Poly(ɛ-caprolactone) (PCL) is a biocompatible, biodegradable, and highly mechanically resilient FDA-approved material (for specific biomedical applications, e.g. as drug delivery devices, in sutures, or as an adhesion barrier), rendering it a promising candidate to serve bone tissue engineering. However, in vivo monitoring of PCL-based implants, as well as biodegradable implants in general, and their degradation profiles pose a significant challenge, hindering further development in the tissue engineering field and subsequent clinical adoption. To address this, photo-cross-linkable mechanically resilient PCL networks are developed and functionalized with a radiopaque monomer, 5-acrylamido-2,4,6-triiodoisophthalic acid (AATIPA), to enable non-destructive in vivo monitoring of PCL-based implants. The covalent incorporation of AATIPA into the crosslinked PCL networks does not significantly affect their crosslinking kinetics, mechanical properties, or thermal properties, but it increases their hydrolysis rate and radiopacity. Complex and porous 3D designs of radiopaque PCL networks can be effectively monitored in vivo. This work paves the way toward non-invasive monitoring of in vivo degradation profiles and early detection of potential implant malfunctions.
- MeSH
- biokompatibilní materiály chemie MeSH
- myši MeSH
- polyestery * chemie MeSH
- poréznost MeSH
- testování materiálů MeSH
- tkáňové inženýrství metody MeSH
- tkáňové podpůrné struktury * chemie MeSH
- vstřebatelné implantáty MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
This study develops and characterizes novel biodegradable soft hydrogels with dual porosity based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers cross-linked by hydrolytically degradable linkers. The structure and properties of the hydrogels are designed as scaffolds for tissue engineering and they are tested in vitro with model mesenchymal stem cells (rMSCs). Detailed morphological characterization confirms dual porosity suitable for cell growth and nutrient transport. The dual porosity of hydrogels slightly improves rMSCs proliferation compared to the hydrogel with uniform pores. In addition, the laminin coating supports the adhesion of rMSCs to the hydrogel surface. However, hydrogels modified by heptapeptide RGDSGGY significantly stimulate cell adhesion and growth. Moreover, the RGDS-modified hydrogels also affect the topology of proliferating rMSCs, ranging from single-cell to multicellular clusters. The 3D reconstruction of the hydrogels with cells obtained by laser scanning confocal microscopy (LSCM) confirms cell penetration into the inner structure of the hydrogel and its corresponding microstructure. The prepared biodegradable oligopeptide-modified hydrogels with dual porosity are suitable candidates for further in vivo evaluation in soft tissue regeneration.
BACKGROUND: Surgical site infection (SSI) is the most consistently reported complication of cranioplasty. No material showed a categorical superiority in the incidence of infection. Porous polyethylene (PE) is considered a low risk material regarding SSI. However, the literature data are very limited. Thus, our objective was to verify the assumed low incidence of SSI after PE cranioplasty in patients at high risk of SSI. The primary objective was the infection rate, while secondary objectives were implant exposure, revision and cosmetic results. METHOD: Patients who underwent three-dimensional (3D) personalized PE cranioplasty in the period 2014-2023 were evaluated prospectively. Only patients with an increased risk of SSI, and a satisfactory clinical conditions were included in the study. RESULTS: Thirty procedures were performed in 30 patients. Cranioplasty was performed 23 times after hemispheric decompressive craniectomy, five times after limited size craniotomy and two times after bifrontal decompressive craniectomy. Risk factors for the development of infection were 18 previous SSIs, 16 previous repeated revision surgeries, four intraoperatively opened frontal sinuses and two times radiotherapy. Neither infection nor implant exposure was detected in any patient. All patients were satisfied with the aesthetic result. In two cases, a revision was performed due to postoperative epidural hematoma. CONCLUSIONS: Three-dimensional personalized PE cranioplasty is associated with an extremely low incidence of SSI even in high-risk patients. However, our conclusions can only be confirmed in larger studies.
- MeSH
- dekompresní kraniektomie škodlivé účinky metody MeSH
- dospělí MeSH
- infekce chirurgické rány * epidemiologie etiologie MeSH
- kraniotomie škodlivé účinky metody MeSH
- lebka chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- polyethylen MeSH
- poréznost MeSH
- prospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- zákroky plastické chirurgie * metody škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Platinum is the most widespread electrode material used for implantable biomedical and neuroelectronic devices, motivating exploring ways to improve its performance and understand its fundamental properties. Using reactive magnetron sputtering, PtOx is prepared, which upon partial reduction yields a porous thin-film form of platinum with favorable properties, notably record-low impedance values outcompeting other reports for platinum-based electrodes. It is established that its high electrochemical capacitance scales with thickness, in the way of volumetric capacitor materials like IrOx and poly(3,4-ethylenedioxythiophene), PEDOT. Unlike these two well-known analogs, however, it is found that PtOx capacitance is not caused by reversible pseudofaradaic reactions but rather due to high surface area. In contrast to IrOx, PtOx is not a reversible valence-change oxide, but rather a porous form of platinum. The findings show that this oxygen-containing form of Pt can place Pt electrodes on a level competitive with IrOx and PEDOT. Due to its relatively low cost and ease of preparation, PtOx can be a good choice for microfabricated bioelectronic devices.
Inhalation drug administration is increasingly used for local pharmacotherapy of lung disorders and as an alternative route for systemic drug delivery. Modern inhalation powder systems aim to target drug deposition in the required site of action. Large porous particles (LPP), characterized by an aerodynamic diameter over 5 μm, density below 0.4 g/cm3, and the ability to avoid protective lung mechanisms, come to the forefront of the research. They are mostly prepared by spray techniques such as spray drying or lyophilization using pore-forming substances (porogens). These substances could be gaseous, solid, or liquid, and their selection depends on their polarity, solubility, and mutual compatibility with the carrier material and the drug. According to the pores-forming mechanism, porogens can be divided into groups, such as osmogens, extractable porogens, and porogens developing gases during decomposition. This review characterizes modern trends in the formulation of solid microparticles for lung delivery; describes the mechanisms of action of the most often used porogens, discusses their applicability in various formulation methods, emphasizes spray techniques; and documents discussed topics by examples from experimental studies.
- MeSH
- aplikace inhalační MeSH
- farmaceutická chemie metody MeSH
- lékové transportní systémy * metody MeSH
- lidé MeSH
- plíce * metabolismus účinky léků MeSH
- poréznost MeSH
- prášky, zásypy, pudry MeSH
- příprava léků metody MeSH
- velikost částic * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Periodontal disease is a significant burden for oral health, causing progressive and irreversible damage to the support structure of the tooth. This complex structure, the periodontium, is composed of interconnected soft and mineralised tissues, posing a challenge for regenerative approaches. Materials combining silicon and lithium are widely studied in periodontal regeneration, as they stimulate bone repair via silicic acid release while providing regenerative stimuli through lithium activation of the Wnt/β-catenin pathway. Yet, existing materials for combined lithium and silicon release have limited control over ion release amounts and kinetics. Porous silicon can provide controlled silicic acid release, inducing osteogenesis to support bone regeneration. Prelithiation, a strategy developed for battery technology, can introduce large, controllable amounts of lithium within porous silicon, but yields a highly reactive material, unsuitable for biomedicine. This work debuts a strategy to lithiate porous silicon nanowires (LipSiNs) which generates a biocompatible and bioresorbable material. LipSiNs incorporate lithium to between 1% and 40% of silicon content, releasing lithium and silicic acid in a tailorable fashion from days to weeks. LipSiNs combine osteogenic, cementogenic and Wnt/β-catenin stimuli to regenerate bone, cementum and periodontal ligament fibres in a murine periodontal defect.
- MeSH
- beta-katenin * MeSH
- křemík farmakologie MeSH
- kyselina křemičitá farmakologie MeSH
- lithium farmakologie MeSH
- myši MeSH
- nanodráty * MeSH
- poréznost MeSH
- zubní cement (tkáň) MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Drug loading into mesoporous carriers may help to improve the dissolution of poorly aqueous-soluble drugs. However, both preparation method and carrier properties influence loading efficiency and drug release. Accordingly, this study aimed to compare two preparation methods: formulation into liquisolid systems (LSS) and co-milling for their efficiency in loading the poorly soluble model drug cyclosporine A (CyA) into mesoporous magnesium aluminometasilicate Neusilin® US2 (NEU) or functionalized calcium carbonate (FCC). Scanning electron microscopy was used to visualize the morphology of the samples and evaluate the changes that occurred during the drug loading process. The solid-state characteristics and physical stability of the formulations, prepared at different drug concentrations, were determined using X-ray powder diffraction. In vitro release of the drug was evaluated in biorelevant media simulating intestinal fluid. The obtained results revealed improved drug release profiles of the formulations when compared to the milled (amorphous) CyA alone. The dissolution of CyA from LSS was faster in comparison to the co-milled formulations. Higher drug release was achieved from NEU than FCC formulations presumably due to the higher pore volume and larger surface area of NEU.
- MeSH
- difrakce rentgenového záření MeSH
- pomocné látky * MeSH
- poréznost MeSH
- rozpustnost MeSH
- voda * MeSH
- Publikační typ
- časopisecké články MeSH
Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.
- MeSH
- 3D tisk * MeSH
- farmaceutická technologie metody MeSH
- flukonazol * MeSH
- poréznost MeSH
- tablety chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
There is increasing research interest in using mesoporous silica for the delivery of poorly water-soluble drugs that are stabilized in a noncrystalline form. Most research has been done on ordered silica, whereas far fewer studies have been published on using nonordered mesoporous silica, and little is known about intrinsic drug affinity to the silica surface. The present mechanistic study uses inverse gas chromatography (IGC) to analyze the surface energies of three different commercially available disordered mesoporous silica grades in the gas phase. Using the more drug-like probe molecule octane instead of nitrogen, the concept of a "drug-accessible surface area" is hereby introduced, and the effect on drug monolayer capacity is addressed. In addition, enthalpic interactions of molecules with the silica surface were calculated based on molecular mechanics, and entropic energy contributions of volatiles were estimated considering molecular flexibility. These free energy contributions were used in a regression model, giving a successful comparison with experimental desorption energies from IGC. It is proposed that a simplified model for drugs based only on the enthalpic interactions can provide an affinity ranking to the silica surface. Following this preformulation research on mesoporous silica, future studies may harness the presented concepts to guide formulation scientists.
- MeSH
- léčivé přípravky MeSH
- oxid křemičitý * chemie MeSH
- poréznost MeSH
- rozpustnost MeSH
- voda * chemie MeSH
- Publikační typ
- časopisecké články MeSH
Inhalační podání suchých práškových částic je využívanou aplikační cestou pro dosažení lokálního i systémového působení léčiv. U plicních onemocnění je žádoucí depozice léčiv v místě účinku. Pro efektivní léčbu jsou tak zásadní parametry inhalovaných částic, a to především jejich velikost, tvar nebo aerosolizační parametry. Vhodných parametrů je možné dosáhnout volbou metody přípravy nebo pomocných látek (nosičů, porogenů nebo aerosolizačních činidel). Cílem experimentu byla příprava jedenácti šarží práškových směsí sprejovým sušením, které se lišily použitým nosičem, množstvím leucinu či porogenu. Cílem bylo optimalizovat složení pro navázání léčiva s ohledem na požadavky pro plicní podání. Připravené částice byly zhodnoceny z hlediska morfologie, tokových vlastností, pórovitosti, geometrického i aerodynamického průměru. Bylo zjištěno, že se zvyšující se koncentrací leucinu se sypná hustota částic snižovala a zároveň rostla hodnota FPF. Stejně tak docházelo i ke snižování MMAD. Jako vhodná se jevila šarže obsahující 15 % leucinu. Při stanovení optimální koncentrace porogenu (hydrogenuhličitan amonný) u manitolových částic dosahovala nejlepších výsledků šarže s jeho 1% zastoupením, vzhledem k vyhovující velikosti částic oproti ostatním šaržím (MMAD 5,92 ± 1,32 μm), vhodné pórovitosti a obecně přijatelné morfologii částic. Za účelem formulace částic s navázaným léčivem by tedy bylo vhodné snížit aerodynamický průměr částic např. úpravou procesních parametrů sprejového sušení.
Inhalation administration of dry powder particles is a common application route to achieve local and systemic drug effects. For pulmonary diseases, the deposition of drugs at the site of action is desirable. Thus, the parameters of the inhaled particles, especially their size, shape, or aerosolization, are essential for effective treatment. Suitable parameters can be achieved by choice of preparation method or excipients (carriers, porogens, or aerosolizing agents). This experiment aimed to prepare 11 batches of powder mixtures by spray drying, which differed in the carrier used and the amount of leucine or porogen. The aim was to optimize the formulation for drug binding concerning the requirements for pulmonary administration. The prepared particles were evaluated in terms of morphology, flow properties, porosity, and geometric and aerodynamic diameter. It was found that with increasing concentration of leucine, the bulk density of the particles decreased while the FPF value increased. Similarly, there was a decrease in MMAD. The batch containing 15% leucine was the most suitable. In determining the optimum porogen concentration for mannitol particles, the batch with its 1% gave the best results due to its adequate particle size compared to the other batches (MMAD 5.92 ± 1.32 μm), suitable porosity, and particle morphology. Thus, to formulate drug-loaded particles, it would be advisable to reduce the aerodynamic diameter of the particles, e.g., by spray drying process parameters.
