisis only (GO) group, a defect in the abdominal wall of the embryo was made, and intestinal loops were exteriorized following connection of amniotic and allantoic cavities. In the gastroschisis plus methylene blue (G+MB) group, gastroschisis was created and MB administered into the amnioallantoic cavity (AAC) by daily injections for 5 days. In the gastroschisis plus methylene blue loaded polymer (G+MBLP) group, MBLP was placed into AAC after gastroschisis was created. At the end of the 19th day of incubation, intestinal morphological changes were investigated macroscopically and microscopically. Although the survival rates were decreased in the chick embryos with creation of gastroschisis compared with C and S groups ( p<0.001), the survival rates were increased in G+MBLP group (76.92%) when compared with the GO group (41%) ( p<0.001). Because of multiple intervention of embryos, higher mortality was observed in the G-MB group (75.61%). Macroscopic and microscopic scores of ID and mean intestinal wall thickness were significantly higher in the GO group when compared with C, S, G+MB, and G+MBLP groups ( p<0.001). The mean score of intestinal ganglia morphology was significantly increased and the total number of ganglion cells was significantly decreased in the GO group when compared with C, S, G+MB, and G+MBLP groups ( p<0.001). It is possible to decrease intrauterine intestinal morphological changes in gastroschisis by inhibiting NOS. As a first preliminary study, we believe that use of MBLP may be an alternative for fetal treatment by eliminating the harmful effects of multiple interventions or amniotic fluid exchanges.
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Inhibidores Enzimáticos/administración & dosificación , Motilidad Gastrointestinal/efectos de los fármacos , Gastrosquisis/complicaciones , Enfermedades Intestinales/tratamiento farmacológico , Intestinos/efectos de los fármacos , Azul de Metileno/administración & dosificación , Administración Tópica , Líquido Amniótico/efectos de los fármacos , Animales , Embrión de Pollo , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Ganglios Autónomos/patología , Motilidad Gastrointestinal/fisiología , Enfermedades Intestinales/etiología , Enfermedades Intestinales/fisiopatología , Intestinos/patología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Óxido Nítrico Sintasa/fisiologíaRESUMEN
In this study, suitable microsphere formulations were designed in order to provide the absorption of a high polar drug through nasal mucosa. For this purpose, gentamicin sulfate (GS) was chosen as a model drug and used at different drug/polymer ratios in the microsphere formulations. The microspheres were prepared by spray drying technique. Hydroxypropyl methylcellulose was used as a mucoadhesive polymer in the formulations to increase the residence time of the microspheres on the mucosa. Sodium cholate was added into the formulations for increasing the absorption of GS through nasal mucosa. The in vitro characteristics of the microspheres were determined. The microspheres were evaluated with respect to the particle size, production yield, encapsulation efficiency, shape and surface properties, drug-polymer interaction, mucoadhesive property, in vitro drug release and suitability for nasal drug delivery.