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1.
Curr Pharm Des ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38988170

ABSTRACT

Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Blood- -brain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

2.
Eur J Pharm Sci ; 185: 106425, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36934992

ABSTRACT

The drug nanosuspensions is a universal formulation approach for improved drug delivery of hydrophobic drugs and one the most promising approaches for increasing the biopharmaceutical performance of poorly water-soluble drug substances, especially for nature products. This review aimed to summarize the nanosuspensions preparation approaches and the main technological difficulties encountered in nanosuspensions development, such as guidelines for stabilizers screening, in vivo fate of the intravenously administrated nanosuspensions, and how to realize the intravenously target delivery was reviewed. Furthermore, challenges of nanosuspensions for the nature products delivery also was discussed and commented. Therefore, it hoped to provide reference and assistance for the nanosuspensions production, stabilizers usage, and predictability of in vivo fate and controllability of targeting delivery of the nature products nanosuspensions.


Subject(s)
Nanoparticles , Suspensions , Nanoparticles/chemistry , Technology, Pharmaceutical , Drug Delivery Systems , Technology , Solubility , Particle Size , Drug Compounding
3.
Article in English | MEDLINE | ID: mdl-36497911

ABSTRACT

Sex differences in emotion regulation strategies may impact sex differences in affective disorders. Using cognitive reappraisal strategy in the discriminative task of conditioned fear was studied to understand how sex differences in emotion regulation impact on conditioned fear in men and women. College students with low cognitive reappraisal scores completed the task of conditioned fear during two days: acquisition and extinction at the first day, and re-extinction at the second day. The reappraisal training was carried out before conditioned fear task. The self-reported fear rating of the conditioned stimulus (CS) and US-expectancy in the conditioned fear (unconditioned stimulus, US) were analyzed. Results showed all subjects acquired conditional fear and successfully distinguished CS+ from CS-. Cognitive reappraisal significantly reduces the fear rating and improves the extinction of US-expectancy in both sexes, but the fear rating in female reappraisal group decreases more slowly than that in male reappraisal group, as well as the extinction of US-expectancy in woman requiring a longer time and more trials of extinction than that in men. For individuals with low cognitive reappraisal scores, cognitive reappraisal promotes the extinction of conditioned fear in both males and females. Because of the original gender difference of conditioned fear extinction and emotion regulation, the effect of cognitive reappraisal on conditioned fear is complex, which shows differently in influence speed and practice effect.


Subject(s)
Extinction, Psychological , Fear , Female , Male , Humans , Fear/psychology , Extinction, Psychological/physiology , Sex Characteristics , Conditioning, Classical/physiology , Cognition/physiology
4.
J Nanosci Nanotechnol ; 20(6): 3598-3603, 2020 06 01.
Article in English | MEDLINE | ID: mdl-31748057

ABSTRACT

Spray-drying and freeze-drying are effective approaches to improve the long-term stability of nanosuspensions. This research explored the effect of spray-drying and freeze-drying techniques on PVP K30-stabilized silybin nanosuspensions. The morphology was observed by scanning electron microscopy (SEM): The spray-dried sample was spherical, and the freeze-dried samples were rodlike with smooth surfaces. The redispersibility was studied via dynamic light scattering (DLS): The size, PDI, and zeta of the spray-dried sample were 133.27 nm, 0.214, and 24.37 mV, respectively; the size, PDI, and zeta of the freeze-dried sample were 298.70 nm, 0.114, and 20.98 mV, respectively. The in vitro dissolution was studied, and the two dry powders showed a significant increase compared to silybin. The two dried powders had better long-term stability than the liquid starting material. Overall, spray-drying and freeze-drying are appropriate drying methods for the preparation of silybin nanosuspensions with better stability and dissolution velocity.

5.
Int J Pharm ; 572: 118768, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31669556

ABSTRACT

The strategy of formulating poorly soluble actives as liquid self-micro emulsifying drug delivery system (SMEDDS) has been explored in more than a thousand research papers. However, there have been a limited number of reports on pH sensitive solid SMEDDS. This study explored the feasibility of using poly (acrylic acid) modified mesoporous silica nanoparticles (MSNs-PAA) as a pH-mediated solid SMEDDS carrier for ß-elemene. This SMEDDS was optimized using a central composite design-response surface methodology, pseudo ternary phase diagrams, and studies of the preliminary stability. MSNs-PAA was synthesized and used for loading ß-elemene SMEDDS. Ele/MSNs-PAA was capable of pH-sensitive release of ß-elemene. In addition to structural analyses, the morphological and stability of this SMEDDS was also investigated. In comparison of the ß-elemene solution and the SMEDDS, the Ele/MSNs-PAA demonstrated improved Cmax, AUC and MRT after oral administration. These results suggested that the MSNs-PAA could be further developed as a promising approach for the pH sensitive release of ß-elemene SMEDDS with enhanced oral bioavailability.


Subject(s)
Acrylic Resins/chemistry , Drug Carriers/chemistry , Emulsions/chemistry , Nanoparticles/chemistry , Sesquiterpenes/chemistry , Silicon Dioxide/chemistry , Animals , Biological Availability , Drug Delivery Systems/methods , Hydrogen-Ion Concentration , Mice , Solubility/drug effects
6.
Carbohydr Polym ; 203: 356-368, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-30318224

ABSTRACT

Deacetyl mycoepoxydience (DM) nanocrystals core were stabilized by the folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG2000-FA) as the active-targeting stabilizer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as the reversion of multidrug resistance stabilizer, respectively. The DM nanocrystals was acted as the core and shelled by the polyethylene glycol-hyaluronic acid (PEG-HA). The optimal core-shell system demonstrated superior stability at 4 °C for 6 weeks by the stability study and higher dissolution velocity. Cytotoxicity in vitro and cell proliferation inhibition was evaluated by MCF-7 cells line. Furthermore, the core-shell nanocrystals revealed a concentration- and time-dependent cytotoxicity activity and enhanced the cell proliferation inhibition. Pharmacokinetic studies in rabbits showed core-shelled DM nanocrystals significantly increased AUC and t1/2 and reduced CLz compared to the DM solution for intravenous delivery. Results indicated that core-shell nanocrystals nanogel was successfully established with higher stability and the bioavailability of DM with higher safety was improved.

7.
Int J Biol Macromol ; 124: 667-680, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30502425

ABSTRACT

This study explored the feasibility of using smart nanocaged carrier technology for the delivering of multifunctional mPEG-chitosan stabilized silybin nanocrystals and to enhancing the long-term stability, dissolution velocity and bioavailability of the water insoluble drugs. The methoxypoly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-b-PCL), as nanocaged carrier, was modified with propargyl and azide group and confirmed by FTIR. The methoxypolythylene glycol-grafted chitosan (PEG-CS), as multifunctional stabilizer, were applied for the silybin nanocrystals formulation. Two silybin nanocrystals formulations (PEG-CS nanocrystals and nanocaged nanocrystals) were prepared using anti-solvent precipitation method and optimized by central composite design-response surface model. The transmission electron microscopy, scanning electron microscopy and atomic force microscope revealed small and uniformed morphology. The crystalline state of the nanocrystals was confirmed by X-ray powder diffraction and differential scanning calorimetry. The drug structure was confirmed by Fourier transform infrared spectroscopy. During the long term stability study, the nanocaged nanocrystals were presented remarkable stability. Compared with the silybin solution, the nanocaged nanocrystals and the PEG-CS nanocrystals drug delivery system also exhibited 5.54 and 2.58 fold increasing in the AUC, respectively. Thus, the nanocaged nanocrystals technology with excellent stability, improved dissolution velocity and relative bioavailability was recommended as an efficient and feasible approach for water insoluble drugs delivery.


Subject(s)
Chitosan/chemistry , Drug Carriers/chemistry , Drug Delivery Systems , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Silybin/administration & dosage , Silybin/pharmacokinetics , Administration, Oral , Animals , Biological Availability , Calorimetry, Differential Scanning , Hydrophobic and Hydrophilic Interactions , Male , Nanoparticles/ultrastructure , Particle Size , Rabbits , Solubility , Spectroscopy, Fourier Transform Infrared
8.
Curr Drug Deliv ; 15(9): 1221-1229, 2018.
Article in English | MEDLINE | ID: mdl-29779482

ABSTRACT

The poor penetration and low bioavailability are the main challenges for transdermal drug delivery. Nanocrystals technology is an attractive method for water-insoluble drug transdermal delivery, as the literature demonstrated that the penetration and bioavailability of the transdermal delivered water-insoluble drugs significantly enhanced and improved by the nanocrystals technology. Currently, the nanocrystals technology has been applied in transdermal delivery of cosmeceutical and for therapy of skin diseases, such as diclofenac acid, tretinoin and rutin. This review focused on the advantages of the nanocrystals technology for transdermal delivery. The special features of nanocrystals for the transdermal delivery of poorly soluble drugs are reviewed (skin disease treatment, safety and compliance, applying to cosmeceutical). Furthermore, the factors of influencing the nanocrystals penetration and the approaches of improving nanocrystals transdermal delivery are also discussed in detail.


Subject(s)
Drug Delivery Systems , Nanoparticles/chemistry , Nanotechnology , Pharmaceutical Preparations/chemistry , Skin Diseases/drug therapy , Water/chemistry , Administration, Cutaneous , Biological Availability , Pharmaceutical Preparations/administration & dosage , Solubility
9.
J Microencapsul ; 35(3): 241-248, 2018 May.
Article in English | MEDLINE | ID: mdl-29624090

ABSTRACT

Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6-8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.


Subject(s)
Antioxidants/chemistry , Excipients/chemistry , Freeze Drying/methods , Nanoparticles/chemistry , Quercetin/chemistry , Stilbenes/chemistry , Cryoprotective Agents/chemistry , Drug Stability , Folic Acid/analogs & derivatives , Nanoparticles/ultrastructure , Particle Size , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Resveratrol , Solubility , Suspensions , Vitamin E/chemistry
10.
J Nanosci Nanotechnol ; 18(6): 3850-3855, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29442718

ABSTRACT

A novel nanocrystal dispersible tablets was developed by apply quality by design (QbD) approach in this study. Following Deacetyl Mycoepoxydience (DM) nanosuspensions was prepared by antisolvent precipitation approach; the DM nanocrystal was solidified by freeze-drying method. Following the screening of cryoprotectants for solidification of the nanosuspensions, the physicochemical properties including re-dispersability, mean particle size (MPS), morphology and dissolution behavior of the DM nanocrystal was investigated. Experiment was designed with focus on the types and quantities of disintegrating agent during the DM nanocrystal dispersible tablets preparation. The DM nanocrystal-loaded dispersible tablets were produced using direct powder compression. Judging form the tablet disintegration time, central composite design (CCD) and response surface methodology was adopted to optimize disintegrating agent. In conclusion, the nanocrystal dispersible tablets approach was a reliable method for improving the dissolution and thereby the oral bioavailability of the DM in formulation development.

11.
J Nanosci Nanotechnol ; 18(8): 5207-5221, 2018 Aug 01.
Article in English | MEDLINE | ID: mdl-29458570

ABSTRACT

In the face of a large number of insoluble drugs, the development of nanocrystals is effective in destroying the limits of poorly soluble drug applications and becoming an indispensable route of drug delivery in the pharmaceutical industry. In addition, the proposed delivery goal is to provide more convenience and benefits and the number of researchers who are developing a number of advanced technologies try to use improved nano-drugs to improve the bioavailability of drug, drug dissolution velocity and solubility. Previously, more mature study has been done, for example, preparation of nanocrystals, the problems of safety, the route of administration and so on. This review systematically dwells upon several of the current nanocrystals technologies for target delivery by different modification technologies, such as magnetic nanocrystals, PEG and PEGylated chitosan modified nanocrystals, cationic nanocrystals and pluronic modified nanocrystals. Subsequently, the effects of surface charge and particle size on the drug targeted administration was analyzed. This review will provide a new insight for improving stability and controllability of the nanocrystals, and promote the nanocrystals technology development in targeting drug delivery.


Subject(s)
Drug Delivery Systems , Nanoparticles , Biological Availability , Particle Size , Pharmaceutical Preparations , Solubility
12.
Colloids Surf B Biointerfaces ; 160: 462-472, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-28988124

ABSTRACT

Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1H NMR. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5µM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53±18.36% and RSV-NB was 64.61±21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG-FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy.


Subject(s)
Folic Acid/chemistry , Lung Neoplasms/drug therapy , Nanoparticles/chemistry , Stilbenes/pharmacology , Xenograft Model Antitumor Assays , A549 Cells , Animals , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Survival/drug effects , Drug Delivery Systems/methods , Drug Stability , Humans , Lung Neoplasms/pathology , Mice, Inbred BALB C , Mice, Nude , Microscopy, Electron , Nanoparticles/ultrastructure , Phosphatidylethanolamines/chemistry , Polyethylene Glycols/chemistry , Resveratrol , Stilbenes/administration & dosage , Stilbenes/chemistry , Suspensions/chemistry
13.
J Nanosci Nanotechnol ; 17(1): 18-28, 2017 Jan.
Article in English | MEDLINE | ID: mdl-29616786

ABSTRACT

Nanocrystals technology for water insoluble drugs delivery has been expanding exponentially, as a robust approach, over the last ten years. Drug nanocrystals are sub-micron colloidal dispersion system of pure drug nanoparticles. Compared to the traditional pharmaceutical dosage forms, nano-crystals formulation presented many extraordinary properties such as enhanced dissolution rate and saturation solubility, high drug loading, excellent reproducibility of oral absorption, improved proportionality of dose-bioavailability, and increased patient compliance. This review explains the bioavailability improving mechanism in drug delivery to present the state-of-art nanocrystals. The physically stable nanocrystals with appropriate particle size and zeta potential could be prepared by screening of stabilizing agents. The marketed nanocrystal products and drug safety issues about the technology are also discussed. Moreover, the perspectives and challenges about improving nanocrystals investigated in this review could provide guidance for further study. Thus, this article could serve as a reference for optimizing the bioavailability of a specific drug candidate.


Subject(s)
Biological Availability , Drug Delivery Systems , Nanoparticles , Pharmaceutical Preparations/chemistry , Solubility
14.
Nanomedicine ; 13(2): 455-469, 2017 02.
Article in English | MEDLINE | ID: mdl-27558350

ABSTRACT

Nanosuspension technology is currently undergoing dramatic expansion in pharmaceutical science research and development. However, most of the research efforts generally focus on formulation and potential beneficial description, while the research into potential toxicological effects and implications (i.e., in vivo safety and health effects) is lacking. This review identifies some of the key factors for studying nanosuspension safety and the potential undesired effects related to nanosuspension exposure. The key factors for discussion herein include particle characterization, preparation approach, composition, and excipients of the formulation and sterilization methods. A few comments on the primary and required safety aspects of each administration route are also reviewed.


Subject(s)
Drug Delivery Systems , Nanoparticles , Chemistry, Pharmaceutical , Drug Stability , Excipients , Humans , Particle Size , Solubility , Suspensions
15.
Springerplus ; 5(1): 1676, 2016.
Article in English | MEDLINE | ID: mdl-27733978

ABSTRACT

BACKGROUND: Early onset peritonitis (EOP) is not uncommon in peritoneal dialysis patients. We aimed to compare the prognosis of EOP and non-EOP peritoneal dialysis patients. METHODS: This study included subjects that underwent PD from January 1, 2004 to July 31, 2013. Patient characteristics were collected. EOP was defined as peritonitis occurring within 6 months after initiation of PD. Patient and technique survival were compared between EOP and non-EOP patients using Cox regression analyses. RESULTS: In total, 189 subjects were included in this study. Patients were divided into EOP (n = 55) and non-EOP groups (n = 134). There was no significant difference in the causative organisms of peritonitis between the two groups. After adjusting for age, diabetes status, serum albumin level and residual renal function, the multivariable Cox regression model revealed that EOP was an independent risk factor for patient mortality (HR 2.03, RI 1.09-3.80, p = 0.026), technique failure (HR 1.69, RI 1.12-2.87, p = 0.015) and total survival (HR 1.73, RI 1.12-2.68, p = 0.013). CONCLUSIONS: EOP was identified as an independent risk factor for mortality and technique failure in peritoneal dialysis patients.

16.
Carbohydr Polym ; 153: 471-481, 2016 Nov 20.
Article in English | MEDLINE | ID: mdl-27561519

ABSTRACT

Here a series of multifunctional stabilizers was designed and used in a nanosuspension stability enhancement study. Methoxypolyethylene glycol (M PEG)-grafted chitosan, accompanied by space steric hindrance, an electrostatic repulsion function, and a solvation effect, is a multifunctional stabilizer. Deacetyl mycoepoxydience (DM) nanosuspension was prepared using the anti-solvent precipitation approach. The effects of the DM and the multifunctional stabilizer concentration, solvent to anti-solvent ratio, crystallization and storage temperature, and ultrasonic time on drug particle formation during the anti-solvent processing were investigated and the nanosuspension stability was studied. The nanosuspension showed dendritic-like nanostructures and a crystalline state in a morphology and crystalline state study. The optimized drug and multifunctional stabilizer concentration range were selected through the response surface optimization method. The most appropriate and stable nanosuspension could be obtained through the optimal parameters. This study demonstrated that M PEG-grafted chitosan (M PEGC) could be used as a multifunctional stabilizer to control particle size and improve nanosuspension stability.


Subject(s)
Antineoplastic Agents/administration & dosage , Bridged-Ring Compounds/administration & dosage , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Pyrones/administration & dosage , Antineoplastic Agents/chemistry , Bridged-Ring Compounds/chemistry , Colloids/chemistry , Drug Stability , Excipients/chemistry , Nanoparticles/ultrastructure , Particle Size , Pyrones/chemistry , Solubility
17.
J Environ Sci (China) ; 42: 168-177, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27090708

ABSTRACT

A series of CeO2-ZrO2-WO3 (CZW) catalysts prepared by a hydrothermal synthesis method showed excellent catalytic activity for selective catalytic reduction (SCR) of NO with NH3 over a wide temperature of 150-550°C. The effect of hydrothermal treatment of CZW catalysts on SCR activity was investigated in the presence of 10% H2O. The fresh catalyst showed above 90% NOx conversion at 201-459°C, which is applicable to diesel exhaust NOx purification (200-440°C). The SCR activity results indicated that hydrothermal aging decreased the SCR activity of CZW at low temperatures (below 300°C), while the activity was notably enhanced at high temperature (above 450°C). The aged CZW catalyst (hydrothermal aging at 700°C for 8 hr) showed almost 80% NOx conversion at 229-550°C, while the V2O5-WO3/TiO2 catalyst presented above 80% NOx conversion at 308-370°C. The effect of structural changes, acidity, and redox properties of CZW on the SCR activity was investigated. The results indicated that the excellent hydrothermal stability of CZW was mainly due to the CeO2-ZrO2 solid solution, amorphous WO3 phase and optimal acidity. In addition, the formation of WO3 clusters increased in size as the hydrothermal aging temperature increased, resulting in the collapse of structure, which could further affect the acidity and redox properties.


Subject(s)
Ammonia/chemistry , Cerium/chemistry , Models, Chemical , Nitrogen/chemistry , Oxides/chemistry , Oxygen/chemistry , Tungsten/chemistry , Zinc Oxide/chemistry , Catalysis , Oxidation-Reduction
18.
Cardiorenal Med ; 6(2): 150-8, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26989400

ABSTRACT

OBJECTIVE: Patients with end-stage renal disease are susceptible to cardiac valve calcification (CVC) due to mineral metabolism disorders and other factors. The purpose of this study was to investigate the risk factors for new-onset CVC in patients on maintenance peritoneal dialysis (PD). METHODS: This study included patients who underwent PD catheter insertion from January 2006 to June 2013 in our Peritoneal Dialysis Center. Clinical data were collected on CVC status during echocardiography evaluations (twice) at an interval of >6 months. The data collected included intact parathyroid hormone, C-reactive protein (CRP), serum phosphorus (P), serum calcium (Ca), albumin (Alb), prealbumin and the use of five types of antihypertensive drugs, statins, active vitamin D3 and Ca tablets. RESULTS: In total, 194 patients - 105 (54.1%) men, average age 60.5 ± 13.0 years - were included. CVC was present in 50 (25.8%) patients during PD catheter placement. After an average PD duration of 20.9 ± 10.4 months, CVC was detected in 97 patients (50.0%). New-onset CVC was found in 62 patients (32.0%). Multivariate logistic regression analysis revealed that only serum P levels (p = 0.01, OR = 2.569), Alb levels (p = 0.04, OR = 0.935), dialysis duration (p = 0.03, OR = 1.039) and CRP levels (p = 0.02, OR = 1.031) were associated with CVC. CONCLUSION: Serum P, Alb and CRP levels as well as dialysis duration are independent risk factors for CVC.

19.
Int J Pharm ; 495(2): 738-49, 2015 Nov 30.
Article in English | MEDLINE | ID: mdl-26383838

ABSTRACT

In recent years, nanosuspension has been considered effective in the delivery of water-soluble drugs. One of the main challenges to effective drug delivery is designing an appropriate nanosuspension preparation approach with low energy input and erosion contamination, such as the bottom-up method. This review focuses on bottom-up technologies for preparation of nanosuspensions. The features and advantages of drug nanosuspension, including bottom-up methods as well as the corresponding characterization techniques, solidification methods, and drug delivery dosage forms, are discussed in detail. Certain limitations of commercial nanosuspension products are also reviewed.


Subject(s)
Drug Delivery Systems , Nanoparticles , Pharmaceutical Preparations/administration & dosage , Drug Design , Pharmaceutical Preparations/chemistry , Solubility , Suspensions , Technology, Pharmaceutical/methods , Water/chemistry
20.
Int J Pharm ; 494(1): 479-89, 2015 Oct 15.
Article in English | MEDLINE | ID: mdl-26302857

ABSTRACT

The present study was aimed at tailoring the particle size of ursolic acid (UA) nanosuspension for improved anticancer activity. UA nanosuspensions were prepared by antisolvent precipitation using a four-stream multi-inlet vortex mixer (MIVM) under defined conditions of varying solvent composition, drug feeding concentration or stream flow rate. The resulting products were characterized for particle size and polydispersity. Two of the UA nanosuspensions with mean particle sizes of 100 and 300 nm were further assessed for their in-vitro activity against MCF-7 breast cancer cells using fluorescence microscopy with 4',6-diamidino-2-phenylindole (DAPI) staining, as well as flow cytometry with propidium (PI) staining and with double staining by fluorescein isothiocyanate. It was revealed that the solvent composition, drug feeding concentration and stream flow rate were critical parameters for particle size control of the UA nanosuspensions generated with the MIVM. Specifically, decreasing the UA feeding concentration or increasing the stream flow rate or ethanol content resulted in a reduction of particle size. Excellent reproducibility for nanosuspension production was demonstrated for the 100 and 300 nm UA preparations with a deviation of not more than 5% in particle size from the mean value of three independent batches. Fluorescence microscopy and flow cytometry revealed that these two different sized UA nanosuspensions, particularly the 300 nm sample, exhibited a higher anti-proliferation activity against the MCF-7 cells and afforded a larger population of these cells in both early and late apoptotic phases. In conclusion, MIVM is a robust and pragmatic tool for tailoring the particle size of the UA nanosuspension. Particle size appears to be a critical determinant of the anticancer activity of the UA nanoparticles.


Subject(s)
Antineoplastic Agents/chemistry , Chemical Precipitation , Nanoparticles/chemistry , Particle Size , Suspensions/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Cycle/drug effects , Drug Stability , Female , Humans , MCF-7 Cells , Microscopy, Electron, Transmission , Reproducibility of Results , Solubility , Solvents/chemistry , Surface Properties , Suspensions/pharmacology , Ursolic Acid
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