1,721,233 research outputs found
Microfluidic Mixing: A General Method for Encapsulating Hydrophilic / Hydrophobic Low Molecular Weight Drugs in PLGA Nanoparticles
Purpose: microfluidics, the technology of manipulating and controlling fluids on the nanoliter scale in milliseconds, has recently emerged as promising and easy scalable method for nanoparticles (NPs) manufacturing. The aim of the work was to clarify and set up microfluidics assisted nanoprecipitation method process parameters which specifically influence poly(lactide-co-glycolide) NPs features. The evaluation of the effect of critical parameters in the microfluidic process has taken care: i) NPs physical characteristics and ii) the amount of hydrophilic/hydrophobic drug loaded.
Methods: uncapped poly(lactide-co-glycolide) (PLGA; DLG 7525, 25 KDa), was the selected polymer and N-Acetylcysteine and Dexamethasone were respectively used as hydrophilic and hydrophobic model drugs because of their encapsulation problem widely reported in literature. Within the range of microfluidic mixing devices, a chaotic advection micromixer, a staggered herringbone micromixer (SHM) was selected (Precision NanoSystem, Vancouver, Canada). PLGA was dissolved in acetonitrile as organic solvent and aqueous Tris buffer (10 mM, pH 6.8) was chosen as non-solvent. A Full Factorial Design (FFD; 16, 2*4) was employed to optimize the process parameters of microfluidics assisted nanoprecipitation method: flow rate ratio (FRR), polymer concentration and polymer to drug ratio were selected as factors. Particle size (dynamic light scattering method) and encapsulation efficiency (HPLC analyses) were the outcomes considered. Moreover, the NPs morphology was revealed through transmission electron microscopy (TEM).
Results: models obtained by the statistical analysis carried out on runs of FFD allowed to identify the effect of each factor on the specific outcome. Significant effects on NPs physical proprieties were highlighted as a function of flow rate ratio (FRR) and total flow rate (TFR). In particular increasing the TFR (from 5 to 15 mL/min) and FRR (from 1:1 to 5:1 v/v, buffer: acetonitrile) NPs mean diameter decreased from 382.3 ±18.9 to 126.4± 10.2 and from 889.3 ±21.6 to 126.4± 10.2, respectively. The effect of process parameter were also verified by TEM analysis; TEM images revealed a spherical regular shape and low particle size for NPs obtained at higher FRR while for a 1:1 FRR photomicrographs showed NP with irregular morphology and high particle size confirming data recorded by dynamic light scattering. Furthermore, the effect of varying the PLGA concentration was evaluated, in particular reducing polymer concentration particle size decreased till reach a limit size of 50nm which depends on the physical-chemical characteristics of the polymer (molecular weight and structure). Finally, hopeful results were obtained in terms of drug encapsulation into PLGA NPs in comparison with traditional method: using a TFR of 15 mL/min and a 5:1 FRR very high encapsulation efficacies were obtained, 68% for N-Acetylcysteine and 72% for Dexamethasone.
Conclusions: this preliminary work demonstrates that microfluidic-assisted nanoprecipitation using a SHM micromixer can successfully be exploited to manufacture PLGA NPs with desired size characteristics controlling parameters such as TFR, FRR and polymer concentration. Set-up microfluidic technique has also emerged as powerful and more effective method for improving loading of small hydrophilic and hydrophobic drugs in PLGA NPs
Effects of ionizing radiation sterilization on microparticulate drug delivery systems based on poly-alfa-hydroxyacids: an overview.
Ionizing radiation treatment is particularly advantageous as a sterilization technique for polymeric drug delivery systems. In recent years
several authors have investigated this topic with interesting and sometimes controversial results. This overview was aimed at gathering and critically
discussing the studies performed on the effect of ionizing radiation sterilization on microparticulate drug delivery systems made of poly-α-
hydroxyacids. The results reported in the literature showed that ionizing radiation always led to a decrease in poly-α-hydroxyacids molecular
weight. This effect was strictly related to irradiation dose, irradiation conditions, and depended on the starting polymer molecular weight. The
presence of a drug and/or an additive inside the polymeric micromatrix could affect polymer behavior upon irradiation and consequently drug
release behavior. Electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) proved to be useful techniques to
elucidate the radiolytic mechanisms and the drug /polymer interaction upon irradiation
An injectable in situ forming composite gel to guide bone regeneration: Design and development of technology platform
Effect of porogen on the physico-chemical properties and degradation performance of PLGA scaffolds
The aim of the study was to examine the relationship between the structural features of PLGA 3-D
scaffolds and their degradation performances. PLGA 3-D scaffolds were fabricated by solvent casting and
particulate leaching using salt and sucrose particles as porogen and they were characterized in terms of
structure, physico-chemical and mechanical properties. The in vitro degradation study was performed at
37 C in PBS for 28 days and it included the determination of Mw, Mn, PI, water uptake, mass loss and pH
changes of the degradation buffer. It was found that the preparation method scaffolds, in particular the
choice of the porogen type and was responsible for the three-dimensional structure (pore size, porosity,
apparent density and, mechanical properties) of the scaffold and for physico-chemical PLGA polymer
modifications (polymer degradation reactions, polymer chain rearrangement, Tg changes). Scaffolds with
high porosity (83.8e89.4%) and an interconnected network were obtained
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