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Drug Delivery and Translational Research Oct 2023The nebulization of alpha-1 antitrypsin (AAT) for its administration to the lung could be an interesting alternative to parenteral infusion for patients suffering from...
The nebulization of alpha-1 antitrypsin (AAT) for its administration to the lung could be an interesting alternative to parenteral infusion for patients suffering from AAT genetic deficiency (AATD). In the case of protein therapeutics, the effect of the nebulization mode and rate on protein conformation and activity must be carefully considered. In this paper two types of nebulizers, i.e., a jet and a mesh vibrating system, were used to nebulize a commercial preparation of AAT for infusion and compared. The aerosolization performance, in terms of mass distribution, respirable fraction, and drug delivery efficiency, as well as the activity and aggregation state of AAT upon in vitro nebulization were investigated. The two nebulizers demonstrated equivalent aerosolization performances, but the mesh nebulizer provided a higher efficiency in the delivery of the dose. The activity of the protein was acceptably preserved by both nebulizers and no aggregation or changes in its conformation were identified. This suggests that nebulization of AAT represents a suitable administration strategy ready to be translated to the clinical practice for delivering the protein directly to the lungs in AATD patients, either as a support therapy to parenteral administration or for subjects with a precocious diagnosis, to prevent the onset of pulmonary symptoms.
Topics: Humans; Aerosols; Nebulizers and Vaporizers; Drug Delivery Systems; Lung
PubMed: 37097606
DOI: 10.1007/s13346-023-01346-3 -
International Journal of Pharmaceutics Mar 2024Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may...
Multiple-unit dosage forms prepared by compacting pellets offer important manufacturing and compliance advantages over pellet-filled capsules. However, compaction may negatively affect the release control mechanism of pellets, and subunits may not be readily available after intake. Application of a cushioning layer to the starting units is here proposed as a strategy to obtain tablets with satisfactory mechanical strength, rapid disintegration and maintenance of the expected release profile of individual subunits while avoiding the use of mixtures of pellets and excipients to promote compaction and limit the impact of the forces involved. Cushion-coating with PEG1500, a soft and soluble material, was proved feasible provided that the processing temperature was adequately controlled. Cushioned gastro-resistant pellets were shown to consolidate under relatively low compaction pressures, which preserved their inherent release performance after tablet disintegration. Adhesion problems associated with the use of PEG1500 were overcome by applying an outer Kollicoat® IR film. Through design of experiment (DoE), robustness of the proposed approach was demonstrated, and the formulation as well as tableting conditions were optimized. The tableted cushion-coated pellet systems manufactured would allow a relatively high load of modified-release units to be conveyed, thus setting out a versatile and scalable approach to oral administration of multiple-unit dosage forms.
Topics: Excipients; Delayed-Action Preparations; Drug Implants; Tablets; Administration, Oral
PubMed: 38316318
DOI: 10.1016/j.ijpharm.2024.123874 -
BMC Oral Health Sep 2023Dental procedures involving drilling and grinding can produce a significant amount of suspended aerosol particles (PM) and bioaerosols. This study aims to analyze the...
BACKGROUNDS
Dental procedures involving drilling and grinding can produce a significant amount of suspended aerosol particles (PM) and bioaerosols. This study aims to analyze the size and concentration of aerosol particles generated during drilling and to investigate the effectiveness of two air exchange systems, namely forceful suction (FS) and air disinfection machines (DM), in removing PM.
METHODS
For this study, 100 extracted permanent teeth were collected and divided into three groups: without suction (n = 50), suction with forceful suction (n = 25), and suction with air disinfection machines (n = 25). The removal rate of suspended aerosol particles was analyzed using particle counters and air data multimeter.
RESULTS
When drilling and grinding were performed without vacuum, 0.75% of the aerosol particles generated were PM2.5-10, 78.25% of total suspended aerosol particles (TSP) were PM2.5, and 98.68% of TSP were PM1. The nanoanalyzer measurements revealed that the aerodynamic diameter of most aerosol particles was below 60 nm, with an average particle diameter of 52.61 nm and an average concentration of 2.6*10 ultrafine aerosol particles. The air change per hour (ACH) was significantly lower in the air disinfection machines group compared to the forceful suction group. Additionally, the number of aerosol particles and mass concentration was significantly lower in the air disinfection machines group compared to the forceful suction group in terms of PM2.5 levels. However, the forceful suction group also reduced the mass concentration in PM10 level than the air disinfection machines group.
CONCLUSION
In conclusion, the air exchange system can reduce the aerosol particles generated during drilling and grinding. Comparing the two air exchange systems, it was found that the air disinfection machines group reduces the number of aerosol particles and mass concentration in PM2.5 levels, while the forceful suction group reduces the mass concentration in PM10 level.
Topics: Humans; Disinfection; Suction; Aerosols; Particulate Matter
PubMed: 37684672
DOI: 10.1186/s12903-023-03369-1 -
Chemical Society Reviews Aug 2023The development of next-generation bioelectronics, as well as the powering of consumer and medical devices, require power sources that are soft, flexible, extensible,... (Review)
Review
The development of next-generation bioelectronics, as well as the powering of consumer and medical devices, require power sources that are soft, flexible, extensible, and even biocompatible. Traditional energy storage devices (typically, batteries and supercapacitors) are rigid, unrecyclable, offer short-lifetime, contain hazardous chemicals and possess poor biocompatibility, hindering their utilization in wearable electronics. Therefore, there is a genuine unmet need for a new generation of innovative energy-harvesting materials that are soft, flexible, bio-compatible, and bio-degradable. Piezoelectric gels or PiezoGels are a smart crystalline form of gels with polar ordered structures that belongs to the broader family of piezoelectric material, which generate electricity in response to mechanical stress or deformation. Given that PiezoGels are structurally similar to hydrogels, they offer several advantages including intrinsic chirality, crystallinity, degree of ordered structures, mechanical flexibility, biocompatibility, and biodegradability, emphasizing their potential applications ranging from power generation to bio-medical applications. Herein, we describe recent examples of new functional PiezoGel materials employed for energy harvesting, sensing, and wound dressing applications. First, this review focuses on the principles of piezoelectric generators (PEGs) and the advantages of using hydrogels as PiezoGels in energy and biomedical applications. Next, we provide a detailed discussion on the preparation, functionalization, and fabrication of PiezoGel-PEGs (P-PEGs) for the applications of energy harvesting, sensing and wound healing/dressing. Finally, this review concludes with a discussion of the current challenges and future directions of P-PEGs.
Topics: Hydrogels; Electric Power Supplies; Electricity; Electronics; Hazardous Substances
PubMed: 37585216
DOI: 10.1039/d3cs00202k -
Advances in Colloid and Interface... Apr 2024A map of stability for various water/oil/pea protein compositions has been plotted from the numerous reported results. Two clear regions of stability were identified.... (Review)
Review
A map of stability for various water/oil/pea protein compositions has been plotted from the numerous reported results. Two clear regions of stability were identified. High internal oil phase emulsions with 70-80%, v/v oil content stabilized by total pea protein concentration <2.5%, w/v showed stability. Low oil content of 10-30%, v/v for a range of total pea protein concentrations >0.5%, w/v have also been identified as stable. Intermediate oil content and pea protein concentrations >4% w/v are unexplored regions and are likely to be areas of fruitful future research. The wide range of stability suggests that different stabilization mechanisms could be important for different compositions and careful consideration has to be taken to avoid oversimplification. Both stabilization with particles, i.e. Pickering emulsions, and protein unfolding have been suggested as mechanisms. The diverse way of describing stability makes it difficult to intercompare results in different studies. A summary of different oil types used have been presented and several properties such as dynamic viscosity, density, the dielectric constant and interfacial tension have been summarized for common vegetable oils. The type of vegetable oil and emulsion preparation techniques were seen to have rather little effect on emulsion stability. However, the different extraction methods and processing of the pea material had more effect, which could be attributed to changing composition of different proteins and to the states of aggregation and denaturing. Careful consideration has to be taken in the choice of extraction method and an increased understanding of what contributes to the stability is desirable for further progress in research and eventual product formulation.
Topics: Emulsions; Pisum sativum; Pea Proteins; Viscosity; Particle Size
PubMed: 38502971
DOI: 10.1016/j.cis.2024.103123 -
International Journal of Pharmaceutics May 2024Parenteral administration is one of the most commonly used drug delivery routes for nanoparticle-based dosage forms, such as lipid-based and polymeric nanoparticles. For... (Review)
Review
Parenteral administration is one of the most commonly used drug delivery routes for nanoparticle-based dosage forms, such as lipid-based and polymeric nanoparticles. For the treatment of various diseases, parenteral administration include intravenous, subcutaneous, and intramuscular route. In drug development phase, multiparameter strategy with a focus on drug physicochemical properties and the specificity of the administration route is required. Nanoparticle properties in terms of size and targeted delivery, among others, are able to surpass many drawbacks of conventional dosage forms, but these unique properties can be a bottleneck for approval by regulatory authorities. Quality by Design (QbD) approach has been widely utilized in development of parenteral nanoparticle-based dosage forms. It fosters knowledge of product and process quality by involving sound scientific data and risk assessment strategies. A full and comprehensive investigation into the state of implementation and applications of the QbD approach in these complex drug products can highlight the gaps and challenges. In this review, the analysis of critical attributes and Design of Experiment (DoE) approach in different nanoparticulate systems, together with the proper utilization of Process Analytical Technology (PAT) applications are described. The essential of QbD approach for the design and development of nanoparticle-based dosage forms for delivery via parenteral routes is discussed thoroughly.
Topics: Nanoparticles; Humans; Animals; Drug Delivery Systems; Infusions, Parenteral; Dosage Forms; Pharmaceutical Preparations
PubMed: 38670473
DOI: 10.1016/j.ijpharm.2024.124163 -
Molecules (Basel, Switzerland) Jan 2024In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface... (Review)
Review
In recent years, nanocarriers have played an ever-increasing role in clinical and biomedical applications owing to their unique physicochemical properties and surface functionalities. Lately, much effort has been directed towards the development of smart, stimuli-responsive nanocarriers that are capable of releasing their cargos in response to specific stimuli. These intelligent-responsive nanocarriers can be further surface-functionalized so as to achieve active tumor targeting in a sequential manner, which can be simply modulated by the stimuli. By applying this methodological approach, these intelligent-responsive nanocarriers can be directed to different target-specific organs, tissues, or cells and exhibit on-demand controlled drug release that may enhance therapeutic effectiveness and reduce systemic toxicity. Light, an external stimulus, is one of the most promising triggers for use in nanomedicine to stimulate on-demand drug release from nanocarriers. Light-triggered drug release can be achieved through light irradiation at different wavelengths, either in the UV, visible, or even NIR region, depending on the photophysical properties of the photo-responsive molecule embedded in the nanocarrier system, the structural characteristics, and the material composition of the nanocarrier system. In this review, we highlighted the emerging functional role of light in nanocarriers, with an emphasis on light-responsive liposomes and dual-targeted stimuli-responsive liposomes. Moreover, we provided the most up-to-date photo-triggered targeting strategies and mechanisms of light-triggered drug release from liposomes and NIR-responsive nanocarriers. Lastly, we addressed the current challenges, advances, and future perspectives for the deployment of light-responsive liposomes in targeted drug delivery and therapy.
Topics: Humans; Liposomes; Drug Carriers; Nanoparticles; Drug Delivery Systems; Neoplasms
PubMed: 38338380
DOI: 10.3390/molecules29030636 -
International Journal of Pharmaceutics Mar 2024Three-dimensional printing (3DP) is an emerging technology, offering the possibility for the development of dose-customized, effective, and safe solid oral dosage forms... (Review)
Review
Three-dimensional printing (3DP) is an emerging technology, offering the possibility for the development of dose-customized, effective, and safe solid oral dosage forms (SODFs). Although 3DP has great potential, it does come with certain limitations, and the traditional drug manufacturing platforms remain the industry standard. The consensus appears to be that 3DP technology is expected to benefit personalized medicine the most, but that it is unlikely to replace conventional manufacturing for mass production. The 3DP method, on the other hand, could prove well-suited for producing small batches as an adaptive manufacturing technique for enabling adaptive clinical trial design for early clinical studies. The purpose of this review is to discuss recent advancements in 3DP technologies for SODFs and to focus on the applications for SODFs in the early clinical development stages, including a discussion of current regulatory challenges and quality controls.
Topics: Printing, Three-Dimensional; Precision Medicine; Industry; Quality Control; Pharmaceutical Preparations; Technology, Pharmaceutical; Dosage Forms
PubMed: 38360287
DOI: 10.1016/j.ijpharm.2024.123902 -
International Journal of Pharmaceutics Nov 2023A novel subtractive manufacturing method to produce bespoke tablets with immediate and extended drug release is presented. This is the first report on applying fusion...
A novel subtractive manufacturing method to produce bespoke tablets with immediate and extended drug release is presented. This is the first report on applying fusion laser cutting to produce bespoke furosemide solid dosage forms based on pharmaceutical-grade polymeric carriers. Cylindric tablets of different sizes were produced by controlling the two-dimensional design of circles of the corresponding diameter. Immediate and extended drug release patterns were achieved by modifying the composition of the polymeric matrix. Thermal analysis and XRD indicated that furosemide was present in an amorphous form. The laser-cut tablets demonstrated no significant drug degradation (<2%) nor the formation of impurities were identified. Multi-linear regression was used to quantify the influences of laser-cutting process parameters (laser energy levels, scan speeds, and the number of laser applications) on the depth of the laser cut. The utility of this approach was exemplified by manufacturing tablets of accurate doses of furosemide. Unlike additive or formative manufacturing, the reported approach of subtractive manufacturing avoids the modification of the structure, e.g., the physical form of the drug or matrix density of the tablet during the production process. Hence, fusion laser cutting is less likely to modify critical quality attributes such as release patterns or drug contents. In a point-of-care manufacturing scenario, laser cutting offers a significant advantage of simplifying quality control and a real-time release of laser-cut products such as solid dosage forms and implants.
Topics: Technology, Pharmaceutical; Furosemide; Point-of-Care Systems; Tablets; Drug Liberation; Polymers; Printing, Three-Dimensional
PubMed: 37852311
DOI: 10.1016/j.ijpharm.2023.123518 -
Science Advances Oct 2023Human-induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in...
Human-induced pluripotent stem cells (hiPSCs) have emerged as a promising in vitro model system for studying neurodevelopment. However, current models remain limited in their ability to incorporate tunable biomechanical signaling cues imparted by the extracellular matrix (ECM). The native brain ECM is viscoelastic and stress-relaxing, exhibiting a time-dependent response to an applied force. To recapitulate the remodelability of the neural ECM, we developed a family of protein-engineered hydrogels that exhibit tunable stress relaxation rates. hiPSC-derived neural progenitor cells (NPCs) encapsulated within these gels underwent relaxation rate-dependent maturation. Specifically, NPCs within hydrogels with faster stress relaxation rates extended longer, more complex neuritic projections, exhibited decreased metabolic activity, and expressed higher levels of genes associated with neural maturation. By inhibiting actin polymerization, we observed decreased neuritic projections and a concomitant decrease in neural maturation gene expression. Together, these results suggest that microenvironmental viscoelasticity is sufficient to bias human NPC maturation.
Topics: Humans; Hydrogels; Extracellular Matrix; Neurogenesis; Neural Stem Cells
PubMed: 37862423
DOI: 10.1126/sciadv.adh8313