Slaughtermoesgaard4807

Immunotherapy represents an effective and promising option in various cancers, including in hepatocellular carcinoma (HCC). The immune checkpoint inhibitors (ICIs) have shown a remarkable breakthrough in the last decade, in addition to molecular targeted therapy of angiogenesis such as tyrosine kinases inhibitors. ICIs provide new regimen that can be applied in different stages of the disease. In parallel, HCC progression is related to the tumor microenvironment (TME), involving the cross-talk between various cellular and non-cellular components within the TME niche. It appears logical to synergistically target several HCC components to increase the efficacy of the treatment. In this paper, we summarize evidence that the combination therapy of ICIs and angiogenesis inhibitors would be a potentially better strategy for HCC treatment.This study aims to investigate the effect of physicochemical properties and aerosol performance of two (2FN) and three-fluid nozzles (3FN) on the inhalable co-formulation of tobramycin and diclofenac dry powders. Combination formulations of tobramycin and diclofenac at 21 and 41 w/w ratios were prepared at a laboratory scale using a spray dryer in conjunction with a 2FN or 3FN. selleck inhibitor Powder size, morphology, solid-state characteristics, and aerodynamic and dissolution properties were characterised. The nozzle types and the formulation composition influenced the yield, particle size, solid-state properties, aerosolization behaviour and dissolution of the co-spray dried formulations. In particular, using the 2FN the co-spray dried formulation of tobramycin and diclofenac at 21 w/w showed smaller particle size (D50, 3.01 ± 0.06 μm), high fine particle fractions (FPF) (61.1 ± 3.6% for tobramycin and 65.92 ± 3 for diclofenac) and faster dissolution with approx. 70% diclofenac released within 3 h and approx. 90% tobramycin was released within 45 min. However, the 3FN for the co-spray dried formulation of tobramycin and diclofenac at a 21 w/w ratio showed a larger particle size (D50, 3.42 ± 0.02 μm), lower FPF (40.6 ± 3.4% for tobramycin and 36.9 ± 0.84 for diclofenac) and comparative slower dissolution with approx. 60% diclofenac was released within 3 h and 80% tobramycin was released within 45 min. A similar trend was observed when the tobramycin to diclofenac ratio was increased to 41 w/w. Overall results suggest that spray drying with 2FN showed a superior and viable approach to producing excipients-free inhalable co-spray dried formulations of tobramycin and diclofenac. However, the formulation produced using the 3FN showed higher enrichment of hydrophobic diclofenac and an ability to control the tobramycin drug release in vitro.Pharmaceutical compounding is a core activity in the preparation of patient-specific dosage forms. In the current study we aimed to investigate whether 3D printing could be employed for the preparation of pediatric-friendly personalized dosage forms that fulfil the acceptance criteria specified in the pharmacopoeias for conventional dosage forms. We then compared the 3D printed dosage forms with the same formulations prepared with mold-casting, a method frequently applied during pharmaceutical compounding. The molded dosage forms failed to pass most of the quality control tests, including the mass uniformity and content uniformity tests, as well as dose accuracy, contrary to the 3D printed, which not only passed all tests but also enabled precision overdose adjustment. Hence, 3D printing of chocolate-based dosage forms may effectively serve as an acceptable alternative method to mold casting in compounding patient-specific medication at the point-of-care.Therapeutic proteins may be subjected to several freeze-thaw cycles throughout manufacturing and storage. The protein solution composition and the freezing conditions may lead to incomplete ice crystallization in the frozen state. This can also result in freeze-concentrate heterogeneity characterized by multiple glass transition temperatures and protein destabilization. The overall objective was to investigate the potential advantages of including a crystallizing excipient (mannitol) along with a sugar (sucrose or trehalose) for frozen storage. This study showed that the addition of mannitol, a readily crystallizing excipient, facilitated ice crystallization. Inclusion of an isothermal hold during cooling (annealing) maximized the mannitol crystallization and resulted in a homogenous freeze-concentrate of a constant composition characterized by a single glass transition temperature. The role of freezing rate and annealing on both mannitol and ice crystallization were discerned using high intensity synchrotron radiation. The addition of sucrose or trehalose, at an appropriate concentration, stabilized the protein. The mannitol to sugar ratio (31 or 11, 5 % w/v) was optimized to selectively cause maximal crystallization of mannitol while retaining the sugar amorphous. Human serum albumin (1 mg/mL) in these optimized and annealed compositions did not show any meaningful aggregation, even after multiple freeze-thaw cycles. Thus, in addition to a sugar as a stabilizer, the use of a crystallizing excipient coupled with an annealing step can provide an avenue for frozen storage of proteins.The objective of the investigation was to determine the ocular biodistribution of cysteamine, a reducing agent used for treatment of cystine crystals in cystinosis, following topical administration of a sustained release formulation and traditional eyedrop formulation. To the right eye only, rabbits received a 50 µL drop of 0.44% cysteamine eyedrops at one drop per waking hour for 2, 6, 12, and 24 h. A second group received one 100 µL drop of a sustained release formulation containing encapsulated cysteamine microspheres suspended in a thermoresponsive gel. Upon serial sacrifice, ocular tissues from both eyes and plasma were obtained and quantified for cysteamine using LC-MS/MS. Cysteamine was detected in the cornea, aqueous humor and vitreous humor. Systemic plasma concentrations of cysteamine from treatment groups were below the limit of detection. As expected, 0.44% cysteamine eyedrops when administered hourly maintained drug concentrations within the cornea at a magnitude 5 times higher than a single dose of the sustained release formulation over 12 h. The sustained release formulation maintained cysteamine presentation across 12 h from a single drop. These studies demonstrate distribution of cysteamine to the eye following topical administration, including high drug uptake to the cornea and low systemic distribution.The integration of mechanistic modeling and machine learning facilitates the understanding and engineering of drug release from controlled release systems. Here, we present hybrid models to predict the effect of drug loading on levonorgestrel release from spray-dried poly(L-lactic acid) microparticles. We developed three Monte Carlo methods that differ in the consideration of polymer's degradability and crystallinity, to simulate drug release from the matrices using the Python programming language. To build each method, we utilized data from the characterization of the particles, such as the actual drug content (ranges from 6% to 52%), size (Dv(50) ∼ 5 μm), and polymer crystallinity (ranges from 0% to 15%). We trained each method using drug release data from particles of 4 batches and derived appropriate machine learning models through regression analysis. Results indicate the contribution of drug diffusion and polymer degradation to drug release for particles of lower drug content ( less then 20 %w/w). At higher drug loadings, particles encountered a combination of burst and diffusional release. We validated the predictive powers of the machine learning models by testing them against experimental data. This paper specifically highlights the power of hybrid modeling to engineer drug release for long-term contraception.Tumorectomy followed by radiotherapy, hormone, and chemotherapy, are the current mainstays for breast cancer treatment. However, these strategies have systemic toxicities and limited treatment outcomes. Hence, there is a crucial need for a novel controlled release delivery system for implantation following tumor resection to effectively prevent recurrence. Here, we fabricated polycaprolactone (PCL)-based electrospun nanofibers containing piperine (PIP), known for chemopreventive and anticancer activities, and also evaluated the impact of collagen (Coll) incorporation into the matrices. In addition to physicochemical characterization such as morphology, hydrophilicity, drug content, release properties, and mechanical behaviors, fabricated nanofibers were investigated in terms of cytotoxicity and involved mechanisms in MCF-7 and 4T1 breast tumor cell lines. In vivo antitumor study was performed in 4T1 tumor-bearing mice. PIP-PCL75-Coll25 nanofiber was chosen as the optimum formulation due to sustained PIP release, good mechanical performance, and superior cytotoxicity. Demonstrating no organ toxicity, animal studies confirmed the superiority of locally administered PIP-PCL75-Coll25 nanofiber in terms of inhibition of growth tumor, induction of apoptosis, and reduction of cell proliferation compared to PIP suspension, blank nanofiber, and the control. Taken together, we concluded that PIP-loaded nanofibers can be introduced as a promising treatment for implantation upon breast tumorectomy.Proliferative verrucous leukoplakia (PVL) is a rapidly progressing, easily relapsed, and cancer-prone oral potential malignant disease (OPMD), for which treatment options are currently limited. Non-invasive photodynamic therapy (PDT) uses specific wavelengths of light to excite photosensitizers and generate reactive oxygen species to induce cytotoxic effects, and it is selective for malignant tissues. However, the lesions of PVL often show hyperkeratosis, which limits the penetration of photosensitizers into the tissue and affects the effectiveness of PDT. Laser, a safe and efficient treatment, has shown great advantages in aiding photosensitizer delivery, due to its ability to accelerate the penetration of 5-aminolevulinic acid (5-ALA) and improve the accumulation of protoporphyrin IX (PPIX) in tissues. In the case report, we achieved complete remission and no recurrence at 8 months in a patient with PVL through laser-assisted PDT, which obtained satisfactory clinical effect and well protected the appearance and function of oral cavity.

The aim of this systematic review was to critically analyze and summarize the currently available scientific evidence concerning antifungal efficacy of aPDT against Candida on acrylic surface.

The focused question was '"Is aPDT effective in minimizing the counts of Candida on acrylic dentures". A literature search was conducted interpedently on the following electronic research databases PubMED/MEDLINE, Cochrane, Google Scholar and Embase. The MeSH terms used were ((antimicrobial photodynamic therapy) OR (light) OR (laser) OR (photodynamic)) AND ((Candida) OR (denture stomatitis)) AND ((denture) OR (acrylic) OR (polymethylmethacrylate) OR (dental prosthesis)). Data was extracted from the studies and quality assessment was carried out using a modified version of the CONSORT checklist.

Eighteen in-vitro anti-microbial studies and 5 clinical studies were included. Twenty-two studies suggested that aPDT was effective in reducing the Candida count on acrylic dentures and one study did not have a significant effect.