-
Signal Transduction and Targeted Therapy Dec 2021Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to... (Review)
Review
Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell-hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.
Topics: Drug Carriers; Humans; Hydrogels
PubMed: 34916490
DOI: 10.1038/s41392-021-00830-x -
Molecules (Basel, Switzerland) Sep 2021The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems... (Review)
Review
The drug delivery system enables the release of the active pharmaceutical ingredient to achieve a desired therapeutic response. Conventional drug delivery systems (tablets, capsules, syrups, ointments, etc.) suffer from poor bioavailability and fluctuations in plasma drug level and are unable to achieve sustained release. Without an efficient delivery mechanism, the whole therapeutic process can be rendered useless. Moreover, the drug has to be delivered at a specified controlled rate and at the target site as precisely as possible to achieve maximum efficacy and safety. Controlled drug delivery systems are developed to combat the problems associated with conventional drug delivery. There has been a tremendous evolution in controlled drug delivery systems from the past two decades ranging from macro scale and nano scale to intelligent targeted delivery. The initial part of this review provides a basic understanding of drug delivery systems with an emphasis on the pharmacokinetics of the drug. It also discusses the conventional drug delivery systems and their limitations. Further, controlled drug delivery systems are discussed in detail with the design considerations, classifications and drawings. In addition, nano-drug delivery, targeted and smart drug delivery using stimuli-responsive and intelligent biomaterials is discussed with recent key findings. The paper concludes with the challenges faced and future directions in controlled drug delivery.
Topics: Animals; Biocompatible Materials; Drug Carriers; Drug Delivery Systems; Humans; Nanoparticles; Pharmaceutical Preparations
PubMed: 34641447
DOI: 10.3390/molecules26195905 -
Nutrients Jul 2019Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed...
Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.
Topics: Adolescent; Adult; Biological Availability; Dietary Supplements; Dosage Forms; Drug Liberation; Female; Humans; Magnesium; Male; Young Adult
PubMed: 31330811
DOI: 10.3390/nu11071663 -
JAMA Apr 2023
Topics: Cannabidiol; Cannabis; Melatonin; Administration, Oral; United States; Dosage Forms
PubMed: 37097362
DOI: 10.1001/jama.2023.2296 -
Journal of Controlled Release :... Apr 2021Polymeric micelles, i.e. aggregation colloids formed in solution by self-assembling of amphiphilic polymers, represent an innovative tool to overcome several issues... (Review)
Review
Polymeric micelles, i.e. aggregation colloids formed in solution by self-assembling of amphiphilic polymers, represent an innovative tool to overcome several issues related to drug administration, from the low water-solubility to the poor drug permeability across biological barriers. With respect to other nanocarriers, polymeric micelles generally display smaller size, easier preparation and sterilization processes, and good solubilization properties, unfortunately associated with a lower stability in biological fluids and a more complicated characterization. Particularly challenging is the study of their interaction with the biological environment, essential to predict the real in vivo behavior after administration. In this review, after a general presentation on micelles features and properties, different characterization techniques are discussed, from the ones used for the determination of micelles basic characteristics (critical micellar concentration, size, surface charge, morphology) to the more complex approaches used to figure out micelles kinetic stability, drug release and behavior in the presence of biological substrates (fluids, cells and tissues). The techniques presented (such as dynamic light scattering, AFM, cryo-TEM, X-ray scattering, FRET, symmetrical flow field-flow fractionation (AF4) and density ultracentrifugation), each one with their own advantages and limitations, can be combined to achieve a deeper comprehension of polymeric micelles in vivo behavior. The set-up and validation of adequate methods for micelles description represent the essential starting point for their development and clinical success.
Topics: Colloids; Drug Carriers; Drug Delivery Systems; Micelles; Polymers; Solubility
PubMed: 33652113
DOI: 10.1016/j.jconrel.2021.02.031 -
Pharmaceutical Research May 2017
Topics: Chemistry, Pharmaceutical; Dosage Forms; Drug Compounding; Drug Liberation; Excipients; Humans; Pharmaceutical Preparations; Solubility
PubMed: 28299534
DOI: 10.1007/s11095-017-2137-z -
BioMed Research International 2020Oleanolic acid is a pentacyclic triterpenoid compound that exists widely in medicinal herbs and other plants. Because of the extensive pharmacological activity,... (Review)
Review
Oleanolic acid is a pentacyclic triterpenoid compound that exists widely in medicinal herbs and other plants. Because of the extensive pharmacological activity, oleanolic acid has attracted more and more attention. However, the structural characteristics of oleanolic acid prevent it from being directly made into new drugs, which limits the application of oleanolic acid. Through the application of modern preparation techniques and methods, different oleanolic acid dosage forms and derivatives have been designed and synthesized. These techniques can improve the water solubility and bioavailability of oleanolic acid and lay a foundation for the new drug development. In this review, the recent progress in understanding the oleanolic acid dosage forms and its derivatives are discussed. Furthermore, these products were evaluated comprehensively from the perspective of characterization and pharmacokinetics, and this work may provide ideas and references for the development of oleanolic acid preparations.
Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cyclodextrins; Dosage Forms; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Inhibitory Concentration 50; Liposomes; Liver; Mice; Micelles; Nanoparticles; Oleanolic Acid; Phospholipids; Plants; Solubility; Structure-Activity Relationship
PubMed: 33299854
DOI: 10.1155/2020/1308749 -
International Journal of Molecular... Dec 2019Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage...
Safe and effective delivery of therapeutics at the target site is the key to successful therapy. Nanocarriers can offer significant advantages over conventional dosage forms. Over the decades, nanoparticles have been extensively used to increase bioavailability, improve solubility and stability, reduce toxicities, and facilitate the controlled release of therapeutics. Further, nanoparticles have often been surface-functionalized with a variety of ligands to enhance circulation half-life and increase target-specificity. Although nanotechnology has shown significant therapeutic benefits for multiple biomedical applications, limited nanoparticle-based formulations have progressed to clinical trials, and only a few have reached the pharmaceutical market. This editorial is an introduction to the special issue entitled Surface-Functionalized Nanoparticles as Drug Carriers. We outline the scope of the special issue, summarize the results and conclusions of the nine articles published in this issue, and provide perspective on the application of surface-functionalized nanoparticles in the drug delivery field.
Topics: Biological Availability; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Delivery Systems; Drug Liberation; Humans; Nanoparticles; Nanotechnology
PubMed: 31861113
DOI: 10.3390/ijms20246352 -
International Journal of Pharmaceutics Mar 2022The total number of paediatric formulations available only account for a small proportion of the full therapeutic plethora required to effectively treat paediatrics and,... (Review)
Review
The total number of paediatric formulations available only account for a small proportion of the full therapeutic plethora required to effectively treat paediatrics and, therefore, the availability of high quality medicines designed specifically for children remains an ongoing challenge. Currently, the World Health Organisation (WHO) report that around 50% of medication issued for long-term conditions are not taken as advised, whilst it has also been established that, in general practice, around one tenth of medicines prescribed for children are either off-label or unlicensed. Such off-label and unlicensed use is owing to the considerable anatomical and physiological differences observed between paediatric subsets. Identifying such differences, is essential for better informing paediatric drug development and assisting regulatory reviews, whilst ensuring safe and effective therapeutic concentrations of pharmacological substances. Points covered: The review discusses factors affecting the safety, toxicity and efficacy of paediatric drug delivery systems. The research highlights features of the gastrointestinal tract and reports anatomical and physiological differences between paediatrics and adults. Additionally, differences observed in paediatric pharmacokinetic profiles (absorption, distribution, metabolism and elimination) due to physiological differences are also discussed. Furthermore, this review considers the advantages and limitations of current paediatric specific dosage forms available and assesses the acceptability of innovative small flexible solid oral dosage forms. Lastly, this review highlights factors affecting paediatric medicine adherence and acceptability and discusses the techniques available to overcome barriers associated with non-adherence.
Topics: Adult; Child; Dosage Forms; Humans; Off-Label Use; Pediatrics; Pharmaceutical Preparations
PubMed: 35092832
DOI: 10.1016/j.ijpharm.2022.121501 -
International Journal of Pharmaceutics Jun 2021Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug... (Review)
Review
Nanosizing of pharmaceutical drug particles is one of the most important drug delivery platforms approaches for the commercial development of poorly water-soluble drug molecules. Though nanosizing of drug particles has been proven to greatly enhance drugs dissolution rate and apparent solubility, nanosized materials have presented significant challenges for their formulation as solid dosage forms (e.g. tablets, capsules). This is due to the strong Van der Waals attraction forces between dry nanoparticles leading to aggregation, cohesion, and consequently poor flowability. In this review, the broad area of nanomedicines is overviewed with the primary focus on drug nanocrystals and the top-down and bottom-up methods used in their fabrication. The review also looks at how nanosuspensions of pharmaceutical drugs are generated and stabilised, followed by subsequent strategies for isolation of the nanoparticles. A perspective on the future outlook for drug nanocrystals is also presented.
Topics: Chemistry, Pharmaceutical; Drug Delivery Systems; Nanoparticles; Pharmaceutical Preparations; Solubility; Tablets; Technology, Pharmaceutical
PubMed: 33992712
DOI: 10.1016/j.ijpharm.2021.120708