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In this study, two licensed total parenteral nanoemulsion formulations (Clinoleic® and Intralipid®) were loaded with ciprofloxacin (CP). The physicochemical characteristics and stability profiles of the formulations were investigated using a range of drug concentrations. Furthermore, formulation stability was evaluated over a period of six months at room temperature (RT) or 4 °C. Loading CP into nanoemulsions resulted in no significant differences in their measured droplet size, polydispersity index (PI), zeta potential, and pH. Drug entrapment efficiency (EE) was relatively high for all formulations, regardless of nanoemulsion type, and the drug release was sustained over 24 h. Stability studies of all formulations were performed at 4 °C and RT for 180 and 60 days, respectively. At 4 °C for 180 days, both Clinoleic® and Intralipid® formulations at a range of drug concentrations (1-10 mg/ml) showed high stabilities measured periodically by the average droplet sizes, PI, pH, and zeta potential values. Similar results, but pH values, were shown when the formulations for both nanoemulsion stored at RT for 60 days. Overall, this study has shown that CP was successfully loaded into clinically licensed TPN lipid nanoemulsions. The resultant CP-loaded nanoemulsion formulations demonstrated desirable physicochemical properties and were stable upon storage at 4 °C for up to six months.
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Antibacterianos/administración & dosificación , Ciprofloxacina/administración & dosificación , Portadores de Fármacos/química , Emulsiones Grasas Intravenosas/química , Nanoestructuras/química , Fosfolípidos/química , Aceites de Plantas/química , Aceite de Soja/química , Disponibilidad Biológica , Composición de Medicamentos , Liberación de Fármacos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Emulsiones/química , Concentración de Iones de Hidrógeno , Tamaño de la PartículaRESUMEN
Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma.
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Paclitaxel/química , Plasma/química , Albúminas/química , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Química Farmacéutica/métodos , Portadores de Fármacos/química , Glicerol/análogos & derivados , Glicerol/química , Infusiones Intravenosas/métodos , Rayos Láser , Neoplasias/tratamiento farmacológico , Nefelometría y Turbidimetría/métodos , Ratas , Ratas WistarRESUMEN
Proliposome formulations containing salbutamol sulphate (SS) were developed using spray drying, and the effects of carrier type (lactose monohydrate (LMH) or mannitol) and lipid to carrier ratio were evaluated. The lipid phase comprised soy phosphatidylcholine (SPC) and cholesterol (1:1), and the ratios of lipid to carrier were 1:2, 1:4, 1:6, 1:8 or 1:10 w/w. X-ray powder diffraction (XRPD) revealed an interaction between the components of the proliposome particles, and scanning electron microscopy (SEM) showed that mannitol-based proliposomes were uniformly sized and spherical, whilst LMH-based proliposomes were irregular and relatively large. Using a two-stage impinger (TSI), fine particle fraction (FPF) values of the proliposomes were higher for mannitol-based formulations, reaching 52.6%, which was attributed to the better flow properties when mannitol was used as carrier. Following hydration of proliposomes, transmission electron microscopy (TEM) demonstrated that vesicles generated from mannitol-based formulations were oligolamellar, whilst LMH-based proliposomes generated 'worm-like' structures and vesicle clusters. Vesicle size decreased upon increasing carrier to lipid ratio, and the zeta potential values were negative. Drug entrapment efficiency (EE) was higher for liposomes generated from LMH-based proliposomes, reaching 37.76% when 1:2 lipid to carrier ratio was used. The in vitro drug release profile was similar for both carriers when 1:6 lipid to carrier ratio was used. This study showed that spray drying can produce inhalable proliposome microparticles that can generate liposomes upon contact with an aqueous phase, and the FPF of proliposomes and the EE offered by liposomes were formulation-dependent.
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Aerosoles , Nebulizadores y Vaporizadores , Lactosa/química , Liposomas/química , Manitol/química , Tamaño de la PartículaRESUMEN
Formulation of protein and peptide drugs with sustained release properties is crucial to enhance their therapeutic effect and minimize administration frequency. In this study, immunomodulating polymeric systems were designed by manufacturing PHBHHx nanoparticles (NPs) containing thymopentin (TP5). The release profile of the drug was studied over a period of 7 days. The PHBHHx NPs containing TP5-phospholipid (PLC) complex (TP5-PLC) displayed a spherical shape with a mean size, zeta potential, and encapsulation efficiency of 238.9 nm, -32.0 mV, and 72.81%, respectively. The cytotoxicity results showed the PHBHHx NPs had a relatively low toxicity in vitro. TP5 entrapped in the NPs could hardly release in vitro, while the NPs had longer than 7 days release duration after a single subcutaneous injection in Wistar rats. The immunodepression rat model was built to evaluate the immunomodulating effects of TP5-PLC-NPs in vivo. The results of T-lymphocyte subsets (CD3(+), CD4(+), CD8(+), and CD4(+)/CD8(+) ratio) analysis and superoxide dismutase (SOD) values suggested that TP5-PLC-NPs had stronger immunoregulation effects than TP5 solution. In conclusion, an applicable approach to markedly enhancing the loading of a water-soluble peptide into a hydrophobic polymer matrix has been introduced. Thus, TP5-PLC-NPs are promising nanomedicine systems for sustained release effects of TP5.
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Glycine max/química , Nanopartículas/química , Fosfolípidos/química , Polímeros/química , Timopentina/química , Timopentina/inmunología , Adyuvantes Inmunológicos/química , Animales , Masculino , Ratas , Ratas WistarRESUMEN
Paclitaxel was loaded into licensed parenteral nutrition nanoemulsions (Clinoleic® and Intralipid®) using bath sonication, and the stability of the formulations was investigated following storage for two weeks at room temperature or at 4 °C. In general, Clinoleic droplets were smaller than Intralipid droplets, being around 255 and 285 nm, respectively, for blank and freshly loaded emulsions. Regardless of storage temperature, the Clinoleic exhibited a very slight or no increase in droplet size upon storage, whilst the droplet size of the Intralipid emulsion increased significantly. The droplet size of both emulsions was minimally affected by paclitaxel concentration within the range of 0, 1, 3 and 6 mg/ml. The pH of both emulsions markedly decreased upon storage at room temperature, which was possibly attributed to the production of fatty acids resulting from phospholipid hydrolysis. However, at 4 °C, the pH of Clinoleic emulsion was unaffected by storage or paclitaxel concentration while the Intralipid emulsion demonstrated a trend for pH reduction. Both nanoemulsions had a negative zeta potential, with the Clinoleic formulations having the highest charge, possibly explaining the better size stability of this emulsion. Overall, this study has shown that paclitaxel was successfully loaded into clinically licensed parenteral emulsions and that Clinoleic showed greater stability than the Intralipid.
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Antineoplásicos Fitogénicos/administración & dosificación , Emulsiones Grasas Intravenosas/química , Paclitaxel/administración & dosificación , Fosfolípidos/química , Aceites de Plantas/química , Aceite de Soja/química , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Emulsiones/química , TemperaturaRESUMEN
Fenpropathrin (FNP) is a man-made insecticide of to the pyrethroid class, commonly employed in agricultural and horticultural practices. However, it has a prolonged persistence in the environment. Sambucus nigra, also referred to as SN, is a botanical species recognized for its notable antioxidant characteristics. The objective of this study was to examine if SN extract could mitigate the reproductive toxicity induced by FNP in rats. A total of thirty rats were categorized into six distinct groups: a control group with no treatment, two groups getting SN extract at varying doses, a group receiving FNP, and two groups receiving both FNP and SN extract. The exposure to FNP led to a decline in the number and movement of sperm, lowered levels of testosterone, and reduced the activity of the StAR gene in the FNP group compared to the control group (p < 0.05). In addition, FNP resulted in a significant increase in malondialdehyde levels with a significant drop in GSH content compared to the control group (p < 0.05). Also, a significant increase in the expression of caspase 3. Nevertheless, the administration of SN extract alleviated these effects and reinstated spermatogenesis, thereby bringing the parameters closer to those observed in the control group. The data indicate that FNP can induce testicular harm and infertility, but SN extract can mitigate these detrimental consequences.
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Apoptosis , Estrés Oxidativo , Extractos Vegetales , Piretrinas , Sambucus nigra , Animales , Masculino , Piretrinas/toxicidad , Extractos Vegetales/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Apoptosis/efectos de los fármacos , Sambucus nigra/química , Insecticidas/toxicidad , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Testículo/efectos de los fármacos , Testículo/metabolismo , Espermatozoides/efectos de los fármacos , Espermatogénesis/efectos de los fármacos , Ratas Wistar , Testosterona , Caspasa 3/metabolismo , Caspasa 3/genética , Malondialdehído/metabolismo , Antioxidantes/farmacologíaRESUMEN
Particulate-based proliposomes were made by coating sucrose carrier particles with egg phosphatidylcholine (EPC), soya phosphatidylcholine (SPC) or soya phosphatidylcholine with an equimole ratio of cholesterol (SPC:Chol, 1:1). Inhalable multilamellar liposomes were generated from proliposomes in situ within a Pari LC Plus nebulizer by addition of aqueous phase, with no need for prior manual shaking. All proliposome formulations produced high aerosol and phospholipid outputs and were delivered in high fractions to the lower stage of a two-stage impinger. The SPC:Chol (1:1) liposomes tended to accumulate more in the nebulizer because of their greater rigidity, which correlated with the larger size measured at the end of nebulization. The size of aerosol droplets as measured by laser diffraction was similar for all formulations, however, at the sputtering period, the SPC:Chol (1:1) formulation produced large droplets with broadened size distribution. This study has demonstrated a simple approach to delivering high outputs of liposomes using a particulate-based proliposome technology and has shown an evidence of liposome generation from proliposomes within a medical nebulizer.
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Liposomas , Nebulizadores y Vaporizadores , Administración por Inhalación , Aerosoles , Rayos Láser , Microscopía Electrónica de TransmisiónRESUMEN
CONTEXT: The formulation of a new tablet is a time-consuming activity involving the preparation and testing of many different formulations with the aim of identifying one with the desired properties. In complex formulations it may not be clear which excipient is responsible for eliciting a particular property. OBJECTIVE: To investigate partial least squares (PLS) regression analysis of ATR-FTIR spectra of tablets as a predictive and investigative tool in the formulation of novel tablet formulations. MATERIALS: Magnesium stearate, lactose, acetylsalicylic acid and Ac-Di-Sol. RESULTS AND DISCUSSION: ATR-FTIR spectra of a simple aspirin tablet formulation with varying amounts of the lubricant magnesium stearate were obtained. PLS models were built using the spectral data as the multivariate variable and various physical properties of the tablets as the univariate variables. PLS models that allowed good predications to be made for samples not included in the training set were obtained for tablet hardness and disintegration time. It was clear from PLS model regression coefficients that magnesium stearate was responsible for the variation in the tablets' physical properties. CONCLUSION: PLS regression in combination with ATR-FTIR spectroscopy has been shown to be a useful approach for the prediction of the physical properties of tablets.
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Espectroscopía Infrarroja por Transformada de Fourier/métodos , Comprimidos/química , Análisis de los Mínimos Cuadrados , Modelos QuímicosRESUMEN
INTRODUCTION AND AIMS: The polyp detection rate (PDR) is defined as the percentage of colonoscopies in which one or more polyps are detected, and has been shown to be highly correlated with the adenoma detection rate. The aim of the present study was to evaluate the PDR at the Endoscopy Unit of the Kasr Al-Ainy Hospital, Cairo University, Egypt, through the i-SCAN, Endocuff, and underwater colonoscopy techniques. MATERIALS AND METHODS: The study was conducted on 100 Egyptian subjects over 50 years of age. Their polyp detection rate was measured through 4 different colonoscopic techniques. An equal number of patients were divided into 4 groups: i-SCAN, Endocuff, underwater colonoscopy, and controls. The control group was examined using standard white light colonoscopy. The colonoscopy evaluation included the type of agent utilized for bowel preparation, preparation grade, and colonoscopy withdrawal time. RESULTS: The general PDR was 48%. The i-SCAN technique had the highest rate (56%), followed by the underwater (52%) and the Endocuff (48%) techniques. CONCLUSION: The i-SCAN and underwater colonoscopy techniques produced higher PDR than the Endocuff-assisted and standard techniques, but with no statistical significance.
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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disorder commonly attributed to fatty acid deposition that can induce hepatic necroinflammation, defined as nonalcoholic steatohepatitis (NASH). It is strongly associated with obesity. Laparoscopic sleeve gastrectomy (LSG) is a favorable surgical modality for the treatment of morbid obesity. AIM: Our study evaluated the impact of LSG on patients with NAFLD and morbid obesity, 3 months after the operation, through clinical and biochemical characteristics, clinico-biochemical indices, and imaging parameters. PATIENTS AND METHODS: Morbidly obese patients with NAFLD±NASH underwent LSG. They were thoroughly evaluated clinically (body weight, body mass index, waist circumference) and biochemically (transaminases and triglycerides), as well as through the fatty liver index (FLI), the hepatic steatosis index (HSI), and ultrasound elastography imaging studies (liver stiffness measurement [LSM] and the controlled attenuation parameter [CAP]), before and 3 months after the LSG. RESULTS: Twenty-six obese patients with NAFLD underwent LSG that resulted in a significantly high reduction in all the parameters analyzed, except for liver transaminases. CONCLUSION: LSG is considered an efficient surgical modality for the treatment of morbidly obese patients with NAFLD.
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Disulfiram (DS), an anti-alcoholism medicine, shows strong anti-cancer activity in the laboratory, but the application in clinics for anti-cancer therapy has been limited by its prompt metabolism. Conventional liposomes have shown limited ability to protect DS. Therefore, the aim of this study is to develop PEGylated liposomes of DS for enhanced bio-stability and prolonged circulation. PEGylated liposomes were prepared using ethanol-based proliposome methods. Various ratios of phospholipids, namely: hydrogenated soya phosphatidylcholine (HSPC) or dipalmitoyl phosphatidylcholine (DPPC) and N-(Carbonyl-methoxypolyethylenglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-PEG2000) with cholesterol were used. DS was dissolved in the alcoholic solution in different lipid mol% ratios. The size of the resulting multilamellar liposomes was reduced by high-pressure homogenization. Liposomal formulations were characterized by size analysis, zeta potential, drug loading efficiency and stability in horse serum. Small unilamellar vesicles (SUVs; nanoliposomes) were generated with a size of approximately 80 to 120 nm with a polydispersity index (PDI) in the range of 0.1 to 0.3. Zeta potential values of all vesicles were negative, and the negative surface charge intensity tended to increase by PEGylation. PEGylated liposomes had a smaller size (80-90 nm) and a significantly lower PDI. All liposomes showed similar loading efficiencies regardless of lipid type (HSPC or DPPC) or PEGylations. PEGylated liposomes provided the highest drug biostability amongst all formulations in horse serum. PEGylated DPPC liposomes had t1/2 =77.3 ± 9.6 min compared to 9.7 ± 2.3 min for free DS. In vitro cytotoxicity on wild type and resistant colorectal cancer cell lines was evaluated by MTT assay. All liposomal formulations of DS were cytotoxic to both the wild type and resistant colorectal cancer cell lines and were able to reverse chemoresistance at low nanomolar concentrations. In conclusion, PEGylated liposomes have a greater potential to be used as an anticancer carrier for disulfiram.
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In this study, the effect of fluid physicochemical properties and the vibrating-mesh mechanism on the aerosols generated from vibrating-mesh nebulizers have been evaluated using fluids having a range of viscosity, surface tension and ion concentration. Two nebulizers were investigated: the Omron MicroAir NE-U22 (passively vibrating) and the Aeroneb Pro (actively vibrating) mesh nebulizers. For both devices, the total aerosol output was generally unaffected by fluid properties. Increased viscosity or ion concentration resulted in a decrease in droplet volume median diameter (VMD) and an increase in fine particle fraction (FPF). Moreover, increased viscosity resulted in prolonged nebulization and reduced output rate, particularly for the Omron nebulizer. Both nebulizers were unsuitable for delivery of viscous fluids since nebulization was intermittent or completely ceased at >1.92cP. The presence of ions reduced variability particularly for the Aeroneb Pro nebulizer. No clear effect of surface tension was observed on the performance of nebulizers employing a vibrating-mesh technology. However, when viscosity was low, reduced surface tension seemed advantageous in shortening the nebulization time and increasing the output rate, but for the Omron nebulizer this also increased the droplet VMD and decreased the FPF. This study has shown that vibrating-mesh nebulization was highly dependent on fluid characteristics and nebulizer mechanism of operation.
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Aerosoles/química , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Tensión Superficial , Vibración , ViscosidadRESUMEN
Multilamellar and oligolamellar liposomes were produced from ethanol-based soya phosphatidyl-choline proliposome formulations by addition of isotonic sodium chloride or sucrose solutions. The resultant liposomes entrapped up to 62% of available salbutamol sulfate compared with only 1.23% entrapped by conventionally prepared liposomes. Formulations were aerosolized using an air-jet nebulizer (Pari LC Plus) or a vibrating-mesh nebulizer (Aeroneb Pro small mesh, Aeroneb Pro large mesh, or Omron NE U22). All vibrating-mesh nebulizers produced aerosol droplets having larger volume median diameter (VMD) and narrower size distribution than the air-jet nebulizer. The choice of liposome dispersion medium had little effect on the performance of the Pari nebulizer. However, for the Aeroneb Pro small mesh and Omron NE U22, the use of sucrose solution tended to increase droplet VMD, and reduce aerosol mass and phospholipid outputs from the nebulizers. For the Aeroneb Pro large mesh, sucrose solution increased the VMD of nebulized droplets, increased phospholipid output and produced no effect on aerosol mass output. The Omron NE U22 nebulizer produced the highest mass output (approx. 100%) regardless of formulation, and the delivery rates were much higher for the NaCl-dispersed liposomes compared with sucrose-dispersed formulation. Nebulization produced considerable loss of entrapped drug from liposomes and this was accompanied by vesicle size reduction. Drug loss tended to be less for the vibrating-mesh nebulizers than the jet nebulizer. The large aperture size mesh (8 mum) Aeroneb Pro nebulizer increased the proportion of entrapped drug delivered to the lower stage of a twin impinger. This study has demonstrated that liposomes generated from proliposome formulations can be aerosolized in small droplets using air-jet or vibrating-mesh nebulizers. In contrast to the jet nebulizer, the performance of the vibrating-mesh nebulizers was greatly dependent on formulation. The high phospholipid output produced by the nebulizers employed suggests that both air-jet and vibrating-mesh nebulization may provide the potential of delivering liposome-entrapped or solubilized hydrophobic drugs to the airways.
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Albuterol/administración & dosificación , Broncodilatadores/administración & dosificación , Sistemas de Liberación de Medicamentos/métodos , Etanol/química , Profármacos/administración & dosificación , Aerosoles , Albuterol/química , Broncodilatadores/química , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Liposomas , Nebulizadores y Vaporizadores , Tamaño de la Partícula , Profármacos/químicaRESUMEN
BACKGROUND: During an environmental investigation of Pseudomonas aeruginosa in intensive care units, the liquid hand soap was found to be highly contaminated (up to 8 × 10(5)cfu/g) with this pathogen. It had been used over the previous five months and was probably contaminated during manufacturing. AIM: To evaluate the burden of this contamination on patients by conducting an epidemiological investigation using molecular typing combined with whole genome sequencing (WGS). METHODS: P. aeruginosa isolates from clinical specimens were analysed by double locus sequence typing (DLST) and compared with isolates recovered from the soap. Medical charts of patients infected with a genotype identical to those found in the soap were reviewed. WGS was performed on soap and patient isolates sharing the same genotype. FINDINGS: P. aeruginosa isolates (N = 776) were available in 358/382 patients (93.7%). Only three patients (0.8%) were infected with a genotype found in the soap. Epidemiological investigations showed that the first patient was not exposed to the soap, the second could have been exposed, and the third was indeed exposed. WGS showed a high number of core single nucleotide polymorphism differences between patients and soap isolates. No close genetic association was observed between soap and patient isolates, ruling out the hypothesis of transmission. CONCLUSION: Despite a highly contaminated soap, the combined investigation with DLST and WGS ruled out any impact on patients. Hand hygiene performed with alcohol-based solution for >15 years was probably the main reason. However, such contamination represents a putative reservoir of pathogens that should be avoided in the hospital setting.
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Microbiología Ambiental , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/aislamiento & purificación , Jabones , Genoma Bacteriano , Genotipo , Humanos , Tipificación Molecular , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/clasificación , Pseudomonas aeruginosa/genética , Análisis de Secuencia de ADN , Centros de Atención TerciariaRESUMEN
The aim of this study is to investigate using nanoemulsion formulations as drug-delivery vehicles of paclitaxel (PX), a poor water-soluble anticancer drug. Two commercially available nanoemulsion fat formulations (Clinoleic 20% and Intralipid 20%) were loaded with PX and characterised based on their size, zeta potential, pH and loading efficiency. The effect of formulation on the cytotoxicity of PX was also evaluated using MTT assay. The droplet size of the Clinoleic emulsion increased from 254.1nm to 264.7nm when paclitaxel (6mg/ml) was loaded into the formulation, compared to the drug-free formulation. Similarly, the droplet size of Intralipid increased from 283.3 to 294.6nm on inclusion of 6mg/ml paclitaxel. The Polydispersity Indexes (PDIs) of all the nanoemulsion formulations (Clinoleic and Intralipid) were less than 0.2 irrespective of paclitaxel concentration indicating that all nanoemulsion formulations used were homogeneously sized. The pH range for the Clinoleic formulations (7.1-7.5) was slightly higher than that of the Intralipid formulations (6.5-6.9). The zeta potential of linoleic had a greater negative value than that of Intralipid. Loading efficiencies for paclitaxel were 70.4-80.2% and 44.2-57.4% for Clinoleic and Intralipid formulations, respectively. Clinoleic loaded with paclitaxel decreased the viability of U87-MG cell to 6.4±2.3%, compared to Intralipid loaded with paclitaxel (21.29±3.82%). Both nanoemulsions were less toxic to the normal glial cells (SVG-P12), decreasing the cell viability to 25-35%. This study suggests that nanoemulsions are useful and potentially applicable vehicles of paclitaxel for treatment of glioma.
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Emulsiones/administración & dosificación , Emulsiones/química , Glioma/tratamiento farmacológico , Nanopartículas/administración & dosificación , Nanopartículas/química , Paclitaxel/administración & dosificación , Paclitaxel/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Línea Celular Tumoral , Química Farmacéutica/métodos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Excipientes/química , Humanos , Nutrición Parenteral/métodos , Tamaño de la Partícula , Fosfolípidos/química , Aceites de Plantas/química , Solubilidad , Aceite de Soja/químicaRESUMEN
This study aimed to evaluate the potential of a novel glycoside non-ionic surfactant synthesized and characterized in our laboratory for increased oral bioavailability of Cefixime. The surfactant was synthesized by simple etherification of bergenin with bromoundecane and characterized by (1)H NMR and mass spectroscopy (MS). Biocompatibility of the surfactant (BRM-BG) was assessed by in-vitro cytotoxicity against NIH/3T3 cells and human blood hemolysis. In-vivo acute toxicity was evaluated in mices. Cefixime loaded BRM-BG niosomes were investigated for drug entrapment efficiency using HPLC and surface morphology and vesicle size by atomic force microscopy (AFM) and dynamic light scattering (DLS). The in-vivo oral bioavailability and pharmacokinetics studies were carried out using rabbits. Cefixime loaded BRM-BG vesicles were spherical in the size range of 178.66±8.17nm with a polydipersity index (PDI) of 0.20±0.01, offering an entrapment efficiency as high as 78.4±0.83%. When the surfactant was applied on NIH 3T3 tissue culture, as high as 90.77±3.15% and 86.86±3.02%, cell viability at 1000µg/mL concentration after 24 and 48h respectively were observed. The surfactant also caused 5.49±1.62% haemolysis and was found to be safe at a dose up to 2000mg/kg. In-vivo drug plasma concentration (Cmax) was found to be 9.69±1.22µg/mL, much higher than that resulting from the intake of commercial suspension and capsules. BRM-BG demonstrated to be safe and effective as carrier of Cefixime following oral dosing in rabbits. The BRM-BG surfactant delivery nano-system is relatively safe and in animal models it is an appropriate carrier for Cefixime, offering enhanced bioavailability compared to commercially available formulations of the drug.
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Antibacterianos/administración & dosificación , Cefixima/administración & dosificación , Portadores de Fármacos/química , Tensoactivos/química , Administración Oral , Animales , Antibacterianos/farmacocinética , Benzopiranos/química , Disponibilidad Biológica , Cefixima/farmacocinética , Química Farmacéutica/métodos , Portadores de Fármacos/toxicidad , Dispersión Dinámica de Luz/métodos , Femenino , Glicósidos/química , Humanos , Liposomas , Masculino , Ratones , Microscopía de Fuerza Atómica/métodos , Células 3T3 NIH , Tamaño de la Partícula , Conejos , Tensoactivos/toxicidadRESUMEN
CONTEXT: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost. OBJECTIVE: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin. MATERIALS AND METHODS: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using 1HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method. RESULTS AND DISCUSSION: Findings showed that vesicles were able to entrap up to 67.82 ± 1.27% of the drug, and were rounded in shape with a size around 202.73 ± 5.30 nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500 mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug. CONCLUSION: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.
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Materiales Biocompatibles/química , Claritromicina/química , Claritromicina/metabolismo , Creatinina/química , Liposomas/química , Administración Oral , Animales , Disponibilidad Biológica , Línea Celular , Línea Celular Tumoral , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Estabilidad de Medicamentos , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Ratones , Células 3T3 NIH , Tamaño de la Partícula , Tensoactivos/químicaRESUMEN
CONTEXT: Vesicular systems have attracted great attention in drug delivery because of their amphiphilicity, biodegradability, non-toxicity and potential for increasing drug bioavailability. OBJECTIVE: A novel sugar-based double-tailed surfactant containing renewable block was synthesized for preparing niosomal vesicles that could be exploited for Levofloxacin encapsulation, aiming to increase its oral bioavailability. MATERIALS AND METHODS: The surfactant was characterized by 1H NMR, mass spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Its biocompatibility was studied against cell cultures and human blood hemolysis. In vivo acute toxicity was evaluated in mice. The vesicle morphology, size, drug-excipients interaction and entrapment efficiency (EE) were examined using atomic force microscope (AFM), dynamic light scattering (DLS), FT-IR and HPLC. Oral bioavailability studies of Levofloxacin in surfactant-based niosomal formulation were carried out using rabbits and plasma samples were analyzed using HPLC. RESULTS AND DISCUSSION: Vesicles were spherical in shape and the size was 190.31 ± 4.51 nm with a polydispersity index (PDI) of 0.29 ± 0.03. The drug EE in niosomes was 68.28 ± 3.45%. When applied on cell lines, high cell viability was observed even after prolonged exposure at high concentrations. It caused 5.77 ± 1.34% hemolysis at 1000 µg/mL and was found to be safe up to 2000 mg/kg. Elevated Levofloxacin plasma concentration was achieved when delivered with novel vesicles. CONCLUSION: The surfactant was demonstrated to be safe and effective as carrier of Levofloxacin. The study suggests that this sugar-based double-tailed nonionic surfactant could be promising nano-vesicular system for delivery and enhancing oral bioavailability of the hydrophobic Levofloxacin.
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Portadores de Fármacos/química , Levofloxacino/administración & dosificación , Levofloxacino/química , Liposomas/química , Nanopartículas/química , Administración Oral , Animales , Disponibilidad Biológica , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Química Farmacéutica/métodos , Sistemas de Liberación de Medicamentos/métodos , Excipientes/química , Femenino , Células HeLa , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Levofloxacino/metabolismo , Masculino , Ratones , Células 3T3 NIH , Nanopartículas/administración & dosificación , Tamaño de la Partícula , Tensoactivos/químicaRESUMEN
This study provided a convenient approach for large scale production of hydrogenated soya phosphatidylcholine nano-liposome powders using beclometasone dipropionate as a model drug and sucrose as proliposome carrier. Fluid-bed coating was employed to manufacture proliposomes by coating sucrose with the phospholipid (5%, 10%, 15% and 20% weight gains), followed by hydration, size reduction using high pressure homogenization, and freeze-drying to yield stable nano-vesicles. High pressure homogenization was compared with probe-sonication in terms of liposome size, zeta potential and drug entrapment. Furthermore, the effect of freeze-drying on vesicle properties generated using both size reduction methods was evaluated. Results have shown that high-pressure homogenization followed by freeze-drying and rehydration tended to yield liposomes smaller than the corresponding vesicles downsized via probe-sonication, and all size measurements were in the range of 72.64-152.50 nm, indicating that freeze-drying was appropriate, regardless of the size reduction technique. The liposomes, regardless of size reduction technique and freeze drying had slightly negative zeta potential values or were almost neutral in surface charge. The entrapment efficiency of BDP in homogenized liposomes was found to increase following freeze-drying, hence the drug entrapment efficiency values in rehydrated liposomes were 64.9%, 57%, 69.5% and 64.5% for 5%, 10%, 15% and 20% weight gains respectively. In this study, we have reported a reliable production method of nano-liposomes based on widely applicable industrial technologies such as fluid-bed coating, high pressure homogenization and freeze-drying. Moreover, sucrose played a dual role as a carrier in the proliposome formulations and as a cryoprotectant during freeze-drying.
Asunto(s)
Beclometasona/química , Fosfolípidos/química , Química Farmacéutica , Liofilización , Liposomas , Tamaño de la Partícula , Polvos , Sacarosa/químicaRESUMEN
AIM: The graphene oxide (GO) sheet has been considered one of the most promising carbon derivatives in the field of material science for the past few years and has shown excellent tumor-targeting ability, biocompatibility and low toxicity. We have endeavored to conjugate paclitaxel (PTX) to GO molecule and investigate its anticancer efficacy. MATERIALS & METHODS: We conjugated the anticancer drug PTX to aminated PEG chains on GO sheets through covalent bonds to get GO-PEG-PTX complexes. The tissue distribution and anticancer efficacy of GO-PEG-PTX were then investigated using a B16 melanoma cancer-bearing C57 mice model. RESULTS: The GO-PEG-PTX complexes exhibited excellent water solubility and biocompatibility. Compared with the traditional formulation of PTX (Taxol®), GO-PEG-PTX has shown prolonged blood circulation time as well as high tumor-targeting and -suppressing efficacy. CONCLUSION: PEGylated graphene oxide is an excellent nanocarrier for paclitaxel for cancer targeting.