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The Journal of Physical Chemistry. A Sep 2023The Stokes-Einstein relation, which relates the diffusion coefficient of a molecule to its hydrodynamic radius, is commonly used to determine molecular sizes in chemical...
The Stokes-Einstein relation, which relates the diffusion coefficient of a molecule to its hydrodynamic radius, is commonly used to determine molecular sizes in chemical analysis methods. Here, we combine the size sensitivity of such diffusion-based methods with the structure sensitivity of Raman spectroscopy by performing Raman diffusion-ordered spectroscopy (Raman-DOSY). The core of the Raman-DOSY setup is a flow cell with a Y-shaped channel containing two inlets: one for the sample solution and one for the pure solvent. The two liquids are injected at the same flow rate, giving rise to two parallel laminar flows in the channel. After the flow stops, the solute molecules diffuse from the solution-filled half of the channel into the solvent-filled half at a rate determined by their hydrodynamic radius. The arrival of the solute molecules in the solvent-filled half of the channel is recorded in a spectrally resolved manner by Raman microspectroscopy. From the time series of Raman spectra, a two-dimensional Raman-DOSY spectrum is obtained, which has the Raman frequency on one axis and the diffusion coefficient (or equivalently, hydrodynamic radius) on the other. In this way, Raman-DOSY spectrally resolves overlapping Raman peaks arising from molecules of different sizes. We demonstrate Raman-DOSY on samples containing up to three compounds and derive the diffusion coefficients of small molecules, proteins, and supramolecules (micelles), illustrating the versatility of Raman-DOSY. Raman-DOSY is label-free and does not require deuterated solvents and can thus be applied to samples and matrices that might be difficult to investigate with other diffusion-based spectroscopy methods.
PubMed: 37656920
DOI: 10.1021/acs.jpca.3c03232 -
International Journal of Nanomedicine 2023Hyaluronic acid (HA) is a popular biological material for osteoarthritis (OA) treatment. Pioglitazone, a PPAR-γ agonist, has been found to inhibit OA, but its use is...
BACKGROUND
Hyaluronic acid (HA) is a popular biological material for osteoarthritis (OA) treatment. Pioglitazone, a PPAR-γ agonist, has been found to inhibit OA, but its use is limited because achieving the desired local drug concentration after administration is challenging.
PURPOSE
Herein, we constructed HA-based cartilage-targeted nanomicelles (C-HA-DOs) to deliver pioglitazone in a sustained manner and evaluated their efficacy in vitro and in vivo.
METHODS
C-HA-DOs were chemically synthesized with HA and the WYRGRL peptide and dodecylamine. The products were characterized by FT-IR, H NMR, zeta potential and TEM. The drug loading rate and cumulative, sustained drug release from Pio@C-HA-DOs were determined, and their biocompatibility and effect on oxidative stress in chondrocytes were evaluated. The uptake of C-HA-DOs by chondrocytes and their effect on OA-related genes were examined in vitro. The nanomicelle distribution in the joint cavity was observed by in vivo small animal fluorescence imaging (IVIS). The therapeutic effects of C-HA-DOs and Pio@C-HA-DOs in OA rats were analysed histologically.
RESULTS
The C-HA-DOs had a particle size of 198.4±2.431 nm, a surface charge of -8.290±0.308 mV, and a critical micelle concentration of 25.66 mg/Land were stable in solution. The cumulative drug release from the Pio@C-HA-DOs was approximately 40% at pH 7.4 over 24 hours and approximately 50% at pH 6.4 over 4 hours. Chondrocytes rapidly take up C-HA-DOs, and the uptake efficiency is higher under oxidative stress. In chondrocytes, C-HA-DOs, and Pio@C-HA-DOs inhibited HO-induced death, reduced intracellular ROS levels, and restored the mitochondrial membrane potential. The IVIS images confirmed that the micelles target cartilage. Pio@C-HA-DOs reduced the degradation of collagen II and proteoglycans by inhibiting the expression of MMP and ADAMTS, ultimately delaying OA progression in vitro and in vivo.
CONCLUSION
Herein, C-HA-DOs provided targeted drug delivery to articular cartilage and improved the role of pioglitazone in the treatment of OA.
Topics: Rats; Animals; Hyaluronic Acid; Pioglitazone; Hydrogen Peroxide; Spectroscopy, Fourier Transform Infrared; Osteoarthritis; Chondrocytes; Cartilage, Articular
PubMed: 37873552
DOI: 10.2147/IJN.S428938 -
Pharmaceutics Jul 2023Nucleic acids can modulate gene expression specifically. They are increasingly being utilized and show huge potential for the prevention or treatment of various... (Review)
Review
Nucleic acids can modulate gene expression specifically. They are increasingly being utilized and show huge potential for the prevention or treatment of various diseases. However, the clinical translation of nucleic acids faces many challenges due to their rapid clearance after administration, low stability in physiological fluids and limited cellular uptake, which is associated with an inability to reach the intracellular target site and poor efficacy. For many years, tremendous efforts have been made to design appropriate delivery systems that enable the safe and effective delivery of nucleic acids at the target site to achieve high therapeutic outcomes. Among the different delivery platforms investigated, polymeric micelles have emerged as suitable delivery vehicles due to the versatility of their structures and the possibility to tailor their composition for overcoming extracellular and intracellular barriers, thus enhancing therapeutic efficacy. Many strategies, such as the addition of stimuli-sensitive groups or specific ligands, can be used to facilitate the delivery of various nucleic acids and improve targeting and accumulation at the site of action while protecting nucleic acids from degradation and promoting their cellular uptake. Furthermore, polymeric micelles can be used to deliver both chemotherapeutic drugs and nucleic acid therapeutics simultaneously to achieve synergistic combination treatment. This review focuses on the design approaches and current developments in polymeric micelles for the delivery of nucleic acids. The different preparation methods and characteristic features of polymeric micelles are covered. The current state of the art of polymeric micelles as carriers for nucleic acids is discussed while highlighting the delivery challenges of nucleic acids and how to overcome them and how to improve the safety and efficacy of nucleic acids after local or systemic administration.
PubMed: 37631235
DOI: 10.3390/pharmaceutics15082021 -
Polymers May 2024Polymerization-induced self-assembly (PISA) is a powerful and versatile technique for producing colloidal dispersions of block copolymer particles with desired... (Review)
Review
Polymerization-induced self-assembly (PISA) is a powerful and versatile technique for producing colloidal dispersions of block copolymer particles with desired morphologies. Currently, PISA can be carried out in various media, over a wide range of temperatures, and using different mechanisms. This method enables the production of biodegradable objects and particles with various functionalities and stimuli sensitivity. Consequently, PISA offers a broad spectrum of potential commercial applications. The aim of this review is to provide an overview of the current state of rational synthesis of block copolymer particles with diverse morphologies using various PISA techniques and mechanisms. The discussion begins with an examination of the main thermodynamic, kinetic, and structural aspects of block copolymer micellization, followed by an exploration of the key principles of PISA in the formation of gradient and block copolymers. The review also delves into the main mechanisms of PISA implementation and the principles governing particle morphology. Finally, the potential future developments in PISA are considered.
PubMed: 38794601
DOI: 10.3390/polym16101408 -
Cureus Sep 2023Even though many of the approved drugs still have high systemic toxicity due to a lack of tumor selectivity and present pharmacokinetic drawbacks, like low water... (Review)
Review
Even though many of the approved drugs still have high systemic toxicity due to a lack of tumor selectivity and present pharmacokinetic drawbacks, like low water solubility, that negatively influence the drug circulation time and bioavailability, the anti-cancer study has produced commendable results in recent years. The stability tests carried out under stressful exposure to high temperatures, hydrolytic media, or light sources during their development or under moderate settings have shown the vulnerability of anti-cancer medications to various factors. Because of this, the development of degradation products is considered hospital waste in pharmaceutical formulations and the environment. Until now, various formulations have been created for attaining tissue-specific therapeutic targeting, lowering harmful side effects, and enhancing drug stability. To boost the specificity, efficiency, and durability of active molecules that are targeted in cancer therapy the invention of prodrugs is the potential approach. The latest study illustrates that the solubility, pharmacokinetics, cellular uptake, and stability of chemotherapy drugs can be improved through the incorporation of them into vesicular systems, such as polymeric micelles or cyclodextrins, or via nanocarriers containing chemotherapeutics linked to monoclonal antibodies. In this review article, we provide an overview of the most recent advances in the field of designing very stable prodrugs or nanosystems that are powerful anti-cancer medications and their actions on the body.
PubMed: 37859875
DOI: 10.7759/cureus.45474 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Jun 2023Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water... (Review)
Review
Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.
Topics: Antifungal Agents; Drug Delivery Systems; Amphotericin B; Liposomes; Nanoparticles; Drug Carriers
PubMed: 37476943
DOI: 10.3724/zdxbyxb-2023-0030 -
Journal of Dairy Science Mar 2024Novel insights into the stability of milk and milk products during storage and processing result from describing caseins near neutral pH as hydrophilic, intrinsically...
Novel insights into the stability of milk and milk products during storage and processing result from describing caseins near neutral pH as hydrophilic, intrinsically disordered, proteins. Casein solubility is strongly influenced by pH and multivalent ion binding. Solubility is high at neutral pH or above but decreases as casein net charge approaches zero, allowing a condensed casein phase or gel to form then increases at lower pH. Of particular importance for casein micelle stability near neutral pH is the proportion of free caseins in the micelle (i.e., caseins not bound directly to nanoclusters of calcium phosphate). Free caseins are more soluble and better able to act as molecular chaperones (to prevent casein and whey protein aggregation) than bound caseins. Some free caseins are highly phosphorylated and can also act as mineral chaperones to inhibit the growth of calcium phosphate phases and prevent mineralized deposits from forming on membranes or heat exchangers. Thus, casein micelle stability is reduced when free caseins bind to amyloid fibrils, destabilized whey proteins or calcium phosphate. The multivalent-binding model of the casein micelle quantitatively describes these and other factors affecting the stability of milk and milk protein products during manufacture and storage.
PubMed: 38522835
DOI: 10.3168/jds.2024-24779 -
Drug Delivery Dec 2023Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be... (Review)
Review
Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.
Topics: Humans; Drug Delivery Systems; Neoplasms; Micelles; Apoptosis; Biological Availability
PubMed: 36866455
DOI: 10.1080/10717544.2023.2183815