Walter E. Rudzinski

Biodegradable polymeric nanoparticles as drug delivery devices

This review presents the most outstanding contributions in the field of biodegradable polymeric nanoparticles used as drug delivery systems. Methods of preparation, drug loading and drug release are covered. The most important findings on surface modification methods as well as surface characterization are covered from 1990 through mid-2000.

Stimulus-Responsive “Smart” Hydrogels as Novel Drug Delivery Systems

ABSTRACT Recently, there has been a great deal of research activity in the development of stimulus-responsive polymeric hydrogels. These hydrogels are responsive to external or internal stimuli and the response can be observed through abrupt changes in the physical nature of the network. This property can be favorable in many drug delivery applications. The external stimuli can be temperature, pH, ionic strength, ultrasonic sound, electric current, etc. A majority of the literature related to the development of stimulus-responsive drug delivery systems deals with temperature-sensitive poly(N-isopropyl acrylamide)(pNIPAAm) and its various derivatives. However, acrylic-based pH-sensitive systems with weakly acidic/basic functional groups have also been widely studied. Quite recently, glucose-sensitive hydrogels that are responsive to glucose concentration have been developed to monitor the release of insulin. The present article provides a brief introduction and recent developments in the area of stimulus-responsive hydrogels, particularly those that respond to temperature and pH, and their applications in drug delivery. *CEPS Communications #4.

Chitosan as a carrier for targeted delivery of small interfering RNA

The recent discovery of RNA interference (RNAi) technology for gene therapy has triggered extensive research efforts for developing small interfering RNA (siRNA) loaded nanocomplexes of chitosan and its derivatives for silencing genes. Due to its large molecular weight (∼13 kDa) and polyanionic nature (∼40 negative phosphate groups), naked siRNA does not freely cross the cell membrane. Therefore, its efficient intracellular delivery requires suitable carriers to overcome the intrinsic, poor intracellular uptake and limited blood stability. Among viral and non-viral delivery vectors, the use of non-viral vectors such as chitosan or its derivatives is attractive, since these polymers are biodegradable, biocompatible, with low toxicity and high cationic potential. Even though much of the technology-base has been well established for targeted delivery of plasmid DNA using chitosan and its derivatives, only recently, has the technology been applied to the targeted delivery of siRNA. This review will explore the factors that are most important in enhancing transfection efficiency and cell specificity in vitro and in vivo including degree of deacetylation, molecular weight and chemical modification of chitosan, pH, and the charge ratio of chitosan to siRNA.

In-vitro release kinetics of cefadroxil-loaded sodium alginate interpenetrating network beads.

This paper reports the development of new interpenetrating polymeric networks of sodium alginate with gelatin or egg albumin cross-linked with a common cross-linking agent, glutaraldehyde, for the in-vitro release of cefadroxil. The beads formed were characterized by Fourier transform infra-red spectroscopy, scanning electron microscopy and differential scanning calorimetry. Swelling/drying experiments were performed to compute the diffusion coefficients and the molecular mass between cross-links of the beads. The release results were evaluated using an empirical equation to understand the transport mechanism. The extent of cross-linking was studied in terms of the size and release characteristics of the beads. The experimental and derived quantities have been used to study their dependencies on the nature of the polymeric beads, transport mechanism, encapsulation efficiency and drug diffusion, as well as the cross-linking abilities of the polymers.

Hydrogels as controlled release devices in agriculture

Recently, there has been a great deal of research activity in the development of hydrogels as controlled release devices. The present review provides a brief introduction to various methods of synthesis, properties, types of hydrogels, and cross-linking agents which have been used for the preparation of hydrogels exhibiting suitable properties for agricultural applications.

Fluorescence Assay Based on Aptamer-Quantum Dot Binding to Bacillus thuringiensis Spores

A novel assay was developed for the detection of Bacillus thuringiensis (BT) spores. The assay is based on the fluorescence observed after binding an aptamer-quantum dot conjugate to BT spores. The in vitro selection and amplification technique called SELEX (Systematic Evolution of Ligands by EXponential enrichment) was used in order to identify the DNA aptamer sequence specific for BT. The 60 base aptamer was then coupled to fluorescent zinc sulfide-capped, cadmium selenide quantum dots (QD). The assay is semi-quantitative, specific and can detect BT at concentrations of about 1,000 colony forming units/ml.

MICROSPHERES AS FLOATING DRUG-DELIVERY SYSTEMS TO INCREASE GASTRIC RETENTION OF DRUGS

Gastric emptying is a complex process, which is highly variable and makes in vivo performance of the drug-delivery systems uncertain. In order to avoid this variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 h. The floating or hydrodynamically controlled drug-delivery systems are useful in such applications. The present review addresses briefly the physiology of the gastric emptying process with respect to floating drug-delivery systems. In recent years, the multiparticulate drug-delivery systems are used in the oral delivery of drugs. One of the approaches toward this goal is to develop the floating microspheres so as to increase the gastric retention time. Such systems have more advantages over the single-unit dosage forms. The development of floating microspheres involves different solvent evaporation techniques to create the hollow inner core. The present review addresses the preparation and characterization of the floating microspheres for the peroral route of administration of the drug.

Cyclodextrin-based siRNA delivery nanocarriers: a state-of-the-art review

Introduction: The discovery of synthetic small interfering RNA (siRNA) has led to a surge of interest in harnessing RNA interference (RNAi) technology for biomedical applications and drug development. Even though siRNA can be a powerful therapeutic drug, its delivery remains a major challenge, due to the difficulty in its cellular uptake. Naked siRNA has a biological half-life of less than an hour in human plasma. To increase the lifetime and improve its therapeutic efficacy, non-viral vectors have been developed. As a natural evolution, cyclodextrins (CDs), which are natural cyclic oligosaccharides, have recently been applied as delivery vehicles for siRNA, and this in turn, has led to a surge of interest in this area. Areas covered: This review discusses the recent advances made in the design of delivery strategies for siRNA, focusing on CD-based delivery vectors, because these have demonstrated clinical success. The methods of preparation of CD-based vectors, their characterization, transfection efficiencies, cellular toxicity, preclinical and clinical trials are also addressed, as well as future therapeutic applications. Expert opinion: siRNA-mediated RNAi therapeutics is beginning to transform healthcare, particularly, for the treatment of solid tumors. For example, CALAA01, a targeted, self-assembling nanoparticle system based on CD complexed with siRNA has been effective in phase I clinical trials. Although siRNA therapeutics suffers from problems related to off-target effects and non-specific gene silencing, these problems can be overcome by reducing the nanoparticle size, improving the targeting efficiency and by modifying the primary sequence of the siRNA.

Sampling and Analysis of Isocyanates in Spray-Painting Operations

Several methods were used for the sampling and analysis of airborne 1,6-hexamethylene diisocyanate (HDI) and polyisocyanates during spray-painting operations. National Institute for Occupational Safety and Health (NIOSH)Method 5521 uses an impinger filled with 1-(2methoxyphenyl)piperazine in toluene for collection and derivatization, HPLC separation, and simultaneous UV and EC detection. This method was compared directly to Occupational Safety and Health Administration (OSHA) Method 42, which is based on sample collection on a fiber filter coated with 1-(2-pyridyl)piperazine, HPLC separation, then UV detection. NIOSH Method 5521, modified so that polyisocyanate concentrations were determined based on polyisocyanate standards, also was compared with NIOSH Method 0500, which is a gravimetric assay for total particulates. The results for HDI monomer demonstrate that NIOSH Method 5521 appears to give higher results than those obtained using OSHA Method 42, especially when the total particulate concentration i...

Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles.

Small interfering RNA (siRNA) molecules specifically target messenger RNA species, decreasing intracellular protein levels. β-Catenin protein concentrations are increased in 70-80% of colon tumors, promoting tumor progression. Chitosan exhibits low levels of toxicity and can be transported across mucosal membranes; therefore, our objective was to develop chitosan and poly(ethylene glycol)-grafted (PEGylated) chitosan nanoparticles, 100-150nm in diameter, encapsulating anti-β-catenin siRNA for transfection into colon cancer cells. Encapsulation efficiencies up to 97% were observed. Confocal microscopy visualized the entry of fluorescently-tagged siRNA into cells. Western blot analysis showed that both chitosan and PEGylated chitosan nanoparticles containing anti-β-catenin siRNA decreased β-catenin protein levels in cultured colon cancer cells. These results indicate that nanoparticles made with chitosan and PEGylated chitosan can successfully enter colon cancer cells and decrease the level of a protein that promotes tumor progression. These or similar nanoparticles may prove beneficial for the treatment of colon cancer in humans.