1,720,975 research outputs found
An implantable device for localized drug delivery, uses thereof and a manufacturing method thereof
No full textQuantitative micro-Raman analysis of micro-particles in drug delivery
No full textPolymeric micro and nanoconstructs are emerging as promising delivery systems for therapeutics and contrast agents in microcirculation. Excellent assets associated with polymeric particulates of tunable shape, size, mechanical and chemical properties may improve the efficiency of delivery and represent the basis of personalized medicine and treatment. Nevertheless, lack of effective techniques of analysis may limit their use in biomedicine and bioengineering. In this paper, we demonstrated Raman Spectroscopy for quantitative characterization of poly lactic-co-glycolic acid (PLGA) micro-plate drug delivery systems. To do so, we (i) acquired bi-dimensional Raman maps of PLGA micro-plates loaded with curcumin at various times of release over multiple particles. We (ii) realized an exploratory analysis of data using the principal component analysis (PCA) technique to find hidden patterns in the data and reduce the dimensionality of the system. Then, we (iii) used an innovative univariate method of analysis of the reduced system to derive quantitative drug release profiles. High performance liquid chromatography (HPLC), the consolidated method of analysis of macro-sized systems, was used for comparison. We found that our system is as efficient as HPLC but, differently from HPLC, it enables quantitative analysis of systems at the single particle level
Boosting the therapeutic efficacy of discoidal nanoconstructs against glioblastoma with rationally designed PEG-Docetaxel conjugates
Full text linkMaximizing loading while modulating the release of therapeutic molecules from nanoparticles and implantable drug delivery systems is the key to successfully address deadly diseases like brain cancer. Here, four different conjugates of the potent chemotherapeutic molecule docetaxel (DTXL) were realized to optimize the pharmacological properties of 1,000 × 400 nm Discoidal Polymeric Nanoconstructs (DPNs). DTXL was covalently linked to poly-(ethylene) glycol (PEG) chains of different molecular weights, namely 350, 550 and 1,000 Da, and oleic acid (OA). After extensive physico-chemical and pharmacological characterizations, the conjugate PEG550-DTXL showed an optimal compromise between loading and sustained release out of DPNs, as opposed to the insufficient loading of PEG1000-DTXL and PEG350-DTXL and the excessively slow release of OA-DTXL. Not surprisingly, viability tests conducted on U87-MG cells showed a delay in cytotoxic activity for the DTXL conjugates compared to free DTXL within the first 48 h. However, PEG550–DTXL returned an IC50 value of ∼ 10 nM at 72 h, which is comparable to free DTXL. In mice bearing orthotopically implanted U87-MG cells, the intravenous administration of PEG550-DTXL loaded DPNs doubled the overall animal survival (52.5 days) as compared to temozolomide (27 days) and the untreated controls (32 days). Collectively, these results continue to demonstrate that the therapeutic efficacy of nanoparticles can be boosted by rationally designing drug conjugates-particle complexes for optimal loading and release profiles
Controlled Release of Insulin Granules from PLGA Microparticles for Glucose Modulation in Diabetes
No full textμMESH-Enabled Sustained Delivery of Molecular and Nanoformulated Drugs for Glioblastoma Treatment
No full textModest tissue penetrance, nonuniform distribution, andsuboptimalrelease of drugs limit the potential of intracranial therapies againstglioblastoma. Here, a conformable polymeric implant, & mu;MESH,is realized by intercalating a micronetwork of 3 x 5 & mu;mpoly(lactic-co-glycolic acid) (PLGA) edges over arraysof 20 x 20 & mu;m polyvinyl alcohol (PVA) pillars for the sustaineddelivery of potent chemotherapeutic molecules, docetaxel (DTXL) andpaclitaxel (PTXL). Four different & mu;MESH configurations wereengineered by encapsulating DTXL or PTXL within the PLGA micronetworkand nanoformulated DTXL (nanoDTXL) or PTXL (nanoPTXL) within the PVAmicrolayer. All four & mu;MESH configurations provided sustaineddrug release for at least 150 days. However, while a burst releaseof up to 80% of nanoPTXL/nanoDTXL was documented within the first4 days, molecular DTXL and PTXL were released more slowly from & mu;MESH.Upon incubation with U87-MG cell spheroids, DTXL-& mu;MESH was associatedwith the lowest lethal drug dose, followed by nanoDTXL-& mu;MESH,PTXL-& mu;MESH, and nanoPTXL-& mu;MESH. In orthotopic models ofglioblastoma, & mu;MESH was peritumorally deposited at 15 days post-cellinoculation and tumor proliferation was monitored via bioluminescenceimaging. The overall animal survival increased from & SIM;30 daysof the untreated controls to 75 days for nanoPTXL-& mu;MESH and90 days for PTXL-& mu;MESH. For the DTXL groups, the overall survivalcould not be defined as 80% and 60% of the animals treated with DTXL-& mu;MESHand nanoDTXL-& mu;MESH were still alive at 90 days, respectively.These results suggest that the sustained delivery of potent drugsproperly encapsulated in conformable polymeric implants could haltthe proliferation of aggressive brain tumors
Engineering shape-defined PLGA microPlates for the sustained release of anti-inflammatory molecules
No full textOver the years, nanoparticles, microparticles, implants of poly(D,L-lactide-co-glycolide) (PLGA) have been demonstrated for diverse biomedical applications. Yet, initial burst release and optimal modulation of the release profiles limit their clinical use. Here, shape-defined PLGA microPlates (μPLs) were realized for the sustained release of two anti-inflammatory molecules, the natural polyphenol curcumin (CURC) and the corticosteroid dexamethasone (DEX). Under the electron microscope, μPLs appeared as square prisms with an edge length of 20 μm. The top-down fabrication process allowed the authors to vary, readily and systematically, the μPL height from 5 to 10 μm and the PLGA mass from 1 to 5, 10 and 20 mg. ‘Taller’ particles realized with higher PLGA concentrations encapsulated more drug reaching on average values of about 150 pg/μPL, for both CURC and DEX. The μPL height and PLGA concentration had major effects on drug release, too. Under sink conditions, DEX release from tall μPLs at 1 h reduced from 50% to 10% and 2% for the 5, 10 and 20 mg PLGA configurations, respectively. Also, DEX was released more slowly from taller as compared to short μPLs. The opposite trend was observed for CURC, possibly for its lower hydrophobicity and molecular weight as compared to DEX. This was also confirmed by quantifying the free energy of translocation for the two drugs via molecular dynamics simulations. Finally, the anti-inflammatory activity of μPLs was tested in vitro on LPS-stimulated rat monocytes and in vivo on a murine model of UVB-induced skin burns. Both in vitro and in vivo, the expression of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) was significantly reduced by the application of μPLs as compared to the free compounds. In vivo, one single topical deposition of CURC-μPLs outperformed multiple, free CURC applications. This work demonstrates that geometry and polymer density can be effectively used to modulate the pharmacological performance of microparticles and mitigate the initial burst release
Enhancing islet transplantation using a biocompatible collagen-PDMS bioscaffold enriched with dexamethasone-microplates
No full textIslet transplantation is a promising approach to enable type 1 diabetic patients to attain glycemic control independent of insulin injections. However, up to 60% of islets are lost immediately following transplantation. To improve this outcome, islets can be transplanted within bioscaffolds, however, synthetic bioscaffolds induce an intense inflammatory reaction which can have detrimental effects on islet function and survival. In the present study, we first improved the biocompatibility of polydimethylsiloxane (PDMS) bioscaffolds by coating them with collagen. To reduce the inflammatory response to PDMS bioscaffolds, we then enriched the bioscaffolds with dexamethasone-loaded microplates (DEX-μScaffolds). These DEX-microplates have the ability to release DEX in a sustained manner over 7 weeks within a therapeutic range that does not affect the glucose responsiveness of the islets but which minimizes inflammation in the surrounding microenvironment. The bioscaffold showed excellent mechanical properties that enabled it to resist pore collapse thereby helping to facilitate islet seeding and its handling for implantation, and subsequent engraftment, within the epididymal fat pad (EFP). Following the transplantation of islets into the EFP of diabetic mice using DEX-μScaffolds there was a return in basal blood glucose to normal values by day 4, with normoglycemia maintained for 30 d. Furthermore, these animals demonstrated a normal dynamic response to glucose challenges with histological evidence showing reduced pro-inflammatory cytokines and fibrotic tissue surrounding DEX-μScaffolds at the transplantation site. In contrast, diabetic animals transplanted with either islets alone or islets in bioscaffolds without DEX microplates were not able to regain glycemic control during basal conditions with overall poor islet function. Taken together, our data show that coating PDMS bioscaffolds with collagen, and enriching them with DEX-microplates, significantly prolongs and enhances islet function and survival
Ameliorating Amyloid-β Fibrils Triggered Inflammation via Curcumin-Loaded Polymeric Nanoconstructs
No full textInflammation is a common hallmark in several diseases, including atherosclerosis, cancer, obesity, and neurodegeneration. In Alzheimer’s disease (AD), growing evidence directly correlates neuronal damage with inflammation of myeloid brain cells, such as microglia. Here, polymeric nanoparticles were engineered and characterized for the delivery of anti-inflammatory molecules to macrophages stimulated via direct incubation with amyloid-β fibers. 200 nm spherical polymeric nanoconstructs (SPNs) and 1,000 nm discoidal polymeric nanoconstructs (DPNs) were synthesized using poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and lipid chains as building blocks. First, the internalization propensity in macrophages of both nanoparticles was assessed via cytofluorimetric and confocal microscopy analyses, demonstrating that SPNs are by far more rapidly taken up as compared to DPNs (99.6 ± 0.11 vs 14.4 ± 0.06%, within 24 h). Then, Curcumin-loaded SPNs (Curc-SPNs) were realized by encapsulating Curcumin, a natural anti-inflammatory molecule, within the PLGA core of SPNs. Finally, Curc-SPNs were shown to diminish up to 6.5-fold the production of pro-inflammatory cytokines—IL-1β; IL-6, and TNF-α—in macrophages stimulated via amyloid-β fibers. Although more sophisticated in vitro models and systematic analyses on the blood–brain barrier permeability are critically needed, these findings hold potential in the development of nanoparticles for modulating inflammation in AD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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