Simultaneous Quantitation of Venlafaxine and Its Main Metabolite, O-Desmethylvenlafaxine, in Human Saliva by HPLC.

Simultaneous quantitation of venlafaxine and its main metabolite, O-desmethylvenlafaxine, in human saliva by HPLC.

J Sep Sci. 2013 Mar 12;
Dziurkowska E, Wesolowski M

Venlafaxine is used for the treatment of major depression and generalized anxiety disorders. Because its active metabolite, O-desmethylvenlafaxine, has also a similar activity, the purpose of this work was to develop a simple method for simultaneous quantitation of both drugs using HPLC with UV detection. The saliva was chosen as diagnostic material because of its easy accessibility and possibility of sampling by patients, e.g. at home. The sample pretreatment by liquid-liquid extraction allows to separate both compounds from this diagnostic material with a high recovery, varying between 92.65 and 104.78%. The major advantage of the validated method lies in its sensitivity, reproducibility and specificity for routine quantitation of the venlafaxine and O-desmethylvenlafaxine in the human saliva. The low detection and quantification values (2.8-3.1 and 9.4-10.2 ng/mL, respectively) enable to quantify both species excreted with saliva at the nanogram level. The applicability of the method was verified by analysis of the saliva obtained from depressed women treated with venlafaxine. The results suggest that the method could be used for therapeutic drug monitoring in patients undergoing treatment with venlafaxine, especially when metabolic anomalies or low compliance are suspected, or in the case of polypharmacy. HubMed – drug

 

A Light-Driven Anti-Cancer Dual-Therapeutic Cassette Enhances Solid Tumour Regression.

Adv Healthc Mater. 2013 Mar 14;
Kim AR, Shin SW, Cho SW, Lee JY, Kim DI, Um SH

The majority of anticancer therapeutics have failed to control the target cancers. Thus, new rational design concepts are critical. In most of the biological reactions, a cascade pathway is used to activate appropriate responses. In the cascade pathway, a small signal derived from neighboring environments can be amplified and it further triggers overwhelming and specialized responses. It can be applied to achieve powerful therapeutic effects for novel drug design strategies. Inspired by this concept, we design a preferential dual anti-cancer therapeutic cassette composed of (i) DNA/RNA nanostructures as both anticancer containers and target ligands and (ii) a gold nanocrystal as localized heat inducers. We demonstrate that this multi-modular platform is superior to conventional cancer medications in that it had higher drug loading efficiency, tunable drug release, and intrinsic serum stability characteristics. Both doxorubicin chemotherapy and thermal ablation exert a powerful synergistic killing effect that resulted in prostate cancer regression both in vitro and in vivo. We speculate that our novel anti-cancer drug system can be adapted to effectively destroy many different types of solid cancers. HubMed – drug

 

Multifunctional Albumin Nanoparticles As Combination Drug Carriers for Intra-Tumoral Chemotherapy.

Adv Healthc Mater. 2013 Mar 12;
Cui M, Naczynski DJ, Zevon M, Griffith CK, Sheihet L, Poventud-Fuentes I, Chen S, Roth CM, Moghe PV

Current cancer therapies are challenged by weakly soluble drugs and by drug combinations that exhibit non-uniform biodistribution and poor bioavailability. In this study, we have presented a new platform of advanced healthcare materials based on albumin nanoparticles (ANPs) engineered as tumor penetrating, delivery vehicles of combinatorially applied factors to solid tumors. These materials were designed to overcome three sequential key barriers: tissue level transport across solid tumor matrix; uptake kinetics into individual cancer cells; therapeutic resistance to single chemotherapeutic drugs. The ANPs were designed to penetrate deeper into solid tumor matrices using collagenase decoration and evaluated using a three-dimensional multicellular melanoma tumor spheroid model. Collagenase modified ANPs exhibited 1-2 orders of magnitude greater tumor penetration than unmodified ANPs into the spheroid mass after 96 hours, and showed preferential uptake into individual cancer cells for smaller sized ANPs (<100 nm). For enhanced efficacy, collagenase coated ANPs were modified with two therapeutic agents, curcumin and riluzole, with complementary mechanisms of action for combined cell cycle arrest and apoptosis in melanoma. The collagenase coated, drug loaded nanoparticles induced significantly more cell death within 3-D tumor models than the unmodified, dual drug loaded ANP particles and the kinetics of cytotoxicity was further influenced by the ANP size. Thus, multifunctional nanoparticles can be imbued with complementary size and protease activity features that allow them to penetrate solid tumors and deliver combinatorial therapeutic payload with enhanced cancer cytotoxicity but minimal collateral damage to healthy primary cells. HubMed – drug

 

Biodegradable paclitaxel-loaded microparticles prepared from novel block copolymers: influence of polymer composition on drug encapsulation and release.

J Pept Sci. 2013 Mar 12;
Sartori S, Caporale A, Rechichi A, Cufari D, Cristallini C, Barbani N, Giusti P, Ciardelli G

This study covers the preparation of microspheres for the controlled and targeted release of paclitaxel, using novel degradable polymers as carrier materials. Paclitaxel-loaded microspheres were prepared by oil-in-water single-emulsion solvent extraction/evaporation technique by using a series of polyurethanes and a block copolymer; the physicochemical properties of these polymers were modulated by changing nature and composition of their structural units. The obtained microparticles showed a regular morphology and properties (diameter: 1-100?µm; resuspension index: 18.8-100%; encapsulation efficiency: 26.6-97.2%) depending on polymer hydrophilicity and emulsifier used. In vitro release curves showed in all cases almost zero-order kinetics after an initial low burst effect (from 1 to 8.4%), which is required to minimize the drug side effects. This work also proposes a novel strategy to combine a controlled and a targeted release through the functionalization of the polymer matrix with peptide sequences. An RGD-functionalized polyurethane was used to successfully prepare paclitaxel-loaded microparticles. Studies on the preparation of polymer microspheres are reported. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. HubMed – drug