Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. ...Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the body's immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided.
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Abstract We developed in this research a nanoparticle system for targeted drug delivery across the blood–brain barrier (BBB), which consists of the transferrin (Tf) conjugated nanoparticles of ...poly(lactide)- d -α-Tocopheryl polyethylene glycol succinate (PLA-TPGS) diblock copolymer. The NPs were prepared by the nanoprecipitation method and characterized for their various physicochemical and pharmaceutical properties. Cellular uptake and cytotoxicity of the Tf-conjugated PLA-TPGS NPs formulation of coumarin 6 as a model imaging agent or Docetaxel as a model drug were investigated in close comparison with those for the PLGA NPs formulation, the bare PLA-TPGS NPs formulation as well as with the clinical Taxotere® . The Tf-conjugated PLA-TPGS NPs formulation demonstrated great advantages over the other two NPs formulations and the original imaging/therapeutic agents. IC50 data showed that the Tf-conjugated PLA-TPGS NPs formulation of Docetaxel could be 23.4%, 16.9% and 229% more efficient than the PLGA NPs, the PLA-TPGS NPs formulations and Taxotere® after 24 h treatment, respectively. Moreover, our preliminary ex vivo biodistribution investigation demonstrated that although not as satisfactory, the Tf-conjugated PLA-TPGS NPs formulation could be able to deliver imaging/therapeutic agents across the BBB.
Paclitaxel drug delivery systems Zhang, Zhiping; Mei, Lin; Feng, Si-Shen
Expert opinion on drug delivery,
2013-March, 3/1/2013, 2013-Mar, 2013-03-00, 20130301, Letnik:
10, Številka:
3
Journal Article
Recenzirano
Introduction:
Paclitaxel (PTX) is one of the most effective broad-spectrum chemotherapeutic agents in the treatment of cancers. However, its clinical application has been limited due to its poor ...water solubility. Its current clinical administration uses the adjuvant of serious side effects and has undesired pharmacokinetics and biodistribution. There is, thus, a need for the development of alternate drug delivery systems of PTX to enhance its solubility, permeability and stability and further to promote a sustained, controlled and targeted delivery that will increase its therapeutic effects and reduce its side effects.
Areas covered:
This review is focused on recent developments of the various PTX delivery systems such as prodrugs, micelles, liposomes, solid lipid nanoparticles, nanoparticles of biodegradable polymers, dendrimers, nanohydrogels, as well as PTX-eluting stents.
Expert opinion:
Pharmaceutical nanotechnology can provide solutions to solve the problems encountered in drug formulation and drug delivery and may change the way drugs are made. The various nanocarriers could have high efficiency in drug encapsulation and cellular uptake, escape from elimination by microphages due to their appropriate size and surface modification and realize with ligand conjugation-targeted delivery.
Purpose
To analyze quality control in urodynamic studies, using a proportion control chart (p‐chart) for statistical process control.
Materials and Methods
This single‐center study was conducted at ...the Urodynamic Center of West China Hospital, Sichuan University. We randomly selected 15 samples from each month in 2020, and 180 urodynamic traces were finally enrolled. We used the p‐chart of statistical process control for analysis. We calculated the proportion of the incidence of a selected set of artefacts in the monthly urodynamic study process, including non‐standard zero setting, no cough test, incomplete records of all measurements by urodynamicists, catheter displacement, and baseline drift. Through the specific calculation formula of statistical process control, we obtained the values of the center line, lower control limit, and upper control limit.
Results
All data points of each artefact were within zone A. However, one outlier was found in the p‐chart of all artefacts in October, which might have been caused by inexperienced operators.
Conclusions
Statistical process control may play an important role in the process control of urodynamic studies and guide us in identifying the cause of poor quality in process management.
Abstract We developed a new strategy to prepare folate-decorated nanoparticles of biodegradable polymers for Quantum dots (QDs) formulation for targeted and sustained imaging for cancer diagnosis at ...its early stage. Poly(lactide)-vitamin E TPGS (PLA-TPGS) copolymer and vitamin E TPGS-carboxyl (TPGS-COOH) copolymer were synthesized. Their blend at various weight ratio was used to prepare folate-decorated nanoparticles (NPs) for QDs formulation to improve their imaging effects and reduce their side effects. The TPGS-COOH on the NP surface was designed to conjugate folate-NH2 with advantage to make the targeting effect adjustable. The size of such NPs was found in the range of 280–300 nm. In vitro cellular uptakes of such NPs were investigated with confocal laser scanning microscopy (CLSM), which demonstrated much higher internalization of the folate-decorated QDs-loaded PLA-TPGS/TPGS-COOH NPs by MCF-7 breast cancer cells which are of over-expression of folate receptors than the cellular uptake by NIH 3T3 fibroblast cells which are of low expression of folate receptors. Compared with the free QDs, the QDs formulated in the PLA-TPGS/TPGS-COOH NPs showed lower in vitro cytotoxicity for both of MCF-7 cells and NIH 3T3 cells. Additionally, our findings indicated that under same conditions, cytotoxicity of QDs formulated in the PLA-TPGS/TPGS-COOH NPs is lower for normal cells such as NIH 3T3 cells than that for breast cancer such as MCF-7 breast cancer cells due to folate targeting effect. Targeted imaging by QDs formulated in folate-decorated PLA-TPGS/TPGS-COOH nanoparticles with better effects and less side effects is feasible.
Abstract We developed a drug delivery system of herceptin-conjugated micelles, which consist of vitamin E TPGS and TPGS–siRNA conjugates, for targeted co-delivery of docetaxel and polo-like kinase 1 ...siRNA to achieve synergistic effects between the anticancer drug and the small interfering RNA responsible for multidrug resistance. The TPGS–siRNA conjugate is made through disulfide bond that could enable a pH-sensitive intracellular release. The load ratio between siPlk1 and docetaxel could be controlled by adjusting the siPlk1–TPGS to TPGS ratio as well as the drug to polymer ratio. NIH3T3, MCF7, and SK-BR-3 cell lines, which are of low, moderate and high HER2 overexpression, were employed to obtain proof-of-concept experimental results for the advantages of such a design. It has been shown that the IC50 , which is the drug concentration needed to kill 50% of the cancer cells in a designated time period, was 1.72, 0.042, 0.0032 and 0.000671 μg/mL for SK-BR-3 cells after 24 h treatment by Taxotere® , and docetaxel formulated in the TPGS micelles, the TPGS–siPlk1/TPGS micelles and the herceptin-conjugated TPGS–siPlk1/TPGS micelles, respectively.
Abstract The aim of this work was to develop an advanced theranostic micelles of D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), which are conjugated with transferrin for targeted ...co-delivery of docetaxel (DTX) as a model drug and ultra bright gold clusters (AuNC) as a model imaging agent for simultaneous cancer imaging and therapy. The theranostic micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, surface chemistry, drug encapsulation efficiency, drug loading and cellular uptake efficiency. Transferrin receptors expressing MDA-MB-231-luc breast cancer cells and NIH-3T3 fibroblast cells (control cells without transferrin receptor expression) were employed as an in vitro model to access cytotoxicity of the formulations. The overexpression of transferrin receptor on the surface of MDA-MB-231-luc cells was confirmed by flow cytometry. The biodistribution study and theranostic efficacy of the micelles were investigated by using the Xenogen IVIS® Spectrum imaging system, which includes AuNC based fluorescence imaging and luciferase induced bioluminescence imaging on MDA-MB-231-luc tumor bearing SCID mice. The IC50 values demonstrated that the non-targeted and targeted micelles could be 15.31 and 71.73 folds more effective than Taxotere® after 24 h treatment with the MDA-MB-231-luc cells. Transferrin receptor targeted delivery of such micelles was imaged in xenograft model and showed their great advantages for real-time tumor imaging and inhibition of tumor growth.
Abstract The aim of this work was to develop a new type of d -alpha-tocopheryl polyethylene glycol 1000 succinate mono-ester (TPGS) coated multi-functional (theranostic) liposomes, which contain both ...docetaxel and quantum dots (QDs) for cancer imaging and therapy. Non-targeting and folate receptor targeting TPGS coated theranostic liposomes were prepared by the solvent injection method and characterized for their particle size, polydispersity, zeta potential, surface chemistry and drug encapsulation efficiency. MCF-7 breast cancer cells of folate receptor overexpression were employed as an in vitro model to assess cellular uptake and cytotoxicity of the drug and QDs loaded liposomes. The mean particle size of the non-targeting and the targeting liposomes was found to be 202 and 210 nm, respectively. High resolution field emission transmission electron microscopy (FETEM) confirmed the presence of quantum dots in the peripheral hydrophobic membranes of the liposomes. The qualitative internalization of multi-functional liposomes by MCF-7 cells was visualized by confocal laser scanning microscopy (CLSM). The IC50 value, which is the drug concentration needed to kill 50% cells in a designated time period, was found to be 9.54 ± 0.76, 1.56 ± 0.19 and 0.23 ± 0.05 μg/ml for the commercial Taxotere® , non-targeting and targeting liposomes, respectively after 24 h culture with MCF-7 cells. The targeting multi-functional liposomes showed greater efficacy than the non-targeting liposomes and thus great potential to improve the cancer imaging and therapy.
This study evaluated cellular uptake of polymeric nanoparticles by using Caco-2 cells, a human colon adenocarcinoma cell line, as an in vitro model with the aim to apply nanoparticles of ...biodegradable polymers for oral chemotherapy. The feasibility was demonstrated by showing the localization and quantification of the cell uptake of fluorescent polystyrene nanoparticles of standard size and poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with polyvinyl alcohol (PVA) or vitamin E TPGS. Coumarin-6 loaded PLGA nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy (SEM) for surface morphology, zeta-potential for surface charge, and spectrofluorometry for fluorescent molecule release from the nanoparticles. The effects of particle size and particle surface coating on the cellular uptake of the nanoparticles were quantified by spectrofluorometric measurement. Cellular uptake of vitamin E TPGS-coated PLGA nanoparticles showed 1.4 folds higher than that of PVA-coated PLGA nanoparticles and 4-6 folds higher than that of nude polystyrene nanoparticles. Images of confocal laser scanning microscopy, cryo-SEM and transmission electron microscopy clearly evidenced the internalization of nanoparticles by the Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake. It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy.
Objectives
To establish the initial (before pressure equilibrium) and initial resting intravesical and abdominal pressure in the sitting position using air‐filled catheters, to assess the correlation ...between these pressures and obesity‐related measurements, and to estimate if obesity‐related measurements can be a guide to interpret initial and initial resting pressures in urodynamic testing.
Methods
Patients with non‐neurogenic lower urinary tract symptoms referred for urodynamic testing in our center were consecutively enrolled in a prospective study from August 2022 to October 2022. The correlation between the initial and initial resting pressures (before and after pressure equilibrium) and obesity‐related measurements were analyzed using Pearson's correlation coefficient and multiple linear regression analysis.
Results
Ninety‐eight patients aged 56 ± 16 were studied. The 95% range of the initial intravesical and abdominal pressure were 18–42 cmH2O and 21–60 cmH2O, respectively. The initial resting intravesical, abdominal, and detrusor pressure in the 95% range were 17–41, 16–42, and −5 to 4 cmH2O, respectively. Over the multiple analysis, abdominal fat thickness, and body mass index (BMI) correlated independently with initial intravesical pressure, and only visceral fat grade correlated with initial abdominal pressure. BMI correlated independently with initial resting intravesical pressure.
Conclusions
Our results determined the ranges of values of both initial and initial resting pressures in the air‐charged system. Meanwhile, the present study indicated the obesity‐related measurements may be used as a guide to interpret the initial and initial resting pressures in urodynamic testing, and may provide a reference for the quality control of these pressures.
