1,720,990 research outputs found
Controlled Release of Insulin Granules from PLGA Microparticles for Glucose Modulation in Diabetes
No full textHelicobacter Pylori ATCC 43629 outer membrane vesicles (OMVs): a vehicle for extracellular DNA (eDNA) transport.
No full text
Needle‐Free Jet Injectors for Dermal and Transdermal Delivery of Actives
No full textNeedle‐free jet injectors are medical devices used for the delivery of liquid medications across the skin as a high‐speed stream of fluid, without the use of a needle. The absence of a needle abolishes the risk of needle‐stick injuries, frequent among healthcare providers, and increases the compliance to injections in needle‐phobic patients. Through the modulation of several parameters of the jet injectors, the liquid medication can be delivered to different sites within or below the skin, thus allowing the use of such devices for both local and systemic therapies in a multitude of disorders. In the present chapter, after a brief historical overview, the functioning principles and the rationale behind the use of needle‐free jet injectors are presented. Moreover, preclinical and clinical studies where jet injectors have been employed for the systemic or local delivery of therapeutics are reviewed. Finally, in the last section, the potential of such devices for the administration of nano‐ and micro‐particulate drug delivery systems is discussed
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
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
Physicochemical characterization of non ionic surfactant vesicles forming innovative supramolecular nanocarriers
No full text- …
