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Introduction: Microbial resistance is a severe problem for clinical practice due to misuse of antibiotics that promotes the development of surviving strategies by bacteria and fungi. Microbial cells surrounded by a self-produced polymer matrix, defined as biofilms, are inherently more difficult to eradicate. Biofilms endow bacteria with a unique resistance against antibiotics and other anti-microbial agents and play a crucial role in chronic infection., Areas Covered: Biofilm-associated antimicrobial resistance in the lung and wounds. Existing inhaled therapies for treatment of biofilm-associated lung infections. Role of pharmaceutical nanotechnologies to fight resistant microbes and biofilms., Expert Opinion: The effectiveness of antibiotics has gradually decreased due to the onset of resistance phenomena. The formation of biofilms represents one of the most important steps in the development of resistance to antimicrobial treatment. The most obvious solution for overcoming this criticality would be the discovery of new antibiotics. However, the number of new molecules with antimicrobial activity brought into clinical development has considerably decreased. In the last decades the development of innovative drug delivery systems, in particular those based on nanotechnological platforms, has represented the most effective and economically affordable approach to optimize the use of available antibiotics, improving their effectiveness profile. Abbreviations AZT: Aztreonam; BAT: Biofilm antibiotic tolerance; CF: Cystic Fibrosis; CIP: Ciprofloxacin; CRS: Chronic Rhinosinusitis; DPPG: 1,2-dipalmytoyl-sn-glycero-3-phosphoglycerol; DSPC: 1,2-distearoyl-sn-glycero-phosphocholine sodium salt; EPS: extracellular polymeric substance; FEV1: Forced Expiratory Volume in the first second; GSNO: S-nitroso-glutathione; LAE: lauroyl arginate ethyl; MIC: Minimum inhibitory Concentration; NCFB: Non-Cystic Fibrosis Bronchiectasis; NTM: Non-Tuberculous Mycobacteria; NTM-LD: Non-tuberculous mycobacteria Lung Disease PA: Pseudomonas aeruginosa ; pDMAEMA: poly(dimethylaminoethyl methacrylate);pDMAEMA-co-PAA-co-BMA: poly(dimethylaminoethyl methacrylate)-co-propylacrylic acid-co-butyl methacrylate; PEG: polyethylene glycol; PEGDMA: polyethylene glycol dimethacrylate;PCL: Poly-ε-caprolactone; PLA: poly-lactic acid; PLGA: poly-lactic-co-glycolic acid; PVA: poli-vinyl alcohol; SA: Staphylococcus aureus ; TIP: Tobramycin Inhalation Powder; TIS: Tobramycin Inhalation Solution; TPP: Tripolyphosphate.

Introduction: The oral route still represents the most popular way of administering drugs; nowadays oral administration faces new challenges, in particular with regards to the delivery of APIs that are poorly absorbed and sensitive to degradation such as macromolecules and biotechnological drugs. Nanoparticles are promising tools for the efficient delivery of these drugs to the gastrointestinal tract. Areas covered: Approaches and techniques for the formulation of drugs, with particular focus on the preparation of polysaccharide nanoparticles obtained by non-covalent interactions. Expert opinion: Polysaccharide-based nanoparticulate systems offer the opportunity to address some of the issues posed by biotechnological drugs, as well as by small molecules, with problems of stability/intestinal absorption, by exploiting the capability of the polymer to establish non-covalent bonds with functional groups in the chemical structure of the API. This area of research will continue to grow, provided that these drug delivery technologies will efficaciously be translated into systems that can be manufactured on a large scale under GMP conditions. Industrial scale-up represents the biggest obstacle to overcome in view of the transformation of very promising results obtained on lab scale into medicinal products. To do that, an effort toward the simplification of the process and technologies is necessary.

Introduction: The main target of tissue engineering is the preparation and application of adequate materials for the design and production of scaffolds, that possess properties promoting cell adhesion, proliferation and differentiation. The use of natural polysaccharides, such as chitosan, to prepare hydrogels for wound healing and controlled drug delivery is a research topic of wide and increasing interest. Areas covered: This review presents the latest results and challenges in the preparation of chitosan and chitosan-based scaffold/hydrogel for wound healing applications. A detailed overview of their behavior in terms of controlled drug delivery, divided by drug categories, and efficacy was provided and critically discussed. Expert opinion: The need to establish and exploit the advantages of natural biomaterials in combination with active compounds is playing a pivotal role in the regenerative medicine fields. The challenges posed by the many variables affecting tissue repair and regeneration need to be standardized and adhere to recognized guidelines to improve the quality of evidence in the wound healing process. Currently, different methodologies are followed to prepare innovative scaffold formulations and structures. Innovative technologies such as 3D printing or bio-electrospray are promising to create chitosan-based scaffolds with finely controlled structures with customizable shape porosity and thickness. Chitosan scaffolds could be designed in combination with a variety of polysaccharides or active compounds with selected and reproducible spacial distribution, providing active wound dressing with highly tunable controlled drug delivery.

Release modules of amoxicillin and clarithromycin combined in a single dosage form designed to float in the gastric content and to sustain the intra-gastric concentrations of these two antibiotics used for the eradication of Helicobacter pylori have been studied. The modules having a disc shape with curved bases were formulated as hydrophilic matrices. Two modules of clarithromycin were assembled by sticking the concave base of one module to the concave base of the other, creating an internal void chamber. The final dosage form was a floating assembly of three modules of clarithromycin and two of amoxicillin in which the drug release mechanism did not interfere with the floatation mechanism. The assembled system showed immediate in vitro floatation at pH 1.2, lasting 5 h. The in vitro antibiotics release profiles from individual modules and assembled systems exhibited linear release rate during buoyancy for at least 8 h. The predicted antibiotic concentrations in the stomach maintained for long time levels significantly higher than the respective minimum inhibitory concentrations (MIC). In addition, an in vivo absorption study performed on beagle dogs confirmed the slow release of clarithromycin and amoxicillin from the assembled system during the assembly's permanence in the stomach for at least 4 h.

Introduction: After more than four decades of intense research, oral controlled drug delivery systems (DDSs) still represent a topic of major interest for pharmaceutical scientist and formulators. This can be explained in part by considering the economic value of oral DDSs whose market accounts for more than half of the overall drug delivery market. Polymeric systems based on drug-polymer non-covalent interaction represent a limited, but growing part of the field. Despite the large amount of literature and published reviews covering specific aspects, there is still need for a review of the relevant literature providing a general picture of the topic., Areas Covered: The present review aims at presenting the latest findings in drug-polymer and interpolymer non-covalent interactions in oral controlled delivery while providing a specific perspective and a critical point of view, particularly on the tools and methods used for the study of these DDSs. Four main sections are considered: i) ionic interactions between drugs and polymers; ii) interpolymer complexes; iii) hydrogen bond; and iv) hydrophobic interactions., Expert Opinion: The largest part of the scientific literature deals with systems based on drug-polymer ionic interactions while hydrogen bonding and hydrophobic interaction though, very promising, are more difficult to exploit, and therefore less studied. An accurate and exhaustive representation of the specific role of the chemical functions in establishing predictable interactions between drug and polymers is still required.

Hydrophobic materials, in particular hydrogenated vegetable oils, HVO, are extensively used as coating materials in food and pharmaceutical systems. Correct application of these coatings requires an evaluation of their behaviour as a function of various parameters such as melting temperature, solubility, concentration and/or pH. The purpose of this study was to assess the physico-chemical properties of an HVO in terms of composition, crystallisation, phase transition and polymorphism using a variety of analytical techniques, such as electrospray mass spectrometry (ESI-MS), differential scanning calorimetry (DSC) and X-ray diffraction (XRD). High-resolution ESI-MS allowed establishment of the HVO main composition of long-chain triglycerides (average molecular weight 1183 Da). DSC results showed that thermal history determines the formation of at least two polymorphs of HVO, namely two different crystal forms, assigned as form α, melting point (m.p.) 48 °C, and form β', m.p. 60 °C. A third polymorph, the more thermodynamically stable β-form, having a melting point at 62 °C, is obtained by solution-mediated re-crystallisation. Phase transformation paths were investigated by isothermal DSC experiments, which evidenced that the α-form is kinetically stable at temperatures lower than 25 °C. These data are of particular interest in practical applications such as spray freezing or pan coating where significant heat transfer phenomena are involved.

The purpose of this study was to investigate the physico-chemical characteristics of sucralfate humid gel dried by microwaves, in relation to the residual water content. Differential scanning calorimetry (DSC) allowed for the determination of the water state in sucralfate samples. Fourier-transform infrared (FT-IR) spectroscopy was used to monitor the changes in sucralfate gel structure induced by the microwave drying. A boundary value of total water content for sucralfate gel samples was found at 42% (w/w). Below this value only bound water was present, whereas above this value, the increase in total water was due to free water. In the physical form of gel, the strength of the coordination between sulfate anions and the positively charged aluminum hydroxide was dependent on the residual water content. The study of the sedimentation behavior of water suspensions prepared with dried sucralfate allowed for the evaluation of the retention of gel properties. We found that the microwave drying process affected the sedimentation of sucralfate dried gel suspensions independent of the residual water content: when suspensions were prepared from sucralfate dried gel powders containing more than 42% (w/w) of residual water, the sedimentation ratio was higher than 0.9. The non-gel powder suspension showed a sedimentation ratio of 0.68 +/- 0.02, whereas the sucralfate humid gel suspension did not sediment.

This work was aimed at investigating the preparation of beta-cyclodextrin-microcrystalline cellulose pellets by means of a high-shear mixer, both in the absence or in the presence of ibuprofen as model drug. Drug loading of pellets was accomplished by means of two alternative techniques: 1) solution layering or 2) powder layering. The prepared pellets were characterised in terms of size distribution, shape factor, friability and dissolution rate. The interaction between ibuprofen and beta-cyclodextrin was monitored by Differential Scanning Calorimetry (DSC). Micro Fourier Transform Infrared spectroscopy (MicroFTIR) was applied to determine the distribution of components within each pellet on a micro scale. Pellets with narrow size distribution and containing up to about 90% of BCD were prepared using water as binder. The process yield resulted around 84 and 63% for drug-free and medicate pellets respectively. Drug loaded pellets with favourable technological and biopharmaceutical characteristics can be obtained both by powder or solution layering techniques. The latter proved to be more suitable for producing pellets with high drug contents, reduced friability and high drug dissolution rates.

The topical photochemotherapy of dermatoses with psoralens (PUVA therapy) requires an adequate drug level at the target site (basal epidermis) at the time of UVA radiation. The aim of this work was to enhance 5-methoxypsoralen transport to the basal epidermis, with the goal to shorten the delay between drug application and UVA irradiation. 5-Methoxypsoralen transport through rabbit skin was studied in vitro from topical formulations (water solution, gel. and emulsion). The results obtained show that the use of the emulsion increased the flux through rabbit ear skin, even if partitioning was not favorable. Additionally, the time lag was sensibly reduced, compared with the gel and solution. Furthermore, drug accumulation in human skin in vitro was determined using the thin slicing technique. Human skin accumulation profile was significantly higher for the emulsion, compared with the gel, indicating that the delay between psoralen application and UVA irradiation can be shortened.