Membrane-encased polymer millirods for sustained release of 5-fluorouracil

Abstract: This article describes the design and development of a novel membrane-encased polymer millirod for the sustained release of an anticancer drug, 5-fluorouracil (5-FU). The millirod consists of two functional compartments: (1) an inner 5-FU-loaded monolithic millirod as the drug depot, and (2) an outer NaCl-impregnated polymer membrane to control the release rate of 5-FU. The inner millirod is fabricated by a compression-heat molding procedure to permit the entrapment of 5-FU particles in the poly(D,Llactide-co-glycolide) (PLGA) matrix. The drug loading density is controlled at 30 w/w% to achieve a burst release of 5-FU (>90% of the drug are released within 48 h) from the monolithic millirod. The NaCl-impregnated PLGA membrane is generated by solvent casting and is then wrapped over the monolithic millirod to produce the membraneencased millirod. Scanning electron microscopy shows that dissolution of NaCl particles produces a semipermeable polymer membrane to provide a sustained release of 5-FU. The membrane thickness and the density of NaCl particles inside the membrane are useful parameters to control the release kinetics of 5-FU. Under the experimental conditions in this study, sustained release of 5-FU [rates between 0.1 and 0.4 mg/(day и cm of millirod)] is achieved for 2 to 5 weeks in phosphate-buffered saline (pH 7.4) at 37°C. Results from this study demonstrate that membrane-encased polymer millirods provide controllable sustained release kinetics for applications in intratumoral drug delivery

Big impact of nanoparticles: analysis of the most cited nanopharmaceuticals and nanonutraceuticals research

Nanopharmaceuticals and nanonutraceuticals research has been lately receiving a lot of scientific attention. We aimed to identify the top 100 most cited original articles of the scientific area, analyze their research themes, major contributors regarding authors, institutions, countries and journals. The bibliometric data was extracted from the Web of Science electronic database. Data was further processed by a bibliometric software, VOSviewer, to generate bubble maps to visualize the results. Inter-institutional and international collaboration networks were constructed to further understand the cooperation between different study centers. Results revealed that over 60% of the articles were published in the 2000s. As of November 2019, the articles were cited 5763665 times, with 20.1261.8 citations per year. The majority of the most prolific institutions were based in the United States. Besides the United States, China, South Korea, Canada and Germany contributed heavily to the 100 articles. Some popular themes included drug delivery, tumor, toxicity / biocompatibility and biodistribution. Regarding composition materials, gold, silver and polymeric nanoparticles were the most commonly used.Atanas G. Atanasov acknowledges the support by the Polish KNOW (Leading National Research Centre) Scientific Consortium “Healthy Animal-Safe Food,” decision of Ministry of Science and Higher Education No. 05-1/KNOW2/2015. The support of the research project: Nutraceutica come supporto nutrizionale nel paziente oncologico, CUP: B83D18000140007, Italy is acknowledged.info:eu-repo/semantics/publishedVersio

Magnetic resonance imaging (MRI) contrast agents for tumor diagnosis

10.1260/2040-2295.4.1.23Journal of Healthcare Engineering4123-4

Polymeric Micelles in Anticancer Therapy: Targeting, Imaging and Triggered Release

Micelles are colloidal particles with a size around 5–100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use in patients with breast cancer. Micelle-based drug delivery, however, can be improved in different ways. Targeting ligands can be attached to the micelles which specifically recognize and bind to receptors overexpressed in tumor cells, and chelation or incorporation of imaging moieties enables tracking micelles in vivo for biodistribution studies. Moreover, pH-, thermo-, ultrasound-, or light-sensitive block copolymers allow for controlled micelle dissociation and triggered drug release. The combination of these approaches will further improve specificity and efficacy of micelle-based drug delivery and brings the development of a ‘magic bullet’ a major step forward

Preparation and Characterization of MUC-30-Loaded Polymeric Micelles against MCF-7 Cell Lines Using Molecular Docking Methods and In Vitro Study

MUC-30 is a hydrophobic compound which is active against the MCF-7 cancer cell line. In this study, MUC-30 was loaded in polymeric micelles to improve the water solubility and release rate. For prolonged MUC-30 release, MUC-30 was encapsulated in polymeric micelles using PEG-b-PLA and PEG-b-PCL as materials. Micelles prepared with 1 : 9 w per w ratios by film hydration achieved the highest entrapment efficiency (EE%). The EE% of MUC-30-loaded PEG-b-PCL micelles was approximately 30% greater than that of PEG-b-PLA micelles, due to the different H-bond formations between MUC-30 and the polymer membrane (PCL, 4; PLA, 3). The cytotoxic activity of MUC-30 against EGFR theoretically presented 399.31 nM (IC50 = 282.26 ng/mL) by molecular docking. In vitro cytotoxic activity of MUC-30 was confirmed by MTT assay. MUC-30 (IC50 = 11 ± 0.39 ng/mL) showed three-fold higher activity over MUC-30-loaded PEG-b-PLA micelles (IC50 = 37 ± 1.18 ng/mL) and two-fold higher over PEG-b-PCL micelles (IC50 = 75 ± 3.97 ng/mL). This was due to the higher release rate of MUC-30 from PEG-b-PLA micelles compared to PEG-b-PCL micelles. Therefore, MUC-30-loaded PEG-b-PLA micelles could be a promising candidate for breast cancer chemotherapy

Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

Abstract Diblock copolymers of poly(q-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5 -24.7 kDa) in the copolymer composition. Hemolytic studies showed that free DOX caused 11% hemolysis at 200 Ag ml À 1 , while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 jC demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells