176 research outputs found
Translational Control in Tumour Progression and Drug Resistance
Protein biosynthesis is a multi-step process that starts with the transcription of nuclear
DNA, depository of genetic information, into messenger RNA (mRNA) that is used as
template for the following polypeptide chain synthesis, also known as translation. Each step
of this essential process is highly controlled in order to modulate any specific protein
requirement of the cell in response to different stimuli and cellular events. This regulatory
process is called translational control. Deregulation of the core signalling network in
translational control, the phosphatidyl inositol trisphosphate kinase (PI3K), Protein Kinase B
(PKB or Akt), mammalian target of rapamycin (mTOR) and RAS mitogen-activated protein
kinase (MAPK)/MAPK-interacting Kinases (MNK) pathways, frequently occurs in human
cancers and leads to aberrant modulation of mRNA translation. However, investigations on
the contribution of these two pathways to translational regulation led to the interesting
finding that translation factors are also substrate of signalling molecules. Post-translational
modifications, including cleavage and phosphorylation, usually affect translational factors
activity in protein biosynthesis; on the other hand, direct interaction of translational
components with signalling mediators can either activate the pathway in which the
mediator is involved or redirect translation factors to other activities, such as cytoskeletal
rearrangements. These findings shed light on new functions of translation factors, different
from their canonical role in protein synthesis. Taken together, these new functions are an
intriguing step forward to the discovery of molecular mechanisms at the base of cellular
response during âspecialâ conditions such as cancer and drug resistance
Intensifying the microencapsulation process: Ultrasonic atomization as an innovative approach
In this review, new approaches to the microencapsulation processes, widely used in the manufacturing of
pharmaceutical products, are discussed focusing the attention on the emerging ultrasonic atomization
technique. Fundamentals and novel aspects are presented, and advantages of ultrasonic atomization in
terms of intensification and low energy requests are emphasized
In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery
Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract. Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications
Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles
This work presents both the design of a novel process to produce microparticles with a shellâcore structure and a
bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process
intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave
heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying.
Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a
semicontinuous procedure. Basic design criteria and advantages of the ultrasonicâmicrowave coupled operations in the realized
apparatus are presented and discussed. Results of testing and of operating runs to produce shellâcore microparticles are also
reported, emphasizing the main features of the produced particles
Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery
This paper describes the development of pH-sensitive poly(methyl
methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical
products for oral administration. To obtain the dissolution at the desired pH level,
different pH-sensitive polymers are available on the market. Usually, for each
desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH
values could ask for completely different polymers. Instead, the materials proposed
in this work are copolymers of the same two monomers, and the different dissolution
pH was obtained by changing the volume fraction of the hydrophobic methyl
methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the
volumetric percentage of methyl methacrylate causes the polymer to dissolve at
increasing pH, until the dissolution does not take place at all, and it is replaced by a
slow swelling phenomenon. The copolymers obtained were characterized by differential
scanning calorimetry, in order to evaluate their glass transition temperature,
and these latter were related to %MMA. The molecular weights of the pure polymers
(PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass
transition temperatures observed. The dissolution of the copolymers was carefully
tested in buffer solutions for a dense set of pH values. A linear relationship between
dissolution pH and volumetric percentage of methyl methacrylate was obtained from
these measurements. As a result, for any physiological compartment, the copolymer
which dissolves at the pH of interest can be easily synthesized. doi:10.1007/s00289-009-0040-
Analysis and modeling of swelling and erosion behavior for pure HPMC tablet
This work is focused on the transport phenomena which take place during immersion in water of pure hydroxypropylmethylcellulose tablets. The water uptake, the swelling and the erosion during immersion were investigated in drug-free systems, as a preliminary task before to undertake the study of drug-loaded ones. The tablets, obtained by powder compression, were confined between glass slabs to allow water uptake only by lateral surface and then immersed in distilled water at 37 °C, with simultaneous video-recording. By image analysis the normalized light intensity profiles were obtained and taken as a measure of the water mass fraction. The time evolutions of the total tablet mass, of the water mass and of the erosion radius were measured, too. Thus a novel method to measure polymer and water masses during hydration was pointed out. Then, a model consisting in the transient mass balance, accounting for water diffusion, diffusivity change due to hydration, swelling and erosion, was found able to reproduce all experimental data. Even if the model was already used in literature, the novelty of our approach is to compare model predictions with a complete set of experimental data, confirming that the main phenomena were correctly identified and described
Pharmaceutical Applications of Biocompatible Polymer Blends ontaining Sodium Alginate
Biocompatible polymer blends, such as alginate blends, have a
widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic
dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127Âź. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shellâcore particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations).
Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures
An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications
In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scaleâsize. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogelâbased drug delivery systems (macroscopic HBâDDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences
Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters
Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed
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