Leveraging Framework Instability: A Journey from Energy Storage to Drug Delivery

Suresh, Kuthuru; López-Mejías, Vilmalí; Roy, Saikat; Camacho, Daniel F.; Matzger, Adam J.

doi:10.1055/s-0040-1707139

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…Reduction of crystal size to the nanoscale regime inherently increases surface area (and surface energy), accompanied by increased rates of dissolution and absorption. 178 For example, APIs within the nanoscopic channels of silica-based matrices 179 and other biodegradable materials 180,181 have demonstrated significant increases in dissolution rates when compared with bulk (micronsized) counterparts for in vitro dissolution profiles. This approach to nanosized formulations may lead to tailored pharmacokinetic release profiles, increased target delivery and enhanced therapeutic efficacy.…”

Section: Why Do We Care About Confined Polymorphs?mentioning

confidence: 99%

Crystallization and Polymorphism under Nanoconfinement

Fellah,

Dela Cruz,

Alamani

et al. 2024

Crystal Growth & Design

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Crystallization outcomes, polymorph stability rankings, and phase transformation pathways can be significantly altered when crystallization is restricted to dimensions below 1 μm. In this review, we discuss the state of the art of crystallization and polymorphism in nanoconfinement. A primer is presented regarding the prevalent theories for nucleation, their implications for nucleation in confinement, and the dependence of solubility on crystal size. The various methods for the discovery and control of polymorphs are reviewed. Polymorphism under nanoconfinement is particularly attractive because it can be advantageous with respect to stabilizing desirable amorphous or metastable crystalline forms. Various experimental methods employing nanoconfinement are discussed along with related methods of characterization. Several critical features of crystallization under nanoconfinement�differences in the properties of confined liquid phases and their bulk counterparts, the dependence of crystal thermotropic properties on size, crystal orientation, polymorphism, and crystallization kinetics�are presented.

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Section: Why Do We Care About Confined Polymorphs?mentioning

confidence: 99%

Crystallization and Polymorphism under Nanoconfinement

Fellah,

Dela Cruz,

Alamani

et al. 2024

Crystal Growth & Design

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“…Drug-delivery systems (DDSs) can be used to reduce the side effects, provide controlled release, and selectively target cancer-related diseases. − Metal–organic frameworks (MOFs) have become promising candidates as DDSs due to their well-defined structures, tunable pore size, high surface area, high loading/release of guest compounds, amphiphilic internal microenvironment, and pH-dependent degradation under simulated physiological conditions. − For example, the organic ligand 1,1′-biphenyl-4,4′-dicarboxylic acid (BPDC) has produced various porous frameworks: UiO-67 (Zr), UiO-67-(NH 2 ) 2 (Zr), bio-MOF-1 (Zn), and BPDC-Zr. ,,− These materials have been employed as carriers for the intracellular delivery of chemotherapeutic agents such as pemetrexed, 5-fluorouracil (5-FU), and Ru-90, and other pharmaceutical compounds such as brimonidine, calcein, and α-cyano-4-hydroxycinnamic acid. ,,− Specifically, 5-FU (∼6 wt %) and pemetrexed (∼18 wt %) were simultaneously loaded into UiO-67-(NH 2 ) 2 ; this MOF showed a pH-dependent release of both drugs in simulated physiological buffers . In addition, commercial BPs were employed recently to generate ALEN-, ZOLE-, and RISE-based coordination complexes and demonstrated suitable pH-dependent degradation, bone affinity [e.g., nano -Ca@ZOLE to hydroxyapatite (HA), 36%, 1 day], and cytotoxicity [e.g., nano -Ca@ALEN, relative cell viability (%RCV) = 38 ± 1% at 7.5 μM in 72 h] against the MDA-MB-231 cell line. − However, these BP-based coordination complexes did not lead to porous materials able to encapsulate guest molecules. − Furthermore, the reaction of benzene-1,4-bis(bisphosphonic acid) (BBPA), the BP analogue of benzene-1,4-dicarboxylic acid (BDC), coordinated with Ca 2+ successfully led to BBPA-Ca form I, a 3D framework with channels (7 × 12 Å) large enough to encapsulate and release 5-FU (∼30 wt %) .…”

Section: Introductionmentioning

confidence: 99%

High-Affinity Extended Bisphosphonate-Based Coordination Polymers as Promising Candidates for Bone-Targeted Drug Delivery

Carmona-Sarabia,

Quiñones Vélez,

Mojica-Vázquez

et al. 2023

ACS Appl. Mater. Interfaces

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Extended bisphosphonate-based coordination polymers (BPCPs) were produced when 1,1′-biphenyl-4,4′-bisphosphonic acid (BPBPA), the analogue of 1,1′-biphenyl-4,4′-dicarboxylic acid (BPDC), reacted with bioactive metals (Ca2+, Zn2+, and Mg2+). BPBPA-Ca (11 Å × 12 Å), BPBPA-Zn (10 Å × 13 Å), and BPBPA-Mg (8 Å × 11 Å) possess channels that allow the encapsulation of letrozole (LET), an antineoplastic drug that combined with BPs treats breast-cancer-induced osteolytic metastases (OM). Dissolution curves obtained in phosphate-buffered saline (PBS) and fasted-state simulated gastric fluid (FaSSGF) demonstrate the pH-dependent degradation of BPCPs. Specifically, the results show that the structure of BPBPA-Ca is preserved in PBS (∼10% release of BPBPA) and collapses in FaSSGF. Moreover, the phase inversion temperature nanoemulsion method yielded nano-Ca@BPBPA (∼160 d. nm), a material with measurably higher (>1.5x) binding to hydroxyapatite than commercial BPs. Furthermore, it was found that the amounts of LET encapsulated and released (∼20 wt %) from BPBPA-Ca and nano-Ca@BPBPA are comparable to those of BPDC-based CPs [i.e., UiO-67-(NH2)2, BPDC-Zr, and bio-MOF-1], where other antineoplastic drugs have been loaded and released under similar conditions. Cell viability assays show that, at 12.5 μM, the drug-loaded nano-Ca@BPBPA exhibits higher cytotoxicity against breast cancer cells MCF-7 and MDA-MB-231 [relative cell viability (%RCV) = 20 ± 1 and 45 ± 4%] compared with LET (%RCV = 70 ± 1 and 99 ± 1%). At this concentration, no significant cytotoxicity was found for the hFOB 1.19 cells treated with drug-loaded nano-Ca@BPBPA and LET (%RCV = 100 ± 1%). Collectively, these results demonstrate the potential of nano-Ca@BPCPs as promising drug-delivery systems to treat OM or other bone-related diseases because these present measurably higher affinity, allowing bone-targeted drug delivery under acidic environments and effecting cytotoxicity on estrogen receptor-positive and triple-negative breast cancer cell lines known to induce bone metastases, without significantly affecting normal osteoblasts at the metastatic site.

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“…Supramolecular chemistry finds application in many areas of chemistry, 1 such as in drug delivery, 2 3 the design of artificial molecular motors, 4 and in catalysis. 5,6 The structures and functionalities of these compounds are mainly governed by non-covalent interactions (NCIs).…”

Section: Introductionmentioning

confidence: 99%

Efficient Computation of the Interaction Energies of Very Large Non-covalently Bound Complexes

Gorges¹,

Bädorf²,

Hansen³

et al. 2022

Synlett

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We present a new benchmark set consisting of 16 large non-covalently bound systems (LNCI16) ranging from 380 up to 1988 atoms and featuring diverse interaction motives. Gas-phase interaction energies are calculated with various composite DFT, semi-empirical quantum mechanical (SQM), and force field (FF) methods and are evaluated using accurate DFT reference values. Of the employed QM methods, PBEh-3c proves to be the most robust for large systems with a relative mean absolute deviation (relMAD) of 8.5% with respect to the reference interaction energies. r2SCAN-3c yields an even smaller relMAD, at least for the subset of complexes for which the calculation could be converged, but is less robust for systems with smaller HOMO–LUMO gaps. The inclusion of Fock-exchange is therefore important for the description of very large non-covalent interaction (NCI) complexes in the gas phase. GFN2-xTB was found to be the best performer of the SQM methods with an excellent result of only 11.1% deviation. From the assessed force fields, GFN-FF and GAFF achieve the best accuracy. Considering their low computational costs, both can be recommended for routine calculations of very large NCI complexes, with GFN-FF being clearly superior in terms of general applicability. Hence, GFN-FF may be routinely applied in supramolecular synthesis planning.1 Introduction2 The LNCI16 Benchmark Set3 Computational Details4 Generation of Reference Values5 Results and Discussion6 Conclusions

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Leveraging Framework Instability: A Journey from Energy Storage to Drug Delivery

Cited by 4 publications

References 30 publications

Crystallization and Polymorphism under Nanoconfinement

Crystallization and Polymorphism under Nanoconfinement

High-Affinity Extended Bisphosphonate-Based Coordination Polymers as Promising Candidates for Bone-Targeted Drug Delivery

Efficient Computation of the Interaction Energies of Very Large Non-covalently Bound Complexes

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