Design of novel polyurethane-based ionene nanocarriers for cancer therapy: Synthesis, in-vitro, and in-vivo studies.

New strategies for constructing versatile nanocarriers are needed for cancer therapy to overcome the multiple challenges of targeted delivery. This work explores the advantages of polyurethane with main-chain quaternary ammonium salt moieties (ionene) as a novel carrier for targeted drug delivery. We have developed a novel cationic soybean oil-based polyurethane ionene nanocarrier (CPUI) that can act as an effective anticancer agent and efficiently deliver the anticancer drug 5-fluorouracil (5FU).

Interactions in Aqueous Mixtures of Cationic Hydroxyethyl Cellulose and Different Anionic Bile Salts.

It is known that the reduction of blood cholesterol can be accomplished through foods containing a large number of dietary fibers; this process is partially related to the binding of bile salt to fibers. To gain new insights into the interactions between dietary fibers and bile salts, this study investigates the interactions between cationic hydroxyethyl cellulose (catHEC) and sodium deoxycholate (NaDC) or sodium cholate (NaC), which have a similar structure. Turbidity measurements reveal strong interactions between catHEC and NaDC, and under some conditions, macroscopic phase separation occurs.

Glyceraldehyde as an Efficient Chemical Crosslinker Agent for the Formation of Chitosan Hydrogels.

The rheological changes that occur during the chemical gelation of semidilute solutions of chitosan in the presence of the low-toxicity agent glyceraldehyde (GCA) are presented and discussed in detail. The entanglement concentration for chitosan solutions was found to be approximately 0.2 wt.

Structural and Rheological Properties of Temperature-Responsive Amphiphilic Triblock Copolymers in Aqueous Media.

Thermoresponsive amphiphilic biodegradable block copolymers of the type poly(ε-caprolactone-co-lactide)-poly(ethylene glycol)-poly(ε-caprolactone-co-lactide) (PCLA-PEG-PCLA) have great potential for various biomedical applications. In the present study, we have surveyed the effects of PEG spacer length (m = 1000 and 1500), temperature, and polymer concentration on the self-assembling process to form supramolecular structures in aqueous solutions of the PCLA-PEG-PCLA copolymer. This copolymer has a lower critical solution temperature, and the cloud point depends on both concentration and PEG length.

Novel Structural Changes during Temperature-Induced Self-Assembling and Gelation of PLGA-PEG-PLGA Triblock Copolymer in Aqueous Solutions.

The thermoresponsive amphiphilic block copolymer poly(d,l-lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-block-poly(d,l-lactic acid-co-glycolic acid) (PLGA-PEG -PLGA), which exhibits a reversible temperature-induced sol-gel transition at higher polymer concentrations in aqueous solution has attached a great deal of interest because of its potential in biomedical applications. In the present work, the length of the hydrophobic PLGA blocks is kept constant, whereas the length of the hydrophilic PEG block is altered and this variation has a pronounced impact on the phase behavior of the aqueous samples and the structure of the polymer. A short PEG block promotes gelation at a low temperature, whereas a longer PEG block shifts the gelation point to higher temperature.

Characterization of omega-3 tablets.

Omega-3 nutraceuticals are extensively used as health supplements worldwide. Various administration forms for delivery of omega-3 are available. However, the niche omega-3 tablets have so far remained unexplored.

Characterization of oligosaccharide-functionalized hyperbranched poly(ethylene imine) and their complexes with retinol in aqueous solution.

Structure, internal density distribution, and size of hyperbranched poly(ethylene imine) (PEI) functionalized with various amounts of maltose (PEI-Mal) in phosphate buffer were studied by small angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The value of pH was varied in the range from 3 to 9. Virtually no effect of pH on the nanostructure was found in this interval.

Compactible powders of omega-3 and β-cyclodextrin.

Omega-3 fatty acids are used in both nutraceuticals and pharmaceuticals in the form of triglycerides and ethyl esters. Administration forms available for omega-3 include bulk oil, soft gel capsules, emulsions and some powder compositions. Cyclodextrins are substances well known for their ability to encapsulate lipophilic molecules.

The influence of polysorbate 80 on the radiochemical synthesis of a PET tracer in the FASTlab.

Purpose: The aim of current study was to investigate the influence of a common non-ionic surfactant, polysorbate 80 (PS80), on radioactive labelling process of a novel PET tracer, [(18)F]Flutemetamol.

Methods: Ferrous oxidation-xylenol orange (FOX) assay, in addition to UV/VIS and (1)H NMR spectroscopies were applied to characterise the composition of the PS80 solution after storage. Multivariate Curve Resolution (MCR) and PLS analysis was used to establish correlation between quality of the PS80 solution and the RCP obtained after labelling.

Classification of structurally related commercial contrast media by near infrared spectroscopy.

Near infrared spectroscopy (NIRS) is a non-destructive measurement technique with broad application in pharmaceutical industry. Correct identification of pharmaceutical ingredients is an important task for quality control. Failure in this step can result in several adverse consequences, varied from economic loss to negative impact on patient safety.

Sustained release of naltrexone from poly(n-isopropylacrylamide) microgels.

The release of the opioid antagonist naltrexone from neutral poly(N-isopropylacrylamide) (PNIPAAM) microgels and negatively charged PNIPAAM microgels containing acrylic acid groups (PNIPAAM-co-PAA) has been studied at various microgel and drug concentrations. The release curves were found to be well represented by the Weibull equation. The release rates were observed to be dependent on the microgel concentration.

Temperature-responsive cationic block copolymers as nanocarriers for gene delivery.

Cationic block copolymers have been regarded as promising alternatives to the use of viral vectors for gene delivery. In this work, poly(N-isopropylacrylamide)n-block-poly((3-acrylamidopropyl)trimethylammonium chloride)m (PNIPAAMn-b-PAMPTMA(+)m) block copolymers with n=48 or 65 and m=6, 10 or 20 were synthesized and evaluated in terms of their potential for in vitro transfection of HeLa cells. These block copolymers collapse above a phase transition temperature, allowing the entrapment of the DNA molecules they are adsorbed to.

In vitro cytotoxicity of a thermoresponsive gel system combining ethyl(hydroxyethyl) cellulose and lysine-based surfactants.

The cytotoxicity of three lysine-derived surfactants with a gemini-like structure was evaluated on HeLa cells. The half maximal effective concentration (EC(50)) was estimated from the dose-response curves and the values indicated an increase in toxicity with the increase in alkyl chain length. The shorter chain length surfactant (C(6)) was shown to be less cytotoxic than sodium dodecyl sulfate (SDS), and all the lysine-derived surfactants were less toxic than the cationic cetyl trimethylammonium bromide (CTAB).

Strategies for multivariate modeling of moisture content in freeze-dried mannitol-containing products by near-infrared spectroscopy.

Accurate determination of residual moisture content of a freeze-dried (FD) pharmaceutical product is critical for prediction of its quality. Near-infrared (NIR) spectroscopy is a fast and non-invasive method routinely used for quantification of moisture. However, several physicochemical properties of the FD product may interfere with absorption bands related to the water content.

Thermoresponsive hydrogels with low toxicity from mixtures of ethyl(hydroxyethyl) cellulose and arginine-based surfactants.

Ethyl(hydroxyethyl) cellulose (EHEC) is known to form hydrogels in water at elevated temperatures in the presence of an ionic surfactant. In this paper, the potential use of arginine-based surfactants is explored considering the production of a low toxicity thermoresponsive hydrogel for pharmaceutical and biomedical applications. The interactions between EHEC and the monomeric surfactant N(α)-lauroyl-L-arginine methyl ester (LAM) and two gemini surfactants N(α),N(ω)-bis(N(α)-acylarginine) α,ω-dialkyl amides were evaluated by Rheo-Small Angle Light Scattering measurements.

Influence of liposomal formulation variables on the interaction with Candida albicans in biofilm; a multivariate approach.

Candida albicans is a species commonly associated with biofilm formation. The aim of this study was to identify liposomal formulation variables influencing the adhesion of liposomes to C. albicans in biofilm.

Immersion coating of pellet cores consisting of chitosan and calcium intended for colon drug delivery.

Biopolymers such as pectin, alginate, and chitosan have a great potential in colon drug delivery. The aim of this study was to produce pellets with calcium and chitosan in the core and then by an interfacial complexation reaction coat the cores with pectin or alginate in combination with calcium or chitosan. Pellets with calcium in the core acted as a reference.

Mucoadhesion and drug permeability of free mixed films of pectin and chitosan: an in vitro and ex vivo study.

The objective of this study was to identify the important factors for the drug permeability and mucoadhesion of casted free pectin/chitosan combination films. The factors varied were: the type of pectin (low and high methoxyl pectin) and the ratio pectin:chitosan (25:75, 50:50 and 75:25). The model drug used for measuring drug permeability was paracetamol.

Effect of pectin type and plasticizer on in vitro mucoadhesion of free films.

The objective was to measure and compare the specific and general mucin interaction of plasticized and unplasticized pectin films. The pectin types differed in the type and degree of substitution. Mucoadhesive properties were measured by using a texture analyzer.

In vitro measurements of mucoadhesive properties of six types of pectin.

The objective of this study was to measure and compare the specific- and general mucin interaction of six pectin types from three manufacturers, differing mainly in the degree of methoxylation and degree of amidation. Mucoadhesive properties were measured using a texture analyzer. It was found that an intermediate degree of methoxylation (35 and 36%) improved the specific mucin interaction.

Multivariate toxicity screening of liposomal formulations on a human buccal cell line.

The influence of various formulation factors on the in vitro cellular toxicity of liposomes on human buccal cells (TR146), were studied by using the concept of statistical experimental design and multivariate evaluation. The factors investigated were the type of main phospholipid (egg-PC, DMPC, DPPC), lipid concentration, the type of charge, liposome size, and amount and nature of the charged component (diacyl-PA, diacyl-PG, diacyl-PS, stearylamine (SA), diacyl-TAP) in the liposomes. Both full factorial design and D-optimal designs were created.

Immersion coating of pellets with calcium pectinate and chitosan.

This study has investigated the potential of immersion coating calcium containing pellet cores first with pectin, and then with two different cross-linkers, calcium or chitosan. The interaction between pectin and calcium, and between pectin and chitosan, are believed to slow down the drug release, and thereby, the coated pellets might possibly be used for colon specific drug delivery. Both the calcium coated pellets and the chitosan coated pellets had a reduced drug release compared to uncoated pellets in 0.

Pectin-based oral drug delivery to the colon.

This review presents an overview of studies concerning oral formulations intended for site-specific drug delivery to the colon with pectin as the main excipient. The biological aspects covered include gastrointestinal transit and the enzymatic degradation of pectin. Scintigraphic methods demonstrating the functionality of pectin formulations are discussed.

Disintegrating pellets from a water-insoluble pectin derivative produced by extrusion/spheronisation.

Pectinic acid (PA) and microcrystalline cellulose (MCC) as extrusion aiding excipients have been compared. Three different drugs were selected as models: Riboflavin with a very low water solubility, paracetamol and theophylline as drugs with high water-solubility. The drug load was varied from 1 to 80% wt.