High dose, dual-release polymeric films for extended surgical bed paclitaxel delivery.

While surgery represents a major therapy for most solid organ cancers, local recurrence is clinically problematic for cancers such as sarcoma for which adjuvant radiotherapy and systemic chemotherapy provide minimal local control or survival benefit and are dose-limited due to off-target side effects. We describe an implantable, biodegradable poly(1,2-glycerol carbonate) and poly(caprolactone) film with entrapped and covalently-bound paclitaxel enabling safe, controlled, and extended local delivery of paclitaxel achieving concentrations 10,000× tissue levels compared to systemic administration. Films containing entrapped and covalently-bound paclitaxel implanted in the tumor bed, immediately after resection of human cell line-derived chondrosarcoma and patient-derived xenograft liposarcoma and leiomyosarcoma in mice, improve median 90- or 200-day recurrence-free and overall survival compared to control mice.

Synthesis of Polyethylene Glycol-Poly(glycerol carbonate) Block Copolymeric Micelles as Surfactant-Free Drug Delivery Systems.

We report the synthesis of block copolymers of monomethoxylated polyethylene glycol and poly(glycerol carbonate) (mPEG--PGC) via the ring-opening polymerization of benzyl glycidyl ether, monomethoxylated polyethylene glycol, and carbon dioxide using a cobalt salen catalyst. The resulting block copolymers display high polymer/cyclic carbonate selectivity (>99%) and, if two oxirane monomers are used, random incorporation into the polymer feed. The resulting diblock mPEG--PGC polymer shows promise as a nanocarrier for surfactant-free, sustained chemotherapeutic delivery.

Access to the Enantiopure Axially Chiral Cyclophane Isoplagiochin D through Atropo-diastereoselective Heck Coupling.

Macrocyclization is typically the key step in the syntheses of cyclophane-type natural products. Considering cyclophanes with axially chiral biaryl moieties, the control of atroposelectivity is essential with biological activity and is synthetically challenging. We report an atroposelective approach involving Heck cyclization, which for the first time enables the total synthesis of an enantiopure macrocyclic bis(bibenzyl), namely isoplagiochin D.

Evaluation of the Active Targeting of Melanin Granules after Intravenous Injection of Dendronized Nanoparticles.

The biodistribution of dendronized iron oxides, NPs10@D1_DOTAGA and melanin-targeting NPs10@D1_ICF_DOTAGA, was studied in vivo using magnetic resonance imaging (MRI) and planar scintigraphy through [Lu]Lu-radiolabeling. MRI experiments showed high contrast power of both dendronized nanoparticles (DPs) and hepatobiliary and urinary excretions. Little tumor uptake could be highlighted after intravenous injection probably as a consequence of the negatively charged DOTAGA-derivatized shell, which reduces the diffusion across the cells' membrane.

How a grafting anchor tailors the cellular uptake and in vivo fate of dendronized iron oxide nanoparticles.

Superparamagnetic spherical iron oxide nanoparticles of 10 nm diameter have been synthesized by thermal decomposition and grafted through a direct ligand exchange protocol with two dendrons bearing respectively a monophosphonic anchor (D2) or a biphosphonic tweezer (D2-2P) at their focal point. Physico-chemical characterization techniques such as dynamic light scattering (DLS), zeta potential, Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and superconducting quantum interference device (SQUID) magnetometry were used to assess their composition, colloidal stability and magnetic properties. High-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectroscopy studies have been conducted to understand the organic shell composition and to determine both the grafting rate of the dendrons onto the nanoparticle surface and the influence of the remaining oleic acid originating from the synthesis protocol on the cellular uptake.

Design of iron oxide-based nanoparticles for MRI and magnetic hyperthermia.

Iron oxide nanoparticles are widely used for biological applications thanks to their outstanding balance between magnetic properties, surface-to-volume ratio suitable for efficient functionalization and proven biocompatibility. Their development for MRI or magnetic particle hyperthermia concentrates much of the attention as these nanomaterials are already used within the health system as contrast agents and heating mediators. As such, the constant improvement and development for better and more reliable materials is of key importance.

Preparation of core/shell NaYF:Yb,Tm@dendrons nanoparticles with enhanced upconversion luminescence for in vivo imaging.

Upconverting nanoparticles (UCNPs) were successfully dendronized for fluorescence medical imaging applications. The structural and morphological characterizations of resulting core/shell NaYF:Yb,Tm@dendrons nanoparticles were performed by means of X-ray diffraction, infrared spectroscopy and transmission electron microscopy. In vitro cytotoxicity assays have evidenced their low toxicity.

Dendrimer-nanoparticle conjugates in nanomedicine.

Nanomedicine can take advantage of the recent developments in nanobiotechnology research areas for the creation of platforms with superior drug carrier capabilities, selective responsiveness to the environment, unique contrast enhancement profiles and improved accumulation at the disease site. Colloidal inorganic nanoparticles (NPs) have been attracting considerable interest in biomedicine, from drug and gene delivery to imaging, sensing and diagnostics. It is essential to modify the NPs surface to have enhanced biocompatibility and reach multifunctional systems for the in vitro and in vivo applications, especially in delivering drugs locally and recognizing overexpressed biomolecules.

A new classification of glaucomas.

Purpose: To suggest a new glaucoma classification that is pathogenic, etiologic, and clinical.

Methods: After discussing the logical pathway used in criteria selection, the paper presents the new classification and compares it with the classification currently in use, that is, the one issued by the European Glaucoma Society in 2008.

Results: The paper proves that the new classification is clear (being based on a coherent and consistently followed set of criteria), is comprehensive (framing all forms of glaucoma), and helps in understanding the sickness understanding (in that it uses a logical framing system).

Critical analysis of the classification of glaucomas issued by the European Glaucoma Society in 2008.

Purpose: To critically analyze the 2008 European Glaucoma Society classification of glaucomas, in order to reveal its advantages and shortcomings.

Methods: The paper tries to determine the extent to which this classification is clear (being based on a coherent and consistently followed set of criteria), is comprehensive (framing all forms of glaucoma), helps to understand the sickness (using a logical framing system), and facilitates therapeutic decision making (offering direct therapeutic suggestions).

Results And Conclusion: The paper shows that, compared with all the previous classifications, the 2008 European Glaucoma Society classification is one step ahead (in the way of classifying the group of secondary angle-closure glaucomas), two steps behind (in rejecting two useful categories of congenital glaucoma), and similar in several respects: that it is based on criticizable fundamental and secondary criteria that cannot cover all forms of sickness gathered at a particular crossing; that it uses several equally weighted criteria for one single crossing (division); that it frames one clinical entity in several clinical categories; that it does not reflect reality in some aspects; and that it does not offer direct therapeutic suggestions: after framing a case in a scheme built on the basis of gonioscopic observation, it requires a second stage of pathogenic analysis, so that the ophthalmologist is able to decide the correct treatment only in the third stage.

[Criticism of the gonioscopic classifications of the glaucoma: with particular reference to the classification issued by the European Glaucoma Society in 2008].

Purpose: To critically analyze the gonioscopic classifications of glaucoma, especially of the classification issued by the European Glaucoma Society in 2008, in order to reveal its advantages and shortcomings.

Methods: The paper tries to determine the extent to which this classification is clear (being based on a coherent and consistently followed set of criteria), is comprehensive (framing all forms of glaucoma), helps to understand the sickness (using a logical framing system), and facilitates therapeutic decision making (offering direct therapeutic suggestions).

Results And Conclusion: The paper shows that, compared with all the previous classifications, the 2008 European Glaucoma Society classification is one step ahead (in the way of classifying the group of secondary angle-closure glaucomas), two steps behind (in rejecting two useful categories of congenital glaucoma), and similar in several respects: that it is based on criticizable fundamental and secondary criteria that cannot cover all forms of sickness gathered at a particular crossing; that it uses several equally weighted criteria for one single crossing (division); that it frames one clinical entity in several clinical categories; that it does not reflect reality in some aspects; and that it does not offer direct therapeutic suggestions: after framing a case in a scheme built on the basis of gonioscopic observation, it requires a second stage of pathogenic analysis, so that the ophthalmologist is able to decide the correct treatment only in the third stage.

A new manner of reporting pressure results after glaucoma surgery.

Purpose: To evaluate to what extent contemporary glaucoma abstracts offer complete information and to suggest a new manner of pressure results reporting.

Materials, Methods, And Results: Most of the 36 relevant surgical glaucoma abstracts found in one issue of International Glaucoma Review contain insufficient data-supported statements. Such abstracts cannot offer a clear picture of the study essence if economic, linguistic, or political barriers prevent access to the full text.

[Thinoptix implant--the last border in modern cataract surgery. After 7 months, results of first implants in România].

Purpose: To present the rollable implant and the firsts results after 7 months of usage.

Material And Methods: The implant: ThinOptX Ultra Choice 001 in a rolled state can be implanted through 1.34 mm.

The pathogenic classification of glaucomas.

On the basis of a pathogenic definition, our classification distinguished for each of the first intersections a main--mostly determinant mechanism and a secondary mechanism, mostly modulating the damages: hydrodynamic alteration and tissue resistance alteration--for the second intersection, outflow block and hypersecretion--for the third. Reflecting the state of present knowledge, from the corresponding forms of the disease, only outflow block glaucoma is completely analysed, the exogenous, trabecular, pretrabecular and mixed glaucomas being described. In order to permit the correct framing of all pretrabecular block glaucomas, the posterior push forms (retrovitreal or parietal) were introduced besides the anterior already described forms (pupillary or angular).

[Cancer of the cervix uteri in young people].

The age-group distribution, risk factors, histopathological aspects, diagnosis, treatment and prognosis of 111 diagnosed and/or treated cervical carcinomas in women aged up to 40 years out of 478 cases with the same diagnosis were reviewed. It is considered that the incidence of 23.2% in this series is situated at the extreme of the high frequencies reported in the literature.

[The appropriateness of our therapeutic attitude to expulsive hemorrhage].

Documented data on etiopathogenicity and treatment of expulsive hemorrhage are reviewed and a case reported. Validity of a new therapeutic approach to this lesion was confirmed after treatment consisting mainly of posterior choriodialysis combined with a wide Z-shaped scleral incision.