Stimuli-Responsive Amphiphilic Pillar[<i>n</i>]arene Nanovesicles for Targeted Delivery of Cancer Drugs

Fahmy, Sherif Ashraf; Ramzy, Asmaa; Saleh, Basma; Azzazy, Hassan M. E.

doi:10.1021/acsomega.1c04297

Cited by 17 publications

(39 citation statements)

References 24 publications

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“…CDs are amphiphilic cyclic oligosaccharides obtained from the enzymatic hydrolysis of starch. They comprise three types, namely, α, β, and γ-CDs, consisting of six, seven, and eight glucopyranose units, respectively [19]. In this context, 2-hydroxy propyl ß cyclodextrin (HPßCD) is a promising derivative of CDs due to its safety, high water solubility, and ability to selectively form inclusion complexes with various drug molecules [20].…”

Section: Introductionmentioning

confidence: 99%

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

et al. 2022

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Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

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Section: Introductionmentioning

confidence: 99%

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

et al. 2022

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“…With their redox-responsive properties, such nanosystems have shown remarkable results in efficiently targeting tumor tissues. 3 In this respect, Barman et al (2019) developed a spherical curcumin-loaded CB [6] supramolecular nanocapsule, formed of a 2:1 host−guest complex ratio of curcumin:CB [6] with an average size range of 80−105 nm, aiming to target cancer cells rich in Neuropilin-1 and to bind to their tubulin proteins causing tubulin depolymerization and subsequent cellular death. 34 The nanocapsule was capped with Au nanoparticles and further conjugated to a peptide ligand (CGNKRTR) which has a high targeting affinity to tumor cells rich in Neuropilin-1 receptors (such as MCF7, U87, B16F10, A549, and MDA-MB231 cells).…”

Section: Cb-based Stimuli-responsive Nanovesicles Inmentioning

confidence: 99%

“…In addition, the surface of supramolecular nanosystems can be functionalized with various stimuli-responsive moieties enabling the release of their cargos upon exposure to external stimuli (pH, temperature, enzyme, light, and redox reactions). , Therefore, supramolecular nanosystems would reduce the off-target adverse effects of chemotherapeutics and improve their selective targeting, biological distribution, stability, solubility, and ultimately therapeutic efficiency. ,− Thus, such macrocyclic nanovesicular delivery systems hold great potential for cancer treatment and tumor targeting. This review presents state-of-the-art approaches for designing single or multiple stimuli-responsive CB-based nanovesicles for efficient cancer therapy.…”

Section: Supramolecular Nanovesicles For Cancer Targeted-deliverymentioning

confidence: 99%

Stimuli-Responsive Cucurbit[n]uril-Based Supramolecular Nanocarriers for Delivery of Chemotherapeutics

Alabrahim

Fahmy²,

Azzazy

2023

ACS Appl. Nano Mater.

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Chemotherapeutics commonly exhibit low bioavailability and systemic adverse effects. Supramolecular nanovesicles, such as pillar[n]arenes, calix[n]arenes, cucurbit[n]urils (CBs), and cyclodextrins, have been introduced as promising nanocarriers due to their remarkable encapsulation capacity and ability to host hydro-philic/-phobic guest molecules. Additionally, such nanovesicles can be decorated with various stimuli-responsive entities to enable drug targeting and controlled drug release. Self-assembly of amphiphilic cavitands and host−guest complexation represent the two common approaches for preparation of supramolecular nanovesicles with customizable surfaces capable of accommodating different biologically active guest molecules. CBs have been used as smart and multifunctional host macromolecules in cancer therapy. CBs are fabricated via a condensation reaction between formaldehyde and glycoluril units generating barrel-shaped supramolecules with partially enclosed cavities. The unique structure of CBs surrounding an internal hydrophobic cavity allows them to accommodate cationic and neutral guest molecules via ion-dipole and hydrophobic interactions, respectively. Additionally, CBs are stable, safe, and biocompatible, and their surfaces can be decorated with various functional targeting moieties. These advantages have promoted CBs as promising candidates for stimuli-responsive targeted delivery of chemotherapeutics. This review presents the most recent advances in the design of stimuli-responsive nanosystems based on CBs for effective cancer treatment.

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“…Supramolecular host molecules, comprising calix[n]arenes (CXs), cyclodextrins (CDs), cucurbiturils (CBs), and pillararenes, have been suggested as smart drug delivery platforms [1,22,23] and have been used as host molecules to encapsulate various chemotherapeutic drugs to improve their bioavailability, prevent their premature degradation in the bloodstream, and increase their targeted intracellular uptake into cancer cells [1][2][3]. Lately, calix[n]arenes (n = 4, 6, and 8) have been employed in drug targeting [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin

et al. 2022

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Para-sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin. Furthermore, it has been characterized using 1H NMR, mass spectrometry, elemental analysis, and UHPLC. A host-guest complex of asplatin and p-sulfocalix[4]arene (PSC4) has been developed and characterized using UV, Job’s plot analysis, HPLC, and density functional theory (DFT) calculations. The experimental and computational investigations propose that a 1:1 complex between asplatin and PSC4 is formed. The stability constant of the designed complex has been determined using Job’s plot and UHPLC and computed to be 9.1 × 104 M–1 and 8.7 × 104 M−1, which corresponds to a free energy of complexation of −6.8 kcal mol–1, while the calculated value for the inclusion free energy is −13.2 kcal mol−1. Both experimentally and theoretically estimated complexation free energy show that a stable host-guest complex can be formed in solution. The in vitro drug release study displayed the ability of the complex to release its cargo at a cancerous pH (pH of 5.5). Additionally, the asplatin/PSC4 complex is shown to be biocompatible when tested on human skin fibroblast noncancerous cells, demonstrating the highest in vitro cytotoxic activity against (MCF-7), cervical (HeLa), and lung cancer cells (A-549), with IC50 values of 0.75, 2.15, and 3.60 µg/mL, respectively. This is as compared to either cisplatin (IC50 of 5.47, 5.94 and 9.61 µg/mL, respectively) or asplatin (IC50 of 1.54, 5.05 and 3.91 µg/mL, respectively). On the other hand, the free asplatin exhibited higher cytotoxicity on cancerous cells and lower toxicity on noncancerous cells. The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent.

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Stimuli-Responsive Amphiphilic Pillar[n]arene Nanovesicles for Targeted Delivery of Cancer Drugs

Cited by 17 publications

References 24 publications

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

Stimuli-Responsive Cucurbit[n]uril-Based Supramolecular Nanocarriers for Delivery of Chemotherapeutics

Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin

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