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Andrology Nov 2020The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed... (Review)
Review
BACKGROUND
The aim of testosterone replacement therapy (TRT) is to improve symptoms and signs of testosterone deficiency including decreased libido, erectile dysfunction, depressed mood, anaemia, loss of muscle and bone mass, by increasing serum testosterone levels to physiologic range. TRT has been used in the last 70 years, and overtime, numerous preparations and formulations have been developed to improve pharmacokinetics (PKs) and patient compliance. The routes of delivery approved for use in the Western world include buccal, nasal, subdermal, transdermal and intramuscular (IM).
OBJECTIVES
The aim of this narrative review was to describe and compare all available and approved testosterone preparations according to pharmacology, PKs and adverse effects.
MATERIALS AND METHODS
We have performed an extensive PubMed review of the literature on TRT in clinical practice. Contraindications and monitoring of TRT were analyzed by comparing available guidelines released in the last five years. We provide a review of advantages and disadvantages of different modalities of TRT and how to monitor treatment to minimize the risks.
RESULTS
TRT is associated with multiple benefits highly relevant to the patient. However, the recommendations given in different guidelines on TRT are based on data from a limited number of randomized controlled trials (RCTs), as well as non-randomized clinical studies and observational studies. This is the case for the safety of a long-term TRT in late-onset hypogonadism (LOH). No evidence is provided indeed on the effects of TRT on endpoints such as deterioration of heart failure suggesting a cautious approach to T replacement in older men with a history of heart failure.
CONCLUSION
Clinicians must consider the unique characteristics of each patient and make the necessary adjustments in the management of LOH in order to provide the safest and most beneficial results.
Topics: Clinical Decision-Making; Dosage Forms; Drug Administration Routes; Drug Compounding; Eunuchism; Hormone Replacement Therapy; Humans; Male; Risk Assessment; Risk Factors; Testosterone; Treatment Outcome
PubMed: 32068334
DOI: 10.1111/andr.12774 -
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 -
International Journal of Molecular... Jul 2020Irinotecan has been used in the treatment of various malignancies for many years. Still, the knowledge regarding this drug is expanding. The pharmacogenetics of the drug... (Review)
Review
Irinotecan has been used in the treatment of various malignancies for many years. Still, the knowledge regarding this drug is expanding. The pharmacogenetics of the drug is the crucial component of response to irinotecan. Furthermore, new formulations of the drug are introduced in order to better deliver the drug and avoid potentially life-threatening side effects. Here, we give a comprehensive overview on irinotecan's molecular mode of action, metabolism, pharmacogenetics, and toxicity. Moreover, this article features clinically used combinations of the drug with other anticancer agents and introduces novel formulations of drugs (e.g., liposomal formulations, dendrimers, and nanoparticles). It also outlines crucial mechanisms of tumor cells' resistance to the active metabolite, ethyl-10-hydroxy-camptothecin (SN-38). We are sure that the article will constitute an important source of information for both new researchers in the field of irinotecan chemotherapy and professionals or clinicians who are interested in the topic.
Topics: Activation, Metabolic; Antineoplastic Combined Chemotherapy Protocols; DNA, Neoplasm; Dosage Forms; Drug Compounding; Drug Resistance, Neoplasm; Drug Synergism; Female; Humans; Irinotecan; Male; Models, Molecular; Molecular Structure; Neoplasm Proteins; Neoplasms; Nucleic Acid Conformation; Polymorphism, Single Nucleotide; Prodrugs; Protein Conformation; Topoisomerase I Inhibitors
PubMed: 32664667
DOI: 10.3390/ijms21144919 -
JAMA Apr 2023
Topics: Cannabidiol; Cannabis; Melatonin; Administration, Oral; United States; Dosage Forms
PubMed: 37097362
DOI: 10.1001/jama.2023.2296 -
Macromolecular Rapid Communications Apr 2022Hydrogels belong to the most promising materials in polymer and materials science at the moment. As they feature soft and tissue-like character as well as high... (Review)
Review
Hydrogels belong to the most promising materials in polymer and materials science at the moment. As they feature soft and tissue-like character as well as high water-content, a broad range of applications are addressed with hydrogels, e.g., tissue engineering and wound dressings but also soft robotics, drug delivery, actuators, and catalysis. Ways to tailor hydrogel properties are crosslinking mechanisms, hydrogel shape, and reinforcement, but new features can be introduced by variation of hydrogel composition as well, e.g., via monomer choice, functionalization or compartmentalization. In particular, multicompartment hydrogels drive progress toward complex and highly functional soft materials. In the present review the latest developments in multicompartment hydrogels are highlighted with a focus on three types of compartments; micellar/vesicular, droplets, and multilayers including various subcategories. Furthermore, several morphologies of compartmentalized hydrogels and applications of multicompartment hydrogels will be discussed as well. Finally, an outlook toward future developments of the field will be given. The further development of multicompartment hydrogels is highly relevant for a broad range of applications and will have a significant impact on biomedicine and organic devices.
Topics: Drug Delivery Systems; Hydrogels; Micelles; Polymers; Tissue Engineering
PubMed: 35092101
DOI: 10.1002/marc.202100895 -
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 -
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 -
Biomolecules Aug 2021The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness,... (Review)
Review
The eye is at the forefront of developing therapies for genetic diseases. With the FDA approval of the first gene-therapy drug for a form of congenital blindness, numerous studies have been initiated to develop gene therapies for other forms of eye diseases. These examinations have revealed new information about the benefits as well as restrictions to using drug-delivery routes to the different parts of the eye. In this article, we will discuss a brief history of gene therapy and its importance to the eye and ocular delivery landscape that is currently being investigated, and provide insights into their advantages and disadvantages. Efficient delivery routes and vehicle are crucial for an effective, safe, and longer-lasting therapy.
Topics: Animals; Choroidal Effusions; DNA; Eye; Eye Diseases; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans; Intravitreal Injections; Liposomes; Nanoparticles; Peptides; Subretinal Fluid; Viruses; Vitreous Body
PubMed: 34439800
DOI: 10.3390/biom11081135