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Poor water-solubility remains a typical property of drug candidates in pharmaceutical development pipelines today. Various processes have been developed to increase the solubility, ...dissolution rate, and bioavailability of these active ingredients belonging to biopharmaceutical classification system (BCS) II and IV classifications. Since the early 2000s, nanocrystal delivery and amorphous solid dispersions are more established techniques to overcome the limitations of poorly-water soluble drugs in FDA available products. This article provides an updated review of nanocrystal and amorphous solid dispersion techniques primarily for orally delivered medicaments. The thermodynamic and kinetic theories relative to these technologies are presented along with marketed product evaluations and a survey of commercially relevant scientific literature.
In the race for a safe and effective vaccine against coronavirus disease (COVID)-19, pharmaceutical formulation science plays a critical role throughout the development, manufacturing, distribution, ...and vaccination phases. The proper choice of the type of vaccine, carrier or vector, adjuvant, excipients, dosage form, and route of administration can directly impact not only the immune responses induced and the resultant efficacy against COVID-19, but also the logistics of manufacturing, storing and distributing the vaccine, and mass vaccination. In this review, we described the COVID-19 vaccines that are currently tested in clinical trials and provided in-depth insight into the various types of vaccines, their compositions, advantages, and potential limitations. We also addressed how challenges in vaccine distribution and administration may be alleviated by applying vaccine-stabilization strategies and the use of specific mucosal immune response-inducing, non-invasive routes of administration, which must be considered early in the development process.
The spectra of postoutburst novae display either He+N or Fe II lines as the most prominent non-Balmer lines at maximum light. Spectral diagnostics indicate physical conditions for "He/N" spectra that ...are consistent with their origin in the white dwarf (WD) ejecta, whereas "Fe II" spectra point to their formation in a large circumbinary envelope of gas whose origin is the secondary star. A determining parameter for which of the two types of spectra predominate may be the binary mass ratio M sub(sec)/M sub(WD). The increasing fraction of novae that are observed to be "hybrid" objects, where both classes of spectra appear sequentially, is explained by changing parameters in the two emitting regions during the postoutburst decline. We argue that most novae may be hybrids that show both types of spectra during decline. The emission line intensity ratio O I lambda8446/lambda7773 is suggested as a good density diagnostic for the ejecta, and a finding list of emission lines identified in recent spectroscopic surveys of novae is presented as an aid to future line identification work.
The understanding of deposition of particles in the respiratory tract is of great value to risk assessment of inhalation toxicology and to improve efficiency in drug delivery of inhalation therapies. ...There are three main basic mechanisms of particle deposition based primarily on particle size: inertial impaction, sedimentation and diffusion. The regional deposition in the lungs can be evaluated in regards to the aerodynamic particle size, in which particle density plays a significant role. In this review paper, we first introduce the available imaging techniques to confirm regional deposition of particles in the human respiratory tract, such as planar scintigraphy, single photon emission computed tomography (SPECT) and positron emission tomography (PET). These technologies have widely advanced and consequently benefited the understanding of deposition pattern, although there is a lack of lung dosimetry techniques to evaluate the deposition of nanoparticles. Subsequently, we present a comprehensive review summarizing the evidence available in the literature that confirms the deposition of smaller particles in the smaller airways as opposed to the larger airways.
Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized ...to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.
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► The BXD family of strains is a powerful resource for systems genetics ► We recorded 140 key clinical metabolic parameters in this reference population ► The BXD family varies significantly for glucose tolerance and energy regulation ► Data were analyzed in terms of heritability, sex effect, and genetic determinants
A large panel of isogenic but diverse strains of BXD-type mice were used to study the genetic control of metabolism. One hundred and forty classical phenotypes were generated and analyzed, allowing dissection of complex metaboilic traits and disorders.
Three-dimensional (3D) printing is a promising approach for the stabilization and delivery of non-living biologics. This versatile tool builds complex structures and customized resolutions, and has ...significant potential in various industries, especially pharmaceutics and biopharmaceutics. Biologics have become increasingly prevalent in the field of medicine due to their diverse applications and benefits. Stability is the main attribute that must be achieved during the development of biologic formulations. 3D printing could help to stabilize biologics by entrapment, support binding, or crosslinking. Furthermore, gene fragments could be transited into cells during co-printing, when the pores on the membrane are enlarged. This review provides: (i) an introduction to 3D printing technologies and biologics, covering genetic elements, therapeutic proteins, antibodies, and bacteriophages; (ii) an overview of the applications of 3D printing of biologics, including regenerative medicine, gene therapy, and personalized treatments; (iii) information on how 3D printing could help to stabilize and deliver biologics; and (iv) discussion on regulations, challenges, and future directions, including microneedle vaccines, novel 3D printing technologies and artificial-intelligence-facilitated research and product development. Overall, the 3D printing of biologics holds great promise for enhancing human health by providing extended longevity and enhanced quality of life, making it an exciting area in the rapidly evolving field of biomedicine.
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The metastable β-Ti alloy, Ti-5553, has been heat-treated to permit a determination of the role of the ω phase on non-classical precipitation of the α phase. Thus, samples containing ...the athermal ω phase have been up-quenched to 600°C. The observations made are consistent with the activation of the non-classical, pseudo-spinodal, nucleation mechanism, with the ω phase playing essentially no direct role. The α/β interfacial structures have been shown to exhibit significant degrees of coherency compared with those in conventional α/β alloys, and implications of this on lowering the interfacial energy, and so the activation for nucleation, are discussed.
Mitochondrial stress activates a mitonuclear response to safeguard and repair mitochondrial function and to adapt cellular metabolism to stress. Using a multiomics approach in mammalian cells treated ...with four types of mitochondrial stressors, we identify activating transcription factor 4 (ATF4) as the main regulator of the stress response. Surprisingly, canonical mitochondrial unfolded protein response genes mediated by ATF5 are not activated. Instead, ATF4 activates the expression of cytoprotective genes, which reprogram cellular metabolism through activation of the integrated stress response (ISR). Mitochondrial stress promotes a local proteostatic response by reducing mitochondrial ribosomal proteins, inhibiting mitochondrial translation, and coupling the activation of the ISR with the attenuation of mitochondrial function. Through a trans-expression quantitative trait locus analysis, we provide genetic evidence supporting a role for Fh1 in the control of Atf4 expression in mammals. Using gene expression data from mice and humans with mitochondrial diseases, we show that the ATF4 pathway is activated in vivo upon mitochondrial stress. Our data illustrate the value of a multiomics approach to characterize complex cellular networks and provide a versatile resource to identify new regulators of mitochondrial-related diseases.
Inhaled nanoparticles–An updated review Praphawatvet, Tuangrat; Peters, Jay I.; Williams, Robert O.
International journal of pharmaceutics,
09/2020, Volume:
587
Journal Article
Peer reviewed
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We are providing an update to our previously published review paper on inhaled nanoparticles, thus updating with the most recent reports in the literature. The field of nanotechnology ...may hold the promise of significant improvements in the health and well-being of patients, as well as in manufacturing technologies. The knowledge of the impact of nanomaterials on public health is limited so far. This paper reviews the unique size-controlled properties of nanomaterials, their disposition in the body after inhalation, and the factors influencing the fate of inhaled nanomaterials. The physiology of the lungs makes it an ideal target organ for non-invasive local and systemic drug delivery, especially for protein and poorly water-soluble drugs that have low oral bioavailability via oral administration. More recently, inhaled nanoparticles have been reported to improve therapeutic efficacies and decrease undesirable side effects via pulmonary delivery. The potential application of pulmonary drug delivery of nanoparticles to the lungs, specifically in context of published results reported on nanomaterials in environmental epidemiology and toxicology is reviewed in this paper. This article presents updated delivery systems, process technologies, and potential of inhaled nanoparticles for local and systemic therapies administered to the lungs. The authors acknowledge the contributions of Wei Yang in our 2008 paper published in this journal.
The dire need for safe and effective coronavirus disease (COVID-19) vaccines is met with many vaccine candidates being evaluated in pre-clinical and clinical studies. The COVID-19 vaccine candidates ...currently in phase 3 or phase 2/3 clinical trials as well as those that recently received emergency use authorization (EUA) from the United States Food and Drug Administration (FDA) and/or other regulatory agencies worldwide require either cold (i.e., 2–8°C) or even freezing temperatures as low as −70°C for storage and distribution. Thus, existing cold chain will struggle to support both the standard national immunization programs and COVID-19 vaccination. The requirement for cold chain is now a major challenge towards worldwide rapid mass vaccination against COVID-19. In this commentary, we stress that thermostabilizing technologies are available to enable cold chain-free vaccine storage and distribution, as well as potential needle-free vaccination. Significant efforts on thermostabilizing technologies must now be applied on next-generation COVID-19 vaccines for more cost-effective worldwide mass vaccination and COVID-19 eradication.
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