Molecularly imprinted intelligent scaffolds for tissue engineering applications

The development of molecularly imprinted polymers (MIPs) using biocompatible production methods enables the possibility to further exploit this technology for biomedical applications. Tissue engineering (TE) approaches use the knowledge of the wound healing process to design scaffolds capable of modulating cell behavior and promote tissue regeneration. Biomacromolecules bear great interest for TE, together with the established recognition of the extracellular matrix, as an important source of signals to cells, both promoting cellâ cell and cellâ matrix interactions during the healing process. This review focuses on exploring the potential of protein molecular imprinting to create bioactive scaffolds with molecular recognition for TE applications based on the most recent approaches in the field of molecular imprinting of macromolecules. Considerations regarding essential components of molecular imprinting technology will be addressed for TE purposes. Molecular imprinting of biocompatible hydrogels, namely based on natural polymers, is also reviewed here. Hydrogel scaffolds with molecular memory show great promise for regenerative therapies. The first molecular imprinting studies analyzing cell adhesion report promising results with potential applications for cell culture systems, or biomaterials for implantation with the capability for cell recruitment by selectively adsorbing desired molecules.The authors wish to thank Dr. Julia Vela-Ramirez, Ms. Heidi Culver, and Mr. John Clegg for important discussions and suggestions. This work was supported in part by the University of Texas-Portugal Collaborative Research Program, and the Grant UTAP-ICDT/CTM-BIO/0023/2014. M.E.W. is supported by a National Science Foundation Graduate Research Fellowship

Progressive ataxia with oculo-palatal tremor and optic atrophy

The final publication is available at Springer via doi: 10.​1007/​s00415-013-7136-

Controlled release from zein matrices: Interplay of drug hydrophobicity and pH

Purpose: In earlier studies, the corn protein zein is found to be suitable as a sustained release agent, yet the range of drugs for which zein has been studied remains small. Here, zein is used as a sole excipient for drugs differing in hydrophobicity and isoelectric point: indomethacin, paracetamol and ranitidine. Methods: Caplets were prepared by hot-melt extrusion (HME) and injection moulding (IM). Each of the three model drugs were tested on two drug loadings in various dissolution media. The physical state of the drug, microstructure and hydration behaviour were investigated to build up understanding for the release behaviour from zein based matrix for drug delivery. Results: Drug crystallinity of the caplets increases with drug hydrophobicity. For ranitidine and indomethacin, swelling rates, swelling capacity and release rates were pH dependent as a consequence of the presence of charged groups on the drug molecules. Both hydration rates and release rates could be approached by existing models. Conclusion: Both the drug state as pH dependant electrostatic interactions are hypothesised to influence release kinetics. Both factors can potentially be used factors influencing release kinetics release, thereby broadening the horizon for zein as a tuneable release agent

Relaxational study of poly(vinylpyrrolidone-co-butyl acrylate) membrane by dielectric and dynamic mechanical spectroscopy

[EN] A poly(vinylpyrrolidone-co-butyl acrylate) (60VP-40BA) membrane is synthesized as a tractable and hydrophilic material, obtaining a water-swelling percentage around 60%. An investigation of molecular mobility by means of differential scanning calorimetry, dynamic mechanical analysis and broadband dielectric relaxation spectroscopy (DRS) is fulfilled in the dry membrane. Dielectric and viscoelastic relaxation measurements are carried out on the 60VP-40BA sample at several frequencies between -150 and 150 degrees C. The dielectric spectrum shows several relaxation processes labelled gamma, beta and alpha in increasing order of temperature, whereas in the mechanical spectrum only the beta and alpha relaxation processes are completely defined. In the dielectric measurements, conductive contributions overlap the alpha-relaxation. The apparent activation energies have similar values for the beta-relaxation in both, the mechanical and the dielectric measurements. The beta process is a Johari-Golstein secondary relaxation and it is related to the local motions of the pyrrolidone group accompanied by the motion of the segments of the polymer backbone. The gamma process is connected with the butyl unit's motions, both located in the side chains of the polymer.BRF, MC, PO and MJS are grateful to CICYT for grant MAT2012-33483. FG and JMG thank the Spanish Ministerio de Economia y Competitividad-FEDER (MAT2011-22544) and the Consejeria de Educacion-Junta de Castilla y Leon (BU001A10-2).Redondo Foj, MB.; Carsí Rosique, M.; Ortiz Serna, MP.; Sanchis Sánchez, MJ.; García, FC.; García. José Miguel (2013). Relaxational study of poly(vinylpyrrolidone-co-butyl acrylate) membrane by dielectric and dynamic mechanical spectroscopy. JOURNAL OF PHYSICS D-APPLIED PHYSICS. 46(29):295304-1-295304-12. https://doi.org/10.1088/0022-3727/46/29/295304S295304-1295304-12462

Izrada i karakterizacija IPN alginatnih i želatinskih mikrogelova s tramadolom: Optimiranje pomoću metode odzivnih površina

Tramadol-loaded interpenetrating polymer network (IPN) alginate-gelatin (AG) microgels (MG) were prepared by the chemical cross-linking technique with glutaraldehyde as cross-linking agent and were optimized using response surfaces. A central composite design for 2 factors, at 3 levels each, was employed to evaluate the effect of critical formulation variables, namely the amount of gelatin (X1) and glutaraldehyde (X2) on geometric mean diameter, encapsulation efficiency, diffusion coefficient (D), amount of mucin adsorbed per unit mass (Qe) and 50 % drug release time (t50). Microgels with average particle size in the range of 44.31102.41 m were obtained. Drug encapsulation up to 86.5 % was achieved. MGs were characterized by FT-IR spectroscopy to assess formation of the IPN structure and differential scanning calorimetry (DSC) was performed to understand the nature of drug dispersion after encapsulation into IPN microgels. Both equilibrium and dynamic swelling studies were performed in pH 7.4 phosphate buffer. Diffusion coefficients and exponents for water transport were determined using an empirical equation. The mucoadhesive properties of MGs were evaluated in aqueous solution by measuring the mucin adsorbed on MGs. Adsorption isotherms were constructed and fitted with Freundlich and Langmuir equations. In vitro release studies indicated the dependence of drug release on the extent of crosslinking and amount of gelatin used in preparing IPNs. The release rates were fitted to power law equation and Higuchi’s model to compute the various drug transport parameters, n value ranged from 0.4055 to 0.5754, suggesting that release may vary from Fickian to quasi-Fickian depending upon variation in the formulation composition.Interpenetrirajući umreženi polimerni (IPN) alginatno-želatinski (AG) mikrogelovi (MG) tramadola pripravljeni su metodom umrežavanja koristeći glutaraldehid kao sredstvo za umrežavanje. Pripravci su optimirani pomoću odzivnih površina. Kompozitini dizajn s dva faktora na tri nivoa upotrijebljen je za procjenu kritičnih formulacijskih varijabli: praćen je utjecaj količine želatine (X1) i glutaraldehida (X2) na prosječnu veličinu čestica, sposobnost kapsuliranja, koeficijent difuzije (D), količinu adsorbiranog mucina po jedinici mase (Qe) i vrijeme potrebno za oslobađanje 50 % lijeka (t50). Dobiveni su mikrogelovi prosječne veličine čestica od 44,31 do 102,41 m, a maksimalno postignuto vezanje lijeka bilo je 86,5 %. Mikrogelovi su karakterizirani FT-IR spektroskopijom i diferencijalnom pretražnom kalorimetrijom (DSC). Ravnotežne i dinamičke studije bubrenja provedene su u fosfatnom puferu pH 7,4. Koeficijenti difuzije i eksponenti za transport vode određeni su pomoću empirijske jednadžbe. Mukoadhezivna svojstva MGs evaluirana su u vodenoj otopini mjerenjem adsorpcije mucina na mikrogelove. Konstruirane su adsorpcijske izoterme i uspoređene s Freudlichovim i Langmuirovim jednadžbama. Pokusi in vitro pokazuju da oslobađanje ljekovite tvari ovisi o stupnju umreženja i količini želatine upotrijebljene u pripravi IPN. Vrijednosti oslobađanja uvrštene su u jednadžbu zakona potencije i u Higuchijev model kako bi se izračunali razni parametri prijenosa lijeka; n vrijednosti bile su između 0,4055 i 0,5754, što ukazuje na to da oslobađanje varira od Fickovog do kvazi-Fickovog, ovisno o sastavu pripravka

Razvoj i vrednovanje plutajućih tableta norfloksacina s produljenim zadržavanjem u želucu

Floating matrix tablets of norfloxacin were developed to prolong gastric residence time, leading to an increase in drug bioavailability. Tablets were prepared by the wet granulation technique, using polymers such as hydroxy propyl methylcellulose (HPMCK4M, HPMCK100M) and xanthan gum. Tablets were evaluated for their physical characteristics viz., hardness, thickness, friability, and mass variation, drug content and floating properties. Further, tablets were studied for in vitro drug release characteristics for 9 hours. The tablets exhibited controlled and prolonged drug release profiles while floating over the dissolution medium. Non-Fickian diffusion was confirmed as the drug release mechanism from these tablets, indicating that water diffusion and the polymer rearrangement played an essential role in drug release. The best formulation (F4) was selected based on in vitro characteristics and was used in vivo radiographic studies by incorporating BaSO4. These studies revealed that the tablets remained in the stomach for 180 ± 30 min in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered desirable for absorption window drugs.Razvijene su plutajuće tablete norfloksacina koje se produljeno zadržavaju u želucu i time povećavaju bioraspoloživost. Tablete su pripravljene metodom vlažne granulacije, koristeći hidroksipropil metilcelulozu (HPMCK4M, HPMCK100M) i ksantan gumu. Tabletama su određena fizikalna svojstva (čvrstoća, debljina, lomljivost i varijacija mase) te sadržaj ljekovite tvari i plutajuća svojstva. Nadalje, praćeno je oslobađanje ljekovite tvari in vitro tijekom 9 h. Uočeno je da je oslobađanje kontrolirano i produljeno te da tablete plutaju u ispitivanom mediju. Mehanizam oslobađanja nije slijedio Fickov zakon, što ukazuje da difuzija vode i promjene u strukturi polimera imaju bitnu ulogu u oslobađanju ljekovite tvari. Najbolja formulacija (F4) in vitro uporabljena je s dodatkom barijevog sulfata za radiografska ispitivanja in vivo. Ispitivanja na volonterima koji su apstinirali od hrane pokazala su da primjena plutajućih tableta produljuje vrijeme zadržavanja u želucu na 180 ± 30 min

Voluntary self-poisoning as a cause of admission to a tertiary hospital internal medicine clinic in Piraeus, Greece within a year

BACKGROUND: Out of 1705 patients hospitalised for various reasons in the 3(rd) Internal Medicine Department of the Regional General Hospital of Nikaea, in Piraeus, 146(8,5%) persons were admitted for drug intoxication between November 1999 and November 2000. METHODS: On average, these persons [male 50(34,2%) – female 96(65,8%)] were admitted to the hospital within 3.7 hours after taking the drug. RESULTS: The drugs that were more frequently taken, alone or in combination with other drugs, were sedatives (67.1%), aspirins and analgesics (mainly paracetamol) (43.5%). 38.3% of patients had a mental illness history, 31.5% were in need of psychiatric help and 45.2% had made a previous suicide attempt. No death occurred during the above period and the outcome of the patients' health was normal. After mental state examination, the mental illnesses diagnosed were depression (20.96%), psychosis (15.32%), dysthymic disorder (16,2%), anxiety disorder (22.58%) and personality disorder (8.87%). CONCLUSIONS: Self-poisoning remains a crucial problem. The use of paracetamol and sedatives are particularly important in the population studied. Interpersonal psychiatric therapy may be a valuable treatment after people tried to poison themselves

Synergistic and competitive aspects of the adsorption of Poly(ethylene glycol) and Poly(vinyl alcohol) onto Na-Bentonite

Graph Presented) The competitive adsorption of poly(ethylene glycol) (PEG) and poly(vinyl alcohol) (PVOH) onto Na-bentonite has been assessed quantitatively. Particular emphasis was focused on the amount of organic located within the bentonite interlayer and any subsequent eff ects on the extent of layer expansion. The individual isotherms showed strong adsorption for both PVOH and PEG at amounts lower than the quantities required to produce a fully loaded bilayer (0.33 g of PVOH/g of clay) and single layered structures (0.10 g of PEG/g of clay), respectively. Above these concentrations, the incremental amounts adsorbed were smaller, and the concentration of adsorbates in solution gradually increased. Na-bentonite adsorbed more PVOH than PEG at any given concentration. In the competitive study, the amount of PVOH adsorbed was enhanced in the presence of PEG (0.10 and 0.30 g/g of clay), but less PEG was adsorbed. At low loadings of PVOH (0.02-0.10 g/g of clay), the amount of adsorbed PEG was increased but at higher PVOH levels PEG adsorption was reduced. The XRD data showed stepped changes in the d-spacing as the adsorbed amounts of both PEG and PVOH increased. The PEG-bentonite samples did not expand beyond a bilayer structure (18 A˚), but the XRD data for PVOH-treated samples indicated the formation of multilayer structures (d ≥ 44 A˚)

Diffusion in Model Networks as Studied by NMR and Fluorescence Correlation Spectroscopy

We have studied the diffusion of small solvent molecules (octane) and larger hydrophobic dye probes in octane-swollen poly(dimethyl siloxane) linear-chain solutions and end-linked model networks, using pulsed-gradient nuclear magnetic resonance (NMR) and fluorescence correlation spectroscopy (FCS), respectively, focusing on diffusion in the bulk polymer up to the equilibrium degree of swelling of the networks, that is, 4.8 at most. The combination of these results allows for new conclusions on the feasibility of different theories describing probe diffusion in concentrated polymer systems. While octane diffusion shows no cross-link dependence, the larger dyes are increasingly restricted by fixed chemical meshes. The simple Fujita free-volume theory proved most feasible to describe probe diffusion in linear long-chain solutions with realistic parameters, while better fits were obtained assuming a stretched exponential dependence on concentration. Importantly, we have analyzed the cross-link specific effect on probe diffusion independently of any specific model by comparing the best-fit interpolation of the solution data with the diffusion in the networks. The most reasonable description is obtained by assuming that the cross-link effect is additive in the effective friction coefficient of the probes. The concentration dependences as well as the data compared at the equilibrium degrees of swelling indicate that swelling heterogeneities and diffusant shape have a substantial influence on small-molecule diffusion in networks.