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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 -
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) May 2018Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and... (Review)
Review
Cyclodextrins (CDs), a group of oligosaccharides formed by glucose units bound together in a ring, show a promising ability to form complexes with drug molecules and improve their physicochemical properties without molecular modifications. The stoichiometry of drug/CD complexes is most frequently 1:1. However, natural CDs have a tendency to self-assemble and form aggregates in aqueous media. CD aggregation can limit their solubility. Through derivative formation, it is possible to enhance their solubility and complexation capacity, but this depends on the type of substituent and degree of substitution. Formation of water-soluble drug/CD complexes can increase drug permeation through biological membranes. To maximize drug permeation the amount of added CD into pharmaceutical preparation has to be optimized. However, solubility of CDs, especially that of natural CDs, is affected by the complex formation. The presence of pharmaceutical excipients, such as water-soluble polymers, preservatives, and surfactants, can influence the solubilizing abilities of CDs, but this depends on the excipients' physicochemical properties. The competitive CD complexation of drugs and excipients has to be considered during formulation studies.
Topics: Chemical Phenomena; Chemistry, Pharmaceutical; Cyclodextrins; Solubility; Solvents
PubMed: 29751694
DOI: 10.3390/molecules23051161 -
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 -
The Journal of Physical Chemistry. B Nov 2015It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not...
It is well established that amyloid fibril solubility is protein specific, but how solubility depends on the interactions between the fibril building blocks is not clear. Here we use a simple protein model and perform Monte Carlo simulations to directly measure the solubility of amyloid fibrils as a function of the interaction between the fibril building blocks. Our simulations confirms that the fibril solubility depends on the fibril thickness and that the relationship between the interactions and the solubility can be described by a simple analytical formula. The results presented in this study reveal general rules how side-chain-side-chain interactions, backbone hydrogen bonding, and temperature affect amyloid fibril solubility, which might prove to be a powerful tool to design protein fibrils with desired solubility and aggregation properties in general.
Topics: Amyloid; Hydrogen Bonding; Solubility
PubMed: 26496385
DOI: 10.1021/acs.jpcb.5b09210 -
Biochemical Society Transactions Jun 2016Membrane proteins play crucial roles in cellular processes and are often important pharmacological drug targets. The hydrophobic properties of these proteins make full... (Review)
Review
Membrane proteins play crucial roles in cellular processes and are often important pharmacological drug targets. The hydrophobic properties of these proteins make full structural and functional characterization challenging because of the need to use detergents or other solubilizing agents when extracting them from their native lipid membranes. To aid membrane protein research, new methodologies are required to allow these proteins to be expressed and purified cheaply, easily, in high yield and to provide water soluble proteins for subsequent study. This mini review focuses on the relatively new area of water soluble membrane proteins and in particular two innovative approaches: the redesign of membrane proteins to yield water soluble variants and how adding solubilizing fusion proteins can help to overcome these challenges. This review also looks at naturally occurring membrane proteins, which are able to exist as stable, functional, water soluble assemblies with no alteration to their native sequence.
Topics: Bacteria; Bacterial Proteins; Hydrophobic and Hydrophilic Interactions; Membrane Proteins; Solubility; Water
PubMed: 27284043
DOI: 10.1042/BST20160025 -
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