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International Journal of Pharmaceutics Mar 2020
Topics: Drug Delivery Systems; Humans; Pharmaceutical Preparations; Solubility
PubMed: 31958490
DOI: 10.1016/j.ijpharm.2020.119055 -
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 -
Chemistry (Weinheim An Der Bergstrasse,... Dec 2022Polymer alternatives sourced from nature have attracted increasing attention for applications in medicine, cosmetics, agriculture, food, water purification, and more.... (Review)
Review
Polymer alternatives sourced from nature have attracted increasing attention for applications in medicine, cosmetics, agriculture, food, water purification, and more. Among them, chitosan is the most versatile due to its full biodegradability, exceptional biocompatibility, multipurpose bioactivity, and low toxicity. Although remarkable progress has been made in its synthetic modification by using C3/C6 secondary/primary hydroxy (-OH) and the C2 amino (-NH ) active sites, its solubility under physiological conditions remains limited and has hampered larger-scale adoption. This review summarizes different synthetic methods that increase chitosan's hydrophilicity and water solubility by using covalent modifications, namely amino acid addition, quaternary ammonium formation, phosphorylation, and carboxymethylation. We also review several applications for each type of substitution in fields such as cosmetics, medicine, agriculture, and water purification, and provide an outlook and perspective for future modifications and implementations.
Topics: Chitosan; Solubility; Hydrophobic and Hydrophilic Interactions
PubMed: 36073726
DOI: 10.1002/chem.202202156 -
Journal of Medicinal Chemistry Sep 2023The oxetane ring is an emergent, underexplored motif in drug discovery that shows attractive properties such as low molecular weight, high polarity, and marked... (Review)
Review
The oxetane ring is an emergent, underexplored motif in drug discovery that shows attractive properties such as low molecular weight, high polarity, and marked three-dimensionality. Oxetanes have garnered further interest as isosteres of carbonyl groups and as molecular tools to fine-tune physicochemical properties of drug compounds such as p, LogD, aqueous solubility, and metabolic clearance. This perspective highlights recent applications of oxetane motifs in drug discovery campaigns (2017-2022), with emphasis on the effect of the oxetane on medicinally relevant properties and on the building blocks used to incorporate the oxetane ring. Based on this analysis, we provide an overview of the potential benefits of appending an oxetane to a drug compound, as well as potential pitfalls, challenges, and future directions.
Topics: Drug Discovery; Ethers, Cyclic; Kinetics; Solubility
PubMed: 37676858
DOI: 10.1021/acs.jmedchem.3c01101 -
Molecules (Basel, Switzerland) Aug 2020Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for... (Review)
Review
Lipid-soluble bioactives are important nutrients in foods. However, their addition in food formulations, is often limited by limited solubility and high tendency for oxidation. Lipid-soluble bioactives, such as vitamins A, E, D and K, carotenoids, polyunsaturated fatty acids (PUFA) and essential oils are generally dispersed in water-based solutions by homogenization. Among the different homogenization technologies available, nanoemulsions are one of the most promising. Accordingly, this review aims to summarize the most recent advances in nanoemulsion technology for the encapsulation of lipid-soluble bioactives. Modern approaches for producing nanoemulsion systems will be discussed. In addition, the challenges on the encapsulation of common food ingredients, including the physical and chemical stability of the nanoemulsion systems, will be also critically examined.
Topics: Algorithms; Drug Compounding; Drug Stability; Emulsions; Lipids; Models, Theoretical; Molecular Structure; Nanoparticles; Nanotechnology; Solubility
PubMed: 32878137
DOI: 10.3390/molecules25173966 -
Biomedicine & Pharmacotherapy =... May 2022Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role... (Review)
Review
Bioactive phytochemicals from natural source have gained tremendous interest over several decades due to their wide and diverse therapeutic activities playing key role as functional food supplements, pharmaceutical and nutraceutical products. Nevertheless, their application as therapeutically active moieties and formulation into novel drug delivery systems are hindered due to major drawbacks such as poor solubility, bioavailability and dissolution rate and instability contributing to reduction in bioactivity. These drawbacks can be effectively overcome by their complexation with different cyclodextrins. Present article discusses complexation of phytochemicals varying from flavonoids, phenolics, triterpenes, and tropolone with different natural and synthetic cyclodextrins. Moreover, the article summarizes complexation methods, complexation efficiency, stability, stability constants and enhancement in rate and extent of dissolution, bioavailability, solubility, in vivo and in vitro activities of reported complexed phytochemicals. Additionally, the article presents update of published patent details comprising of complexed phytochemicals of therapeutic significance. Thus, phytochemical cyclodextrin complexes have tremendous potential for transformation into drug delivery systems as substantiated by significant outcome of research findings.
Topics: Biological Availability; Cyclodextrins; Pharmaceutical Preparations; Phytochemicals; Solubility
PubMed: 35339826
DOI: 10.1016/j.biopha.2022.112862 -
Chemical Reviews Sep 2022Water solubility and structural stability are key merits for proteins defined by the primary sequence and 3D-conformation. Their manipulation represents important... (Review)
Review
Water solubility and structural stability are key merits for proteins defined by the primary sequence and 3D-conformation. Their manipulation represents important aspects of the protein design field that relies on the accurate placement of amino acids and molecular interactions, guided by underlying physiochemical principles. Emulated designer proteins with well-defined properties both fuel the knowledge-base for more precise computational design models and are used in various biomedical and nanotechnological applications. The continuous developments in protein science, increasing computing power, new algorithms, and characterization techniques provide sophisticated toolkits for solubility design beyond guess work. In this review, we summarize recent advances in the protein design field with respect to water solubility and structural stability. After introducing fundamental design rules, we discuss the transmembrane protein solubilization and transmembrane protein design. Traditional strategies to enhance protein solubility and structural stability are introduced. The designs of stable protein complexes and high-order assemblies are covered. Computational methodologies behind these endeavors, including structure prediction programs, machine learning algorithms, and specialty software dedicated to the evaluation of protein solubility and aggregation, are discussed. The findings and opportunities for Cryo-EM are presented. This review provides an overview of significant progress and prospects in accurate protein design for solubility and stability.
Topics: Amino Acids; Protein Conformation; Proteins; Software; Solubility; Water
PubMed: 35921495
DOI: 10.1021/acs.chemrev.1c00757 -
Molecules (Basel, Switzerland) Nov 2022Cantharidin (CTD) is the main active ingredient isolated from Mylabris, and norcantharidin (NCTD) is a demethylated derivative of CTD, which has similar antitumor... (Review)
Review
Cantharidin (CTD) is the main active ingredient isolated from Mylabris, and norcantharidin (NCTD) is a demethylated derivative of CTD, which has similar antitumor activity to CTD and lower toxicity than CTD. However, the clinical use of NCTD is limited due to its poor solubility, low bioavailability, and toxic effects on normal cells. To overcome these shortcomings, researchers have explored a number of strategies, such as chemical structural modifications, microsphere dispersion systems, and nanodrug delivery systems. This review summarizes the structure-activity relationship of NCTD and novel strategies to improve the solubility and bioavailability of NCTD as well as reduce the toxicity. This review can provide evidence for further research of NCTD.
Topics: Solubility; Biological Availability; Bridged Bicyclo Compounds, Heterocyclic; Cantharidin
PubMed: 36431851
DOI: 10.3390/molecules27227740 -
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 -
Drug Discovery Today Feb 2024Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited... (Review)
Review
Poor solubility of drugs and therapeutic candidates poses a significant challenge in drug research and development. Biopharmaceutical class II drugs exhibit limited absorption because of their weak solubility and high permeability. Co-amorphous systems (CAMs) have been studied widely as a way to improve the solubility of drugs. This review summarizes recent advancements in dual-drug CAMs, including improvements in formulation, manufacturing, and solid-state characterization, and highlights the importance of enhancing solubility and stability. It emphasizes the potential synergistic effects of two drugs in CAMs and explores formulation strategies and challenges related to maintaining the amorphous state. Case studies demonstrate the successful application of CAMs in combination therapies that offer improved therapeutic efficacy.
Topics: Polymers; Solubility; Drug Stability
PubMed: 38141778
DOI: 10.1016/j.drudis.2023.103863