[Current status and prospect of translational medicine in nanotechnology].

Nowadays, nanotechnologies have shown wide application foreground in the biomedical field of medicine laboratory tests, drug delivery, gene therapy and bioremediation. However, in recent years, nanomaterials have been labeled poisonous, because of the disputes and misunderstandings of mainstream views on their safety. Besides, for the barriers of technical issues in preparation like: (1) low efficacy (poor PK & PD and low drug loading), (2) high cost (irreproducibility and difficulty in scale up), little of that research has been successfully translated into commercial products. Currently, along with the new theory of "physical damage is the origin of nanotoxicity", biodegradability and biocompatibility of nanomaterials are listed as the basic principle of safe application of nanomaterials. Combining scientific design based on molecular level with precision control of process engineering will provide a new strategy to overcome the core technical challenges. New turning point of translational medicine in nanotechnology may emerge.

Sensitive electrochemical flow injection analysis of H2O2 released from cells with a pass-through mode.

Conventional plate electrodes were commonly used in electrochemical flow injection analysis and only part of molecules diffused to the plane of electrodes could be detected, which would limit the performance of electrochemical detection. In this study, a low-cost native stainless steel wire mesh (SSWM) electrode was integrated into a 3D-printed device for electrochemical flow injection analysis with a pass-through mode, which is different compared with previous flow-through mode. This strategy was applied for sensitive analysis of hydrogen peroxide (H2O2) released from cells. Under the optimal conditions (the applied potentials, the flow rate and the sample volume), the device exhibits high sensitivity toward H2O2. Linear relationships could be achieved between electrochemical responses and the concentration of H2O2 ranging from 1 nM to 1 mM. The excellent analytical performance of the SSWM-based device could be attributed to the pass-through mode based on the mesh microstructure and intrinsic catalytic properties for H2O2 by stainless steel. This approach could be further successfully extended for screening of H2O2 released from HeLa cells with electrochemical responses linear to the number of cells in a range of 3 - 1.35 × 104 cells with an injection volume of 30 µL. This study revealed the potential of mesh electrodes in electrochemical flow injection analysis for cellular function and pathology and its possible extension in cell counting and on-line analysis.

Effect of an extrafibrillar dentin demineralization strategy on the durability of the resin-dentin bond.

OBJECTIVES: This study aimed to evaluate the potential of the extrafibrillar dentin demineralization strategy on the long-term dentin bond strength of an etch-and-rinse adhesive. METHODS: A water-soluble glycol chitosan-EDTA (GCE), a chelating conditioner, was synthesized and subjected to size-exclusion dialysis to obtain molecules >40 kDa. The conjugation of EDTA to glycol chitosan was analyzed by Fourier transform infrared (FTIR) spectroscopy. Mid-coronal dentin surfaces of 80 teeth were either acid-etched with 35% phosphoric acid or conditioned with 25 mg/mL GCE (n = 40) and thoroughly water-sprayed before applying the etch-and-rinse adhesive Adper Single Bond Plus and placing Z250 composite resin (3 M Oral Care; St Paul, MN, USA). Resin-bonded specimens were prepared into beams with a cross-sectional area of about 0.9 mm2 vertically through the resin-dentin interfaces before the microtensile bond strengths (MTBS) were determined immediately or after 3, 6, or 12 months of water storage. The resin-dentin interfaces were analyzed using transmission electron microscopy (TEM). The MTBS data were analyzed using two-way ANOVA followed by the LSD post-hoc multiple comparisons (P < 0.05). RESULTS: FTIR spectra showed that EDTA was successfully conjugated to glycol chitosan. The phosphoric acid-etching group and GCE-conditioning group showed similar bond strength values after 24 h of water storage. The bond strength of the phosphoric acid-etching group after 12-month water aging was significantly reduced from 51.61 ± 3.30 MPa to 38.57 ± 4.81 MPa, while the bond strength of the GCE-conditioning group was not significantly reduced from 50.28 ± 3.62 MPa to 46.40 ± 4.71 MPa.The degradation of the hybrid layer could be detected in the phosphoric acid-etching group after 12 months of water aging, but not in the GCE-conditioning group. CONCLUSION: The extrafibrillar dentin demineralization strategy using GCE conditioner could defy the hybrid layer degradation of the dentin bond after 12 months of water aging and enhance the dentin bond durability of the etch-and-rinse adhesive Adper Single Bond Plus.

Conjugation of quantum dots with graphene for fluorescence imaging of live cells.

It is difficult to achieve fluorescent graphene-quantum dots (QDs) conjugation because graphene quenches the fluorescence of the QDs. In the present study, the conjugation of graphene (reduced graphene oxide, RGO) with QDs via a bridge of bovine serum albumin (BSA) provides a novel highly fluorescent nano probe for the first time. BSA capped QDs are firmly grafted onto polyethylenimine (PEI)/poly(sodium 4-styrenesulfonate) (PSS) coated RGO (graphene-QDs) via electrostatic layer by layer assembly. The strong luminescence of the graphene-QDs provides a potential for non-invasive optical in vitro imaging. The graphene-QDs are used for in vitro imaging of live human carcinoma (Hela) cells. Graphene-QDs could be readily up-taken by Hela cells in the absence of specific targeting molecules, e.g., antibodies or folic acid, and no in vitro cytotoxicity is observed at 360 µg mL(-1) of the graphene-QDs. The results for the imaging of live cells indicated that the cell-penetrating graphene-QDs could be a promising nano probe for intracellular imaging and therapeutic applications.

Effect of altered temperature storage on the in vitro cellular uptake of liposome drug products.

The aim of this study was to evaluate whether temperature stress conditions affect the cellular uptake of liposomal doxorubicin, Doxil (DXL; Ortho Biotech, Raritan, New Jersey, USA), and liposomal daunorubicin, DaunoXome (DXM; Gilead Sciences, San Dimas, California, USA). Uptake of these cytotoxic compounds is essential for their pharmacological effect. Commercially available DXL and DXM were stressed for 6 days under altered temperature conditions of 22 and 50 degrees C, as compared to storage in their buffered formulations at the labeled temperature of 4 degrees C. The cellular uptake of the liposomal drugs was measured by fluorescence intensity in human ovarian SKOV-3 and murine macrophage J774A.1 cell lines following a 4-hour exposure to DXL or DXM. There was a 5- to 10-fold increase in the cellular uptake of DXL and DXM in both cell lines after stress exposure to 50 degrees C. Exposure of DXL to 22 degrees C stress decreased its uptake by SKOV-3 cells, when compared to exposure of DXL to 4 degrees C control conditions. A cell-based uptake assay may provide a means to assess changes in the functional activity of liposomes in conjunction with evaluation of their physicochemical properties in order to evaluate the stability and integrity of liposomes.

The evolving landscape of drug products containing nanomaterials in the United States.

The Center for Drug Evaluation and Research (CDER) within the US Food and Drug Administration (FDA) is tracking the use of nanotechnology in drug products by building and interrogating a technical profile of products containing nanomaterials submitted to CDER. In this Analysis, data from more than 350 products show an increase in the submissions of drug products containing nanomaterials over the last two decades. Of these, 65% are investigational new drugs, 17% are new drug applications and 18% are abbreviated new drug applications, with the largest class of products being liposomal formulations intended for cancer treatments. Approximately 80% of products have average particle sizes of 300 nm or lower. This analysis identifies several trends in the development of drug products containing nanomaterials, including the relative rate of approvals of these products, and provides a comprehensive overview on the landscape of nanotechnology application in medicine.

Assuring quality and performance of sustained and controlled release parenterals: EUFEPS workshop report.

This is a summary report of the workshop, organized by the European Federation of Pharmaceutical Scientists in association with the American Association of Pharmaceutical Scientists, the European Agency for the Evaluation of Medicinal Products, the European Pharmacopoeia, the US Food and Drug Administration and the United States Pharmacopoeia, on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals" held in Basel, Switzerland, February 2003. Experts from the pharmaceutical industry, regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals, and identify critical process parameters and their control. This workshop was a follow-up workshop to a previous workshop on Assuring Quality and Performance of Sustained and Controlled Release Parenterals that was held in Washington, DC in April 2001. This report reflects the outcome of the Basel 2003 meeting and the advances in the field since the Washington, DC meeting in 2001. As necessary, the reader is referred to the report on the 2001 meeting. Areas were identified at the 2003 Basel meeting where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops and meetings.

Assuring quality and performance of sustained and controlled release parenterals: workshop report.

This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia co-sponsored workshop on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals." Experts from the pharmaceutical industry, the regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals and identify critical process parameters and their control. Areas were identified where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops, meetings and working groups in this area.

A case of mimicking angioedema: chin silicone granulomatous reaction spreading all over the face after receiving liquid silicone injection forty years previously.

Liquid injectable silicone has been used for soft tissue augmentation for five decades. Many complications following liquid silicone injection have been reported. To diagnose and manage silicone granuloma remains difficult. Silicone granuloma must be diagnosed with the history of liquid silicone injection and the histology of tissue biopsy. We presented a case of granulomatous reaction after the injection of liquid silicone for chin augmentation forty years ago, causing total facial swelling, which mimicking angioedema initially. We administered methylprednisolone to the patient. Initial response to methylprednisolone was favorable.

Functionalization of MWNTs with hyperbranched PEI for highly selective isolation of BSA.

Cationic hyperbranched BPEI was immobilized on the surface of MWNTs via electrostatic interactions between the positively charged protonated amines within the polymer and the carboxyl groups on the chemically oxidized MWNT surface. The functionalized BPEI-MWNTs were characterized by FT-IR, TGA, TEM and surface charge analysis, and it was used as a bio-sorbent for the adsorption of proteins. CD spectra showed no conformational change of BSA during the adsorption/desorption process. A dynamic adsorption capacity of 167 mg · g⁻¹ for BSA was achieved. With a sample volume of 2.0 mL, an enrichment factor of 10 was obtained along with an adsorption efficiency of 100%, a recovery of 100%, a sampling frequency of 10 h⁻¹ and a RSD of 2.6% at 25 µg · mL⁻¹ BSA.

Evaluation of substrates for 90 degrees peel adhesion--a collaborative study. II. Transdermal drug delivery systems.

In a previous study on peel adhesion for medical tapes, it was shown that a stainless steel (SS) substrate better discriminated among medical tapes than a high-density polyethylene (HDPE) substrate. The objective of this study was to determine if a SS substrate would also better distinguish among transdermal drug delivery systems (TDDSs). Five TDDSs (Vivelle Dot, Climara, Catapres-TTS, Duragesic, and Mylan Fentanyl) were evaluated on three different substrates (SS, HDPE, and human cadaver skin). All measurements were made using a dwell time of approximately 3 min, a peel angle of 90 degrees, and a peel speed of 300 mm/min. Differences among TDDSs were greater for SS than for HDPE, using the F statistic for testing for differences among TDDSs means as a measure of heterogeneity, thereby indicating greater discrimination by SS.

Evaluation of substrates for 90 degrees peel adhesion--a collaborative study. I. Medical tapes.

As part of a method development for peel testing, an interlaboratory comparison among Food and Drug Administration-Center for Drug Evaluation and Research, Food and Drug Administration-Center for Devices and Radiological Health and Southwest Research Institute was conducted using medical tapes. The aim was to determine which readily available substrate [stainless steel (SS), high density polyethylene (HDPE) or Vitro-Skin(R)] would best distinguish among various medical tapes. Five medical tapes (3M 1523, 3M 1525L, 3M 1776, Mepiform(R) and Mediderm(R) 3505) were evaluated on four different substrates (SS, HDPE, Vitro-Skin, and human cadaver skin) using the following peel parameters: approximately 3 min dwell time, 90 degrees peel angle, and 300 mm/min peel rate. No substrate mimics cadaver skin for all five tapes. SS had the best ability to distinguish among the medical tapes. Overall, for quality control purposes (yielding good discrimination and precision), SS would be the optimal substrate.