Showing papers by "Dragan Uskoković published in 2009"

Poly(lactide-co-glycolide)-based Micro and Nanoparticles for the Controlled Drug Delivery of Vitamins

Abstract: Controlled drug delivery systems and polymeric carriers have undergone significant development in recent years. Polymers like polylactides (PLA), polyglycolides (PGA), poly(lactide-co-glycolides) (PLGA), are approved by the World Health Organization (WHO) and Food and Drug Administration (FDA) as materials that can be used in medicine and pharmacy. Owing to their biodegradable nature, polymer materials, such as copolymer poly(DL-lactide-co-glycolide), are widely used in various medical applications; controlled release of delivering drugs, carriers in the tissue engineering, fixation of bone fractures, chirurgical strings, etc. Polymeric particles are used for the controlled delivery of several types of medicaments, including anticancer agents, antihypertensive agents, immunomodulatory drugs, hormones, vitamins and macromolecules, such as nucleic acid, proteins, peptides, antibodies, etc. Preparation of poly(lactide-co-glycolide) submicron spheres poses serious challenges. The present review attempts to address some important issues related to micro/nanoparticle-based delivery systems comprising poly(lactide-co-glycolide), with a special reference to PLGA for the controlled delivery of vitamins. A range of topics is discussed, including formulation aspects of micro- and nanoparticles, the effects of particle size and size distribution, most commonly used incorporation techniques, surface modification with stabilizers, surface functionalization, and factors affecting degradation and drug release rate. A post-print version of the article: Uskokovic, Dragan, and Magdalena Stevanovic. 2009. “Poly(lactide-Co-Glycolide)-Based Micro and Nanoparticles for the Controlled Drug Delivery of Vitamins.” Current Nanoscience 5 (1) (February 1): 1–14. doi:10.2174/157341309787314566.

Hydrothermal Synthesis of Nanosized Pure and Cobalt-Exchanged Hydroxyapatite

Abstract: Pure and cobalt-exchanged hydroxyapatite (HAp and CoHAp) powders were synthesized by hydrothermal method. X-ray diffraction (XRD), Raman spectroscopy, particle size analysis, inductively coupled plasma (ICP) emission spectroscopy, and scanning electron microscopy (SEM) were used to study the microstructural and unit cell parameters, average particle size, particle size distribution, chemical composition, and morphology of the synthesized powders. XRD and Raman spectroscopy confirmed that the samples were free from impurities and other phases of calcium phosphates. It has been found that the increase in the cobalt amount in the crystal structure of HAp reduces unit cell parameters, as well as average crystallite size (from XRD measurements). All of the powders were nano-sized with narrow particle distribution (from particle size analyses). SEM investigations indicated that nano-sized particles were organized in soft micro-sized agglomerates, whose sizes increased with the increase in the content of Co in HAp crystal structure.

An innovative, quick and convenient labeling method for the investigation of pharmacological behavior and the metabolism of poly(DL-lactide-co-glycolide) nanospheres

Abstract: Nanoparticles of poly(DL-lactide-co-glycolide) (PLGA) in the size range 90-150 nm were produced using the physicochemical method with solvent/non-solvent systems. The encapsulation of the ascorbic acid in the polymer matrix was performed by homogenization of the water and organic phases. In vitro degradation and release tests of PLGA nanoparticles with and without encapsulated ascorbic acid were studied for more than 60 days in PBS and it has been determined that PLGA completely degrades within this period, fully releasing all encapsulated ascorbic acid. The cytotoxicity of PLGA and PLGA/ascorbic acid 85/15% nanoparticles was examined with human hepatoma cell lines (HepG2 ECACC), in vitro. The obtained results indicate that neither PLGA nanospheres nor PLGA/ascorbic acid 85/15% nanoparticles significantly affected the viability of the HepG2 cells. The investigation of the distribution and pharmacokinetics of PLGA is crucial for the effective prediction of host responses to PLGA in particular applications. Thus we present a method of labeling PLGA nanospheres and PLGA/ascorbic acid 85/15 wt% nanoparticles by (99m)Tc which binds outside, leaving the cage intact. This enables a quick and convenient investigation of the pharmacological behavior and metabolism of PLGA. The biodistribution of (99m)Tc-labeled PLGA particles with and without encapsulated ascorbic acid after different periods of time of their installation into rats was examined. PLGA nanospheres with encapsulated ascorbic acid exhibit prolonged blood circulation accompanied by time-dependent reduction in the lungs, liver and spleen, and addition in the kidney, stomach and intestine. The samples were characterized by x-ray diffraction, scanning electron microscopy, stereological analysis, transmission electron microscopy, ultraviolet spectroscopy and instant thin layer chromatography.

Densification, Microstructure, and Electrical Properties of BaTiO3 (BT) Ceramics Prepared from Ultrasonically De-Agglomerated BT Powders

Abstract: In this study, a correlation between densification, microstructure, and electrical properties of BaTiO3 (BT) ceramics prepared from ultrasonically de-agglomerated BT powders has been analyzed. BT powders with the same crystal structure (tetragonal) and stoichiometry, but with different average particle size, were used to prepare sintered ceramics. Densification and electrical properties of the sintered BT ceramics were correlated to the average particle size of the powders. It was found that a decrease in average particle size improved the densification process as well as the ceramics' microstructure. The impedance measurements were done up to 320°C in order to separate grain (bulk) and grain boundary contributions. Bulk resistance was more or less the same, independent on the average particle size of the powder. On the contrary, grain boundary resistance increased with decreasing average particle size of the powder.

The master sintering curves for BaTi0.975Sn0.025O3/BaTi0.85Sn0.15O3 functionally graded materials

Abstract: The most important aim in the design and processing of functionally graded materials (FGMs) is to produce devices free from any deformation. Smart choices of different combination of graded layers, as well as the heating rate during sintering, are important for the fabrication of high-quality FGMs. In this study, BaTi 0.975 Sn 0.025 O 3 /BaTi 0.85 Sn 0.15 O 3 (noted as BTS2.5 and BTS15, respectively) FGM was used as a model system for the construction of master sintering curves (MSCs) and estimation of the effective activation energies of sintering for different BTS graded layers. The MSCs were constructed, for BTS2.5 and BTS15 graded layers in FGMs, using shrinkage data obtained by a heating microscope during sintering at four constant heating rates, 2, 5, 10 and 20 °/min. The effective activation energies were determined using the concept of MSC; values of 359.5 and 340.5 kJ/mol were obtained for graded layers BTS2.5 and BTS15, respectively. A small difference of the effective activation energies of chosen powders made it possible for us to prepare high-quality FGMs, without delamination, distortion or other forms of defects.

Influence of different degradation medium on release of ascorbic acid from poly(D,L-lactide-co-glycolide) nano- and microspheres

Abstract: The major goals of the present study were to examine the effects of the type of release medium on the resulting drug release kinetics and to get further insight into the underlying drug release mechanisms. Spherical micro and nanoparticles were prepared by a physicochemical solvent/nonsolvent method with polyvinyl pyrrolidone as a surfactant and characterized with ultraviolet spectroscopy and scanning electron microscopy before and upon exposure to various release media.

Controllable Synthesis of Horseradish Peroxidase Loaded Poly(D,L-lactide) Nanospheres

Abstract: In this work, horseradish peroxidase (HRP), a model protein, was encapsulated by the precipitation method with additional step of homogenization, using polymer poly(D,L-lactide) (PDLLA). The purpose of this study was to expand the application of a modified precipitation method to HRPloaded PDLLA spheres and to find optimal conditions for preparing HRP-loaded PDLLA spheres with the best properties, with size under 1000 nm. Influence of process variables on the size and morphology of the particles has been studied. Size of the spheres depends on homogenization speed, co-solvent selection, chloroform to water ratio and PVA concentration. Particle size was ranging between 460 nm and 1130 nm, according to the preparation conditions. The optimized conditions yielded nanospheres with 46% encapsulation efficiency and average diameter of 530 nm. A particle size under 1000 nm enables intravascular injection and is also desirable for intramuscular and subcutaneous administration, minimizing possible irritant reactions. It was found that modified precipitation method was widely applicable to HRP-loaded PDLLA spheres, by choosing optimal preparation conditions.