Furthermore, the review investigates how a 3DP nasal cast can aid in the development of nose-to-brain drug delivery systems, while also exploring the potential of bioprinting for nerve regeneration and the practical applications of 3D-printed drugs, including polypills, in treating neurological ailments.
Within the gastrointestinal tract of rodents, oral administration of spray-dried amorphous solid dispersions containing new chemical entities and the pH-dependent soluble polymer hydroxypropyl methylcellulose acetate succinate (HPMC-AS) led to the formation of solid agglomerates. Animal welfare is potentially jeopardized by these agglomerates, which comprise intra-gastrointestinal aggregated oral dosage forms known as pharmacobezoars. see more An earlier study presented an in vitro model for evaluating the potential for aggregation in amorphous solid dispersions made from suspensions, as well as methods for diminishing this aggregation. We explored the potential of viscosity enhancement in the vehicle used for in vitro amorphous solid dispersion suspensions to mitigate the risk of pharmacobezoar development in rats following repeated daily oral dosing. The 2400 mg/kg/day dose, employed in the main study, was identified through a preliminary dose-ranging study. In the course of the dose-finding study, MRI examinations were undertaken at closely spaced intervals to elucidate the process of pharmacobezoar formation. MRI scans illustrated the forestomach's participation in the creation of pharmacobezoars, and solutions with improved viscosity lessened the incidence of pharmacobezoars, postponed their formation, and reduced the overall quantity of pharmacobezoars found during post-mortem examination.
Japan's drug packaging landscape is significantly dominated by press-through packaging (PTP), an approach underpinned by a proven and economical manufacturing protocol. Nevertheless, unsolved problems and developing safety needs for users in diverse age categories remain to be explored. Accident reports concerning children and the elderly highlight the need for an assessment of the safety and quality of PTP and emerging forms, including child-resistant and senior-friendly (CRSF) packaging. We carried out a study focusing on the ergonomic differences between commonly utilized and newly developed Personal Protective Technologies (PTPs) for children and older adults. The opening tests involved children and older adults using a widespread PTP type (Type A), and child-resistant PTPs (Types B1 and B2), which were constructed from soft aluminum foil. see more Older patients with rheumatoid arthritis (RA) underwent the same initial test. Children struggled with opening the CR PTP, with a success rate of only one child among eighteen in opening the Type B1. In contrast, all eight elderly participants successfully opened Type B1, and eight patients with rheumatoid arthritis effortlessly managed to open both types, B1 and B2. New materials hold the key to elevating the quality of CRSF PTP, according to these findings.
Synthesis and evaluation of lignohydroquinone conjugates (L-HQs), using a hybridization strategy, were performed, and the compounds were examined for their cytotoxic effect on several cancer cell lines. see more Naturally occurring podophyllotoxin and chemically altered terpenylnaphthohydroquinones, which were formed by the modification of natural terpenoids, were used to produce the L-HQs. Aliphatic or aromatic linkers connected the conjugate's constituent entities. The L-HQ hybrid, boasting an aromatic spacer, demonstrated a dual in vitro cytotoxic effect within the evaluated group, rooted in the individual activities of its parent molecules. This hybrid retained its selectivity and exhibited strong cytotoxicity against colorectal cancer cells, evident at both 24-hour and 72-hour incubation times, yielding IC50 values of 412 nM and 450 nM, respectively. The cell cycle blockade, a finding from flow cytometry, molecular dynamics, and tubulin interaction studies, signifies the utility of these hybrid molecules. These hybrids, while sizable, still effectively docked into the colchicine-binding site of tubulin. These findings validate the hybridization strategy, motivating further research into non-lactonic cyclolignans.
The complex composition of different cancers makes anticancer drugs used in monotherapy ineffective against a wide array of them. Additionally, the anticancer medications presently accessible present numerous hurdles, including drug resistance, the unresponsiveness of cancerous cells to treatment, adverse effects on the patient, and inconveniences faced by patients. Therefore, phytochemicals of plant origin could potentially be a superior replacement for conventional chemotherapy in cancer treatment, exhibiting several benefits such as reduced side effects, synergistic action through multiple pathways, and affordability. Additionally, the poor solubility in water and limited bioavailability of phytochemicals present significant hurdles in achieving effective anticancer outcomes, necessitating strategies to improve absorption and efficacy. Therefore, employing nanotechnology-driven novel carriers, phytochemicals and conventional anticancer drugs are delivered together to achieve improved cancer treatment. Nanoemulsions, nanosuspensions, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, polymeric micelles, dendrimers, metallic nanoparticles, and carbon nanotubes, novel drug carriers, provide multiple advantages including increased solubility, decreased adverse effects, improved efficacy, minimized dosage, improved dosing frequency, reduced drug resistance, enhanced bioavailability, and improved patient compliance. This review compiles a variety of phytochemicals used in cancer treatment, examining combined phytochemical and anticancer drug therapies, along with diverse nanotechnology-based delivery systems for these combined therapies in treating cancer.
Cancer immunotherapy necessitates the activation of T cells, which play significant roles in diverse immune reactions. Earlier research showed that various immune cells, including T cells and their subsets, actively internalized polyamidoamine (PAMAM) dendrimers modified with 12-cyclohexanedicarboxylic acid (CHex) and phenylalanine (Phe). A study was conducted to synthesize carboxy-terminal dendrimers with a range of Phe attachments. The investigation aimed to determine the association of these dendrimers with T cells and how the density of terminal Phe impacts this association. The presence of Phe substitutions at more than 50% of carboxy-terminal dendrimer termini resulted in improved binding to T cells and other immune cells. The highest degree of association between carboxy-terminal phenylalanine-modified dendrimers (at a density of 75%) and T cells, along with other immune cells, was observed. This association was linked to their interaction with liposomes. Protoporphyrin IX (PpIX), a model drug, was encapsulated within carboxy-terminal Phe-modified dendrimers, which were subsequently employed for the delivery of the drug to T cells. Our research results show that carboxy-terminal phenylalanine-modified dendrimers are suitable for the transport of materials to T cells.
Due to the extensive availability and affordability of 99Mo/99mTc generators internationally, the creation and use of new 99mTc-labeled radiopharmaceuticals are sustained. Developments in preclinical and clinical approaches to managing neuroendocrine neoplasms patients have, in recent years, prominently featured somatostatin receptor subtype 2 (SST2) antagonists. This preference stems from their superior tumor targeting and heightened diagnostic accuracy compared to agonists directed at the SST2 receptor. The production of a 99mTc-labeled SST2 antagonist, [99mTc]Tc-TECANT-1, using a reliable and facile method, specifically tailored to hospital radiopharmacy settings, was targeted to enable a multi-center clinical trial. For successful and reproducible on-site preparation, a freeze-dried kit containing three vials was developed for human use shortly before administration of the radiopharmaceutical. During the optimization procedure, the final kit composition was established in line with radiolabeling results, which analyzed parameters including precursor content, pH, and buffer solutions, alongside different kit formulations. The GMP-grade batches, after preparation, were found to meet all previously defined specifications, including the sustained stability of the kit and the [99mTc]Tc-TECANT-1 product itself over the long term [9]. In addition, the chosen precursor material adheres to micro-dosing principles, as substantiated by an extended single-dose toxicity study. This study determined a no-observed-adverse-effect level (NOEL) of 5 mg/kg body weight (BW). This is over 1000 times greater than the planned human dose of 20 g. Finally, the evidence supports [99mTc]Tc-TECANT-1's advancement to a pioneering first-in-human clinical trial.
The use of live microorganisms, specifically probiotics, is a noteworthy area of interest in its contribution to patient well-being. Only by preserving the microbial viability throughout the dosage form's lifespan can effective administration be guaranteed. Storage stability can be increased by the drying method, and the tablet's straightforward administration, along with its positive impact on patient compliance, makes it an attractive final solid dosage form. This study investigates the drying of Saccharomyces cerevisiae yeast through a fluidized bed spray granulation process, since the probiotic Saccharomyces boulardii is a subspecies. Microorganism preservation relies heavily on two primary methods: spray drying and lyophilization. Fluidized bed granulation, in comparison, offers faster drying and lower temperatures than either of these. The carrier particles of excipients, dicalcium phosphate (DCP), lactose (LAC), and microcrystalline cellulose (MCC), were subjected to a spray application of yeast cell suspensions, which were supplemented with protective additives. To evaluate their protective capabilities, mono-, di-, oligo-, and polysaccharides, skimmed milk powder, and an alditol were tested; these substances, or their chemically analogous counterparts, are recognized in other drying procedures for their ability to stabilize biological structures, such as cell membranes, thus enhancing survival during dehydration.