Background: The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians. Objectives: To report a multicenter ...real-life experience of a group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer. Methods: We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis. Results: Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed (n = 20), including those patients with concomitant active cancers (n = 14). No adverse effects or dropouts related to guselkumab safety profile were detected. Limitations: Modest sample size and the retrospective nature of the study. Conclusion: Guselkumab not only demonstrates high effectiveness in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.
The treatment of psoriasis in patients with a personal history of cancer is a matter of debate and limited evidence is available to guide clinicians.
To report a multicenter real-life experience of a ...group of patients with psoriasis undergoing treatment with guselkumab and a history of cancer.
We conducted a multicenter retrospective Spanish study enrolling patients with moderate-to-severe plaque psoriasis and neoplasia being treated with guselkumab for their psoriasis.
Twenty patients with moderate-to-severe psoriasis and at least 12 weeks of ongoing treatment were included. For the analysis, a 52 week follow-up period was evaluated in terms of efficacy and safety. Most of the malignancies in these patients were solid tumors. The percentage of patients achieving psoriasis area and severity index ≤3 at week 12 and week 52 was 80% and 87.5%, respectively, whereas 68.8% of patients achieved psoriasis area and severity index ≤1. A 52-week survival rate of 100% in the study population was observed (n = 20), including those patients with concomitant active cancers (n = 14). No adverse effects or dropouts related to guselkumab safety profile were detected.
Guselkumab not only demonstrates high efficacy in treating psoriasis but also exhibits a favorable safety profile in patients with neoplasms.
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Interest in orodispersible films (ODF) is growing day-by-day, since this dosage form overcomes some therapeutic obstacles, such as impaired swallowing, and offers several benefits, ...such as the possibility to adapt the dosing requirements for a subset of patients. As a consequence, technologies to produce ODF have risen attention for possible applications in the development of patient-centric formulations. This review critically discusses current trends in the technology platforms proposed to manufacture ODF, including the innovation and opportunities to produce very small batches in a pharmacy setting. Although the main Pharmacopoeias recommend testing customized dosage forms for quality assurance, pharmaceutical assays are a matter of debate due to the complexity and high cost of conventional methods. Alternatively, non-disruptive online analytic methods can be proposed to assay ODF properties, above all to assure the uniformity of drug content.
Background: As drug-metabolizing enzyme activities are affected by a variety of factors, such as drug-drug interactions, a method to evaluate drug-metabolizing enzyme activities in real time is ...needed. In this study, we developed a novel SPECT imaging probe for evaluation of hepatic CYP2D activity. Methods: Iodine-123- and 125-labeled 4-iodobenzylmequitazine ( 123/125 I-BMQ) was synthesized with high labeling and purity. CYP isozymes involved in the metabolism of 125 I-BMQ in mouse liver microsomes were evaluated, and the utility of 123/125 I-was assessed from biological distribution and SPECT imaging evaluation in normal and CYP2D-inhibited mice. Results: In vitro metabolite analysis using mouse liver microsomes showed that 125 I-BMQ is specifically metabolized by CYP2D. Biological distribution and SPECT imaging of 123/125 I-BMQ in normal mice showed that injection 123/125 I-BMQ accumulated early in the liver and was excreted into the gallbladder and intestines. In CYP2D-inhibited mice, accumulation in the liver was increased, but accumulation in the gallbladder and intestines, the excretory organ, was delayed. Since only metabolites of 125 I-BMQ are detected in bile, visualization and measuring of the accumulation of metabolites over time in the intestine, where bile is excreted, could predict the amount of metabolites produced in the body and evaluate CYP2D activity, which would be useful in determining the dosage of various drugs metabolized by CYP2D. Conclusion: 123/125 I-BMQ is useful as a SPECT imaging probe for comprehensive and direct assessment of hepatic CYP2D activity in a minimally invasive and simple approach.
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Trauma- and disease-related skeletal defects and illnesses are plaguing millions of people especially in an ageing globe. Recently, the convergence of additive manufacturing (AM) and ...bone tissue engineering (BTE) has opened up an era of “Personalized Bone Healthcare”, wherein “design”, “printing”, and “engineering” inputs are judiciously orchestrated to yield custom 3D architected (bio)scaffolds, per relevant AM paradigms, to address biological/pathological complexities of host tissues. In this review, a systematic overview of fundamental theories, recent advances, and future trends in this domain is provided. It starts with a general introduction to BTE and AM, followed by emergent topics, including: (i) the design and choices of biomaterials or bioinks for AM paradigms including acellular 3D printing, 3D bioprinting, 4D (bio)printing, and hierarchical printing; (ii) the utilization of computational tools, design–property relationships, and emerging metamaterial strategies to afford predictive, bionic or smart scaffold geometries; and (iii) the engineering of AM systems, processes, and printed parts, by hardware modification, technology fusion, or material functionalization. The ultimate goal is to produce (bio)scaffolds with customized/biomimetic form (geometry, hierarchy, heterogeneity, cellular microenvironments, etc.) and function. Subsequently, the state‐of‐the‐art orthopedic applications are summarized, covering interweaved frontiers of therapy and repair/regeneration. The convergence of AM and BTE as well as clinical translation are also discussed. Finally, current challenges and foreseeable opportunities are outlined to foster future growth. This panoramic review could provide helpful guidance for the design, development, and adoption of AM-based biomaterials for next-generation bone healthcare.
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The establishment of 3D-printing as manufacturing process for oral solid dosage forms enables new options for the individualized medicine.
The aim of this work was to develop a novel ...drug-printing model using pressure-assisted microsyringe (PAM) technology, which allows the precise dispensing of drug substances.
Printed tablets with different numbers of layers, mimicking different doses for pediatric subgroups, were analyzed regarding mass variation, friability, thickness and disintegration time. Furthermore, the uniformity of dosage units and the dissolution behavior were investigated.
Friability was <0.3% in all cases, which demonstrates the ability of PAM printing to manufacture robust solid dosage. Disintegration results showed the dependency of the disintegration on the number of layers and therefore on the compact mass of polymer. However, all tablets disintegrated within 3 min and fulfilled the requirements of immediate release tablets of the USP and orodispersible tablets according to the Ph. Eur. Results of uniformity dosage units confirmed the successful manufacturing of the intended individualized doses. Drug dissolution appeared to be dependent on the number of layers. An increase of layers resulted in a decrease of the drug release rate. Further, the drug release could be correlated to the surface area/volume (SA/V) ratio.
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3D-printing is a promising tool to pave the way to the widespread adaption of individualized medicine. Several printing techniques have been investigated and introduced to ...pharmaceutical research. Until now, only one 3D-printed medicine is approved on the US market. The medicine is manufactured via drop-on-powder deposition, which uses inkjet printing to jet a liquid binder on a powder bed to create 3D objects. However, inkjet processes are prone to nozzle clogging when binders or active pharmaceutical ingredients (APIs) are included in the printing ink. This renders the formulation development of the ink the most challenging step. In this study, different hydroxypropyl cellulose (HPC) grades were investigated as solid binders in the powder formulation on a commercially available DoP printer. The printed ink only consisted of a water/ethanol mixture. Formulations containing 70% caffeine as model API were developed and tablets printed. It was found that the friability of the tablets greatly depends on the particle size of the employed binder, whereas disintegration time and dissolution properties mainly depend on the viscosity of the employed binders. Higher viscous binders led to slower disintegration and dissolution whereas lower viscous binders led to faster disintegration and dissolution. The study demonstrates that HPC is a suitable solid binder for DoP printing and that 3D-DoP printing can be used to print robust dosage forms.
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Fast and accurate manufacturing of individually tailored solid dosage forms is one of the main challenges for personalized medicine. The use of 3D printers has recently been studied ...to determine their suitability for personalized drug manufacturing.
In the current work, formulations free of organic solvents were developed for a pressure-assisted microsyringe printing method (PAM). The water soluble polymer polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG) was used as matrix, while levetiracetam (LEV) was used as model drug. Furthermore, the influence of a second polymer, polyvinylpyrrolidone-vinyl acetate copolymer (PVP-PVAc) on the properties of the printed tablets was investigated. Tablets were printed using a 3D-Bioplotter. The printed formulations were analyzed regarding mass variation, friability and thickness. Furthermore, the disintegration behavior and dissolution profile were analyzed. Investigations of the dissolution profiles of printed tablets show that an immediate release of the API could be achieved. For tablets with PVA-PEG the drug is released completely within 10 min while the additional use of PVP-PVAc leads to a slightly delay with a complete release within 20 min. The same trend is observed regarding the disintegration time of printed tablets. Tablets with PVA-PEG disintegrated within 95 ± 10 s while tablets with additional PVP-PVAc disintegrated within 130 ± 20 s.
Friability of <0.5% indicate that the used PAM printing method provides tablets without loss of structural integrity during handling. Furthermore, it could be shown that the production of tablets with a good content uniformity using a 3D Bioplotter is suitable.
Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti‐allergic ...effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.
