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1. Enhancing the Solubility of Co-Formulated Hydrophobic Drugs by Incorporating Functionalized Nano-Structured Poly Lactic-co-glycolic Acid (nfPLGA) During Co-Precipitation

   https://doi.org/10.3390/pharmaceutics17010077  

   Islam, Mohammad Saiful; Mitra, Somenath (January 2025, Pharmaceutics)

   Background/Objectives: The co-formulation of active pharmaceutical ingredients (APIs) is a growing strategy in biopharmaceutical development, particularly when it comes to improving solubility and bioavailability. This study explores a co-precipitation method to prepare co-formulated crystals of griseofulvin (GF) and dexamethasone (DXM), utilizing nanostructured, functionalized polylactic glycolic acid (nfPLGA) as a solubility enhancer. Methods: An antisolvent precipitation technique was employed to incorporate nfPLGA at a 3% concentration into the co-formulated GF and DXM, referred to as DXM-GF-nfPLGA. The dissolution performance of this formulation was compared to that of the pure drugs and the co-precipitated DXM-GF without nfPLGA. Results: Several characterization techniques, including electron microscopy (SEM), RAMAN, FTIR, TGA, and XRD, were used to analyze the nfPLGA incorporation and the co-precipitated co-formulations. The inclusion of nfPLGA significantly enhanced the dissolution and initial dissolution rate of both GF and DXM in the DXM-GF-nfPLGA formulation, achieving a maximum dissolution of 100%, which was not attained by the pure drugs or the DXM-GF formulation. The incorporation of nfPLGA also reduced the amount of time taken to reach 50% (T50) and 80% (T80) dissolution. T50 values decreased from 52 and 82 min (for pure DXM and GF) to 23 min for DXM-GF-nfPLGA, and the T80 improved to 50 min for DXM-GF-nfPLGA, significantly outpacing the pure compounds. Furthermore, incorporating nfPLGA into the crystal structures greatly accelerated the dissolution rates, with initial rates reaching 650.92 µg/min for DXM-GF-nfPLGA compared to 540.60 µg/min for DXM-GF, while pure GF and DXM showed lower rates. Conclusions: This work demonstrates that nfPLGA incorporation enhances dissolution performance by forming water channels within the API crystal via hydrogen-bonding interactions. This innovative nfPLGA incorporation method holds promise for developing hydrophobic co-formulations with faster solubility and dissolution rates. 

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2. Selective hydrogen bonding controls temperature response of layer-by-layer upper critical solution temperature micellar assemblies

   https://doi.org/10.1039/d0sm01997f  

   Aliakseyeu, Aliaksei; Albright, Victoria; Yarbrough, Danielle; Hernandez, Samantha; Zhou, Qing; Ankner, John F.; Sukhishvili, Svetlana A. (March 2021, Soft Matter)

   null (Ed.)

   This work establishes a correlation between the selectivity of hydrogen-bonding interactions and the functionality of micelle-containing layer-by-layer (LbL) assemblies. Specifically, we explore LbL films formed by assembly of poly(methacrylic acid) (PMAA) and upper critical solution temperature block copolymer micelles (UCSTMs) composed of poly(acrylamide- co -acrylonitrile) P(AAm- co -AN) cores and polyvinylpyrrolidone (PVP) coronae. UCSTMs had a hydrated diameter of ∼380 nm with a transition temperature between 45 and 50 °C, regardless of solution pH. Importantly, micelles were able to hydrogen-bond with PMAA, with the critical interaction pH being temperature dependent. To better understand the thermodynamic nature of these interactions, in depth studies using isothermal titration calorimetry (ITC) were conducted. ITC reveals opposite signs of enthalpies for binding of PMAA with micellar coronae vs. with the cores. Moreover, ITC indicates that pH directs the interactions of PMAA with micelles, selectively enabling binding with the micellar corona at pH 4 or with both the corona and the core at pH 3. We then explore UCSTM/PMAA LbL assemblies and show that the two distinct modes of PMAA interaction with the micelles ( i.e. whether or not PMAA binds with the core) had significant effects on the film composition, structure, and functionality. Consistent with PMAA hydrogen bonding with the P(AAm- co -AN) micellar cores, a significantly higher fraction of PMAA was found within the films assembled at pH 3 compared to pH 4 by both spectroscopic ellipsometry and neutron reflectometry. Selective interaction of PMAA with PVP coronae of the assembled micelles, achieved by the emergence of partial ionization of PMAA at pH 4 was critical for preserving film functionality demonstrated as temperature-controlled swelling and release of a model small molecule, pyrene. The work done here can be applied to a multitude of assembled polymer systems in order to predict suppression/retention of their stimuli-responsive behavior. 

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3. Hydrogen‐bonded polymer multilayer coatings via dynamic layer‐by‐layer assembly

   https://doi.org/10.1002/pol.20220473  

   Dolmat, Maksim; Kozlovskaya, Veronika; Inman, Daniel; Thomas, Claire; Kharlampieva, Eugenia (October 2022, Journal of Polymer Science)

   Abstract We developed the dynamic assembly of the hydrogen‐bonded multilayers of (poly(N‐vinylpyrrolidone/poly(methacrylic acid)) (PVPON/PMAA)) and compared their properties to the static multilayers. We found that dynamic multilayers, wherein a planar substrate is shaken during polymer adsorption, leads to a 15‐time faster deposition of the planar coatings. The thicknesses and roughness of the dynamic coatings were found to be ⁓30% larger than those of static (no shaking) multilayer films as measured by spectroscopic ellipsometry and atomic force microscopy. We examined the film growth, mechanical properties, wettability, hydration, and pH stability of the planar static and dynamic multilayers and demonstrated that these properties were insignificantly affected by the assembly mode. Both static and dynamic coatings produced microporous films when exposed to pH = 5.9, close to the film critical dissolution pH = 6. We discovered that during the release of the multilayer films into a solution to produce free‐standing films either as planar membranes or multilayer capsule shells, the molecular chain rearrangements result in the decreased roughness for both static and dynamic multilayers and lead to a decreased thickness of the dynamic multilayers. Our findings can help develop a rapid synthesis of thicker nanostructured polymer coatings for sensing and controlled delivery applications. 

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4. Design and Use of a Thermogelling Methylcellulose Nanoemulsion to Formulate Nanocrystalline Oral Dosage Forms

   https://doi.org/10.1002/adma.202008618  

   Chen, Liang‐Hsun; Doyle, Patrick_S (June 2021, Advanced Materials)

   Abstract Oral drug products have become indispensable in modern medicine because of their exceptional patient compliance. However, poor bioavailability of ubiquitous low‐water‐soluble active pharmaceutical ingredients (APIs) and lack of efficient oral drug formulations remain as significant challenges. Nanocrystalline formulations are an attractive route to increase API solubility, but typically require abrasive mechanical milling and several processing steps to create an oral dosage form. Using the dual amphiphilic and thermoresponsive properties of methylcellulose (MC), a new thermogelling nanoemulsion and a facile thermal dripping method are developed for efficient formulation of composite particles with the MC matrix embedded with precisely controlled API nanocrystals. Moreover, a fast and tunable release performance is achieved with the combination of a fast‐eroding MC matrix and fast‐dissolving API nanocrystals. Using the versatile thermal processing approach, the thermogelling nanoemulsion is easily formulated into a wide variety of dosage forms (nanoparticle suspension, drug tablet, and oral thin film) in a manner that avoids nanomilling. Overall, the proposed thermogelling nanoemulsion platform not only broadens the applications of thermoresponsive nanoemulsions but also shows great promise for more efficient formulation of oral drug products with high quality and tunable fast release. 

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5. Preserving the shape of silver nanocubes under corrosive environment by covering their edges and corners with iridium

   https://doi.org/10.1039/d0nr05969b  

   Wang, Peng; Ahn, Jaewan; Gao, Ruoqi; Qin, Dong (October 2020, Nanoscale)

   null (Ed.)

   Silver nanocubes have found use in an array of applications but their performance has been plagued by the shape instability arising from the oxidation and dissolution of Ag atoms from the edges and corners. Here we demonstrate that the shape of Ag nanocubes can be well preserved by covering their edges and corners with a corrosion-resistant metal such as Ir. In a typical process, we titrate a Na 3 IrCl 6 solution in ethylene glycol (EG) into a suspension of Ag nanocubes in an EG solution in the presence of poly(vinylpyrrolidone) (PVP) held at 110 °C. The Ir atoms derived from the reduction of Na 3 IrCl 6 by EG and Ag are deposited onto the edges and then corners for the generation of Ag–Ir core-frame nanocubes. Remarkably, our results indicate that a small amount of Ir atoms on the edges and corners is adequate to prevent the Ag nanocubes from transforming into nanospheres when heated in a PVP/EG solution up to 110 °C. We further demonstrate that these Ag–Ir nanocubes embrace plasmonic properties comparable to those of the original Ag nanocubes, making them immediately useful in a variety of applications. This strategy for stabilizing the shape of Ag nanocubes should be extendible to Ag nanocrystals with other shapes or nanocrystals comprised of other metals. 

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