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Journal of Materials Chemistry. B Dec 2023Luteolin (Lu) is a naturally occurring flavonoid compound with a diverse array of pharmacological activities, including anti-tumor, anti-inflammatory, antibacterial, and... (Review)
Review
Luteolin (Lu) is a naturally occurring flavonoid compound with a diverse array of pharmacological activities, including anti-tumor, anti-inflammatory, antibacterial, and neuroprotective properties. However, the therapeutic efficacy and clinical application of Lu are significantly hindered by inherent limitations, such as poor water solubility, short half-life, low bioavailability, and potential off-target toxicity. Recent studies have demonstrated that the utilization of nanocarriers presents a promising strategy to enhance the solubility of Lu, prolong its circulation time, and improve its targeting ability. Despite numerous reviews over the past few decades having focused on the source, pharmacological activities, and molecular mechanisms of Lu, there exists a conspicuous gap in the literature regarding a comprehensive review of Lu-loaded nanoformulations and their applications. To address this gap, we present an exhaustive overview of the advancements and applications of nano-scale drug delivery systems specifically designed for Lu. These platforms encompass micelles, nanocarrier-based systems, emulsified drug delivery systems, and vesicular drug delivery systems. We provide detailed insights into the synthetic materials, preparation methods, physicochemical properties, and significant outcomes associated with these nanoformulations. This systematic review will be particularly valuable to researchers seeking novel avenues in the field of nano-delivery strategies and exploring the potential clinical applications of Lu.
Topics: Luteolin; Nanoparticle Drug Delivery System; Nanoparticles; Drug Delivery Systems; Micelles
PubMed: 37986608
DOI: 10.1039/d3tb01753b -
Acta Pharmaceutica (Zagreb, Croatia) Jun 2024Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring... (Review)
Review
Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.
Topics: Printing, Three-Dimensional; Humans; Administration, Oral; Child; Tablets; Drug Compounding; Technology, Pharmaceutical; Precision Medicine; Dosage Forms; Chemistry, Pharmaceutical; Pharmaceutical Preparations
PubMed: 38815205
DOI: 10.2478/acph-2024-0012 -
International Journal of Pharmaceutics Nov 2023The aim of this work was to develop fast disintegrating dosage forms, including fast disintegrating tablets (FDTs) and films (FDFs), for oral insulin delivery...
The aim of this work was to develop fast disintegrating dosage forms, including fast disintegrating tablets (FDTs) and films (FDFs), for oral insulin delivery incorporating mucoadhesive thiolated chitosan (TCS)-based nanoparticles (NPs). Cyclodextrin (CD)-insulin complexes were formed to prevent insulin from degradation and further optimally prepared NPs in order to improve the mucoadhesive properties. After that, these NPs were incorporated into the dosage forms and then evaluated for their morphology as well as physical and mechanical properties. The disintegration time, insulin content, mucoadhesive properties, insulin release, cytotoxicity, in vivo hypoglycemic effect, and stability of dosage forms were studied. Results showed that the CD-insulin complexes were successfully encapsulated into the mucoadhesive NPs. The 15 %w/w CD-insulin complex-loaded NPs, which were probably dispersed and/or fused into the dosage forms, showed promising characteristics, including rapid disintegration as well as good physical and mechanical properties to withstand erosion during handling and storage. The porous structure of the FDTs promoted liquid flow and induced rapid disintegration. The dosage forms provided buccal mucoadhesion before, during, and/or after the disintegration. The FDFs containing hydroxypropyl β-cyclodextrin (HPβCD)-insulin complex-loaded NPs increased mucoadhesion, increasing insulin release. Furthermore, these dosage forms provided excellent in vivo hypoglycemic response with a prolonged effect in diabetic mice and had no cytotoxicity toward the gingival fibroblast cells. In addition, they were stable at temperatures between 2 and 8 °C for three months. The results indicate that these formulations could be applied as promising dosage forms for use in oral insulin delivery.
Topics: Mice; Animals; Insulin; Diabetes Mellitus, Experimental; Tablets; Hypoglycemic Agents; Nanoparticles; Chitosan; Drug Delivery Systems
PubMed: 37839494
DOI: 10.1016/j.ijpharm.2023.123513 -
Respiratory Medicine 2023Dry powder inhalers (DPIs) are essential in treating patients with pulmonary diseases. Since DPIs were introduced in the 1960s, a remarkable improvement has been made in... (Review)
Review
Dry powder inhalers (DPIs) are essential in treating patients with pulmonary diseases. Since DPIs were introduced in the 1960s, a remarkable improvement has been made in their technology, dose delivery, efficiency, reproducibility, stability, and performance based on safety and efficacy. While there are many DPIs on the market and several more under development, it is vital to evaluate the performance of DPIs for effective aerosol drug delivery to patients with respiratory disorders. Their performance evaluation includes the physicochemical properties of the drug powder formulation, metering system, device design, dose preparation, inhalation technique, and patient-device integration. The purpose of this paper is to review current literature evaluating DPIs through in vitro studies, computational fluid models, and in vivo/clinical studies. We will also explain how mobile health applications are used to monitor and evaluate patients' adherence to prescribed medications.
Topics: Humans; Dry Powder Inhalers; Reproducibility of Results; Aerosols; Drug Delivery Systems; Powders; Technology; Administration, Inhalation
PubMed: 37244487
DOI: 10.1016/j.rmed.2023.107281 -
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 -
Macromolecular Bioscience Jul 2023Numerous factors, such as degeneration and accidents, frequently cause cartilage deterioration. Owing to the absence of blood vessels and nerves in cartilage tissue, the... (Review)
Review
Numerous factors, such as degeneration and accidents, frequently cause cartilage deterioration. Owing to the absence of blood vessels and nerves in cartilage tissue, the ability of cartilage tissue to heal itself after an injury is relatively low. Hydrogels are beneficial for cartilage tissue engineering owing to their cartilage-like structure and advantageous properties. Due to the disruption of its mechanical structure, the bearing capacity and shock absorption of cartilage are diminished. The tissue should possess excellent mechanical properties to ensure the efficacy of cartilage tissue repair. This paper discusses the application of hydrogels in the fields of cartilage repair, the mechanical properties of hydrogels used for cartilage repair, and the materials used for hydrogels in cartilage tissue engineering. In addition, the challenges faced by hydrogels and future research directions are discussed.
Topics: Hydrogels; Cartilage; Tissue Engineering; Cartilage, Articular
PubMed: 36802277
DOI: 10.1002/mabi.202200539 -
Molecular Pharmaceutics Sep 2023Optimization of the in vivo performance of dosage forms in humans is essential in developing not only conventional formulations but also drug delivery system (DDS)... (Review)
Review
Optimization of the in vivo performance of dosage forms in humans is essential in developing not only conventional formulations but also drug delivery system (DDS) formulations. Although animal experiments are still useful for these formulations, in silico approaches have become increasingly important for DDS formulations with regard to species-specific differences in physiology that can affect the in vivo performance of dosage forms between animals and humans. Furthermore, it is also important to couple in vitro characterizations with in silico models to predict in vivo performance in humans precisely. In this review article, I summarized in vitro-in silico approaches to predicting the in vivo performance of oral DDS formulations (amorphous solid dispersions, lipid-based formulations, nanosized formulations, cyclodextrins-based formulations, sustained release products, enteric coat products, and orally disintegrating tablets) and parenteral DDS formulations (cyclodextrins-based formulations, liposomes, and inhaled formulations).
Topics: Animals; Humans; Administration, Oral; Chemistry, Pharmaceutical; Solubility; Drug Delivery Systems; Computer Simulation; Tablets; Cyclodextrins
PubMed: 37523273
DOI: 10.1021/acs.molpharmaceut.3c00184 -
Biomaterials Aug 2023Oral protein vaccines are mainly used to prevent the infection of intestinal pathogens in clinic due to their high safety and strong compliance. However, it is necessary...
Oral protein vaccines are mainly used to prevent the infection of intestinal pathogens in clinic due to their high safety and strong compliance. However, it is necessary to design the efficient delivery systems to overcome the harsh gastrointestinal environment in the application process. Here we established a programmable oral bacterial hydrogel system for spatiotemporally controllable production and release of nanovaccines. The system was divided into three parts: (1) Engineered bacteria were encapsulated in chitosan-sodium alginate microcapsules, which offered protection against the extreme acid conditions in the stomach. (2) Microcapsules were dissolved, and then engineered bacteria were released and colonized in the intestine. (3) The release of nanovaccines was controlled periodically by a synchronous lysis genetic circuit for tumor immunotherapy. Compared to control groups, tumor volume of subcutaneous tumor-bearing mice treated with bacterial microgels releasing optimized nanovaccine was almost inhibited by 75% and T cell response was activated at least 2-fold. We believe that this programmable bacterial hydrogel will offer a promising way for the application of oral nanovaccines.
Topics: Mice; Animals; Capsules; Hydrogels; Bacteria; Immunotherapy; Neoplasms; Cancer Vaccines; Nanoparticles
PubMed: 37182418
DOI: 10.1016/j.biomaterials.2023.122147 -
International Journal of Pharmaceutics Jul 2023Quality issues related to compressed oral solid dosage (OSD) forms, such as tablets, arise during the design, development, and production stages, despite established...
Quality issues related to compressed oral solid dosage (OSD) forms, such as tablets, arise during the design, development, and production stages, despite established processes and robust production tools. One of the primary quality concerns is the disintegration properties and drug release profile of immediate-release OSD products, which depend on their micro-texture and micro-viscoelastic properties at the grain level. These properties are influenced by the composition of the formulation, particularly the disintegrant level in the tablet matrix and the porosity of the matrix. In this study, a novel, rapid, non-destructive ultrasonic characterization technique was proposed to correlate the sensitivity of propagating elastic wave speeds, physical/mechanical properties, and the dispersion profile of the OSD material with the disintegrant level (% w/w) in the formulation and the compression force applied during tableting. The proposed characterization framework involves transmitting pressure (longitudinal) and shear (transverse) waves through the OSDs to calculate the speed of sound, which in turn provides information on the apparent Young's and shear moduli. In addition, the attenuation profile of the propagating wave is obtained through dispersion analysis. To investigate the impact of disintegrants and compression force on ultrasonic wave propagation in OSDs, we incorporated seven levels of a frequently used disintegrant. In each formulation, OSDs are compacted in five compaction forces. The sensitivity of wave speeds, physical/mechanical properties, and attenuation profile was observed with each disintegrant and compression force level. The utilization of ultrasonic techniques may present a viable solution for rapid, non-destructive, non-invasive, and cost-effective testing methods required in continuous manufacturing (CM) and real-time release testing (RTRT), and its practical utility in pharmaceutical manufacturing is also discussed.
Topics: Excipients; Tablets; Mechanical Phenomena; Porosity; Pressure
PubMed: 37356509
DOI: 10.1016/j.ijpharm.2023.123171 -
Journal of Pharmaceutical Sciences Jul 2024The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure... (Review)
Review
The production of paediatric pharmaceutical forms represents a unique challenge within the pharmaceutical industry. The primary goal of these formulations is to ensure therapeutic efficacy, safety, and tolerability in paediatric patients, who have specific physiological needs and characteristics. In recent years, there has been a significant increase in attention towards this area, driven by the need to improve drug administration to children and ensure optimal and specific treatments. Technological innovation has played a crucial role in meeting these requirements, opening new frontiers in the design and production of paediatric pharmaceutical forms. In particular, three emerging technologies have garnered considerable interest and attention within the scientific and industrial community: 3D printing, prilling/vibration, and microfluidics. These technologies offer advanced approaches for the design, production, and customization of paediatric pharmaceutical forms, allowing for more precise dosage modulation, improved solubility, and greater drug acceptability. In this review, we delve into these cutting-edge technologies and their impact on the production of paediatric pharmaceutical forms. We analyse their potential, associated challenges, and recent developments, providing a comprehensive overview of the opportunities that these innovative methodologies offer to the pharmaceutical sector. We examine different pharmaceutical forms generated using these techniques, evaluating their advantages and disadvantages.
Topics: Printing, Three-Dimensional; Humans; Child; Microfluidics; Dosage Forms; Technology, Pharmaceutical; Pediatrics; Pharmaceutical Preparations; Drug Compounding; Chemistry, Pharmaceutical; Solubility
PubMed: 38582283
DOI: 10.1016/j.xphs.2024.04.001