Supramolecular nanoscale drug-delivery system with ordered structure

Jin, Xin; Zhu, Lijuan; Bai, Xue; Zhu, Xinyuan; Yan, Deyue

doi:10.1093/nsr/nwz018

Cited by 68 publications

(36 citation statements)

References 108 publications

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“…Host‐guest interactions between drug molecules and cyclodextrin‐containing polymers have been extensively employed to develop various therapeutic delivery systems . According to the above finding, small hydrophobic guest molecules can induce self‐assembly of PEICDs in aqueous solution.…”

Section: Resultsmentioning

confidence: 99%

Facile Engineering of Anti‐Inflammatory Nanotherapies by Host‐Guest Self‐Assembly

Yang

et al. 2020

ChemistrySelect

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Anti‐inflammatory drugs have been broadly used for the treatment of different diseases, but many of them have low water‐solubility, thereby leading to poor bioavailability and limited clinical benefits. Herein we report host‐guest assembly of nanotherapies based on different hydrophobic anti‐inflammatory drugs, in which β‐cyclodextrin (β‐CD)‐conjugated polyethyleneimine (PEICDs) were used as host polymers. The spontaneous assembly and nanotherapy formation by PEICDs was first demonstrated using a nonsteroidal anti‐inflammatory drug indomethacin, showing high loading efficiencies and loading contents. Besides inclusion interactions, hydrogen‐bonding and electrostatic forces are responsible for effective host‐guest assembly. Moreover, this facile and robust approach can be generalized to other hydrophobic drugs. Due to the amorphous distribution of loaded drug molecules in nanotherapies, they can be rapidly and completely released, with the release rate relevant to the binding free energy between drug and β‐CD. Accordingly, this host‐guest assembly strategy is promising for developing effective anti‐inflammatory nanotherapies.

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Section: Resultsmentioning

confidence: 99%

Facile Engineering of Anti‐Inflammatory Nanotherapies by Host‐Guest Self‐Assembly

Yang

et al. 2020

ChemistrySelect

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“…Besides, small molecule assembly from supramolecular interaction could also result in 100% drug loading ratio. 27 Gefitinib and tripeptide tyroservatide could co-assemble into supramolecular drug/drug delivery system via multiple intermolecular interactions, including hydrogen bonding and π-π stacking. 20 Similarly, Zhu et al 28 reported clofarabine and raltitrexed could self-assemble into nanoparticles with 100% drug loading ratio through molecular recognition.…”

Section: Small Molecule Nanodrugs Overcoming In Vitro "Barriers"mentioning

confidence: 99%

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

Mou

Yan

et al. 2020

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Small molecule nanodrugs consisting of pure drugs, drug‐drug dimers, drug‐drug conjugates, or drug derivatives could realize drug delivery by themselves without the aid of carriers, which have received abundant attention in recent decades. Avoiding the use of additional carriers, the yielded small molecule nanodrugs hold the following advantages: (a) high drug loading capacities (some of them could even reach up to 100%); (b) precise and tunable drug loading ration; and (c) no carrier‐induced long‐term toxicity. The past decade has witnessed rapid growth and advancements in this field. In this review, we will briefly introduce both in vitro “barriers” and in vivo barriers for drug delivery, and then summarize the most recent development of small molecule nanodrugs from the point of view how to engineer small molecule nanodrugs to overcome these barriers.

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“…Bearing in mind the physicochemical characteristics of CQ (cationic, hydrophilic, aromatic and low molecular-weight drug, Fig. 1, its entrapment in drug delivery systems such as nanoformulations to provide controlled and prolonged release, represents a main challenge [21][22][23]. The above statement is based on the very low capacity of this kind of molecules to undergo interactions with excipients that surpass their a nity with water, producing low drug association and, consequently, very fast drug release upon exposing the medicines to biological media [21][22][23].…”

Section: Introductionmentioning

confidence: 99%

The Critical Role of Aromatic-Aromatic Drug-Polymer Interactions to Provide Nanomedicines Containing Chloroquine: A Simple Proposal to Provide High Encapsulation, High Stability, and Prolonged Drug Release

Villamizar‐Sarmiento¹,

Moreno‐Villoslada²,

Oyarzún-Ampuero³

2020

Preprint

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Background: Chloroquine (CQ) is a drug commonly used to treat malaria. CQ has also gained interest for the treatment of other chronic diseases such as arthritis, lupus, cancer, diabetes, atherosclerosis, and dermatomyositis, among others. Since CQ is hydrophilic and low molecular-weight, attractive interactions with polymers in aqueous medium are weaker than with water, so that low encapsulation together with uncontrolled and fast release is observed. Importantly, a long-term administration of CQ is suggested, thus the development of formulations with controlled and prolonged release is desirable. Results: Here we propose the use of aromatic interactions between the cationic CQ and the FDA approved polymer poly(sodium 4-styrenesulfonate) (PSS) for the formation and stabilization of nanoparticles (NPs). The strategy consists on the simple mixture of two aqueous solutions containing the oppositelly charged molecules. UV-vis and NMR spectroscopy evidence intimate aromatic-aromatic interactions between CQ and PSS. CQ/PSS molar ratios from 0.2 to 0.5 allow obtaining NPs with spherical shape, size in the range of 170-410 nm, zeta potential from -18 to -45 mV, and particles number in the range of 0.9 - 6.6 x 1010 NPs/mL. Selected NPs (CQ/PSS molar ratio 0.4) are stable to wide variations in ionic strength (0-200 mM), pH (2-10) and temperature (20-50 °C). In addition, CQ/polymer 0.4 was also tested but with the absence of the aromatic group in the polymer, and providing smaller (70 nm), lower-concentrated (6.1 x 109 NPs/mL), and unstable particles, confirming the key role of the aromatic group. Furthermore, CQ/PSS NPs are stable during months and can be converted to a reconstitutable powder. Importantly, the selected NPs (CQ/PSS 0.4) show full drug association efficiency (100 %), very high drug loading (49 %), very high yield (89 %), and evidencing a drug entrapment/release governed by kinetic associations (≈99 %). Finally, release studies evidence a controlled and prolonged delivery. Conclusions: Considering the potential uses of CQ for chronic diseases, and the simplicity and efficiency of our proposal, it could be considered as a valuable alternative to developed nanomedicines. In addition, this strategy could be used for other drugs and polymers showing similar characteristics to CQ and PSS.

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Supramolecular nanoscale drug-delivery system with ordered structure

Cited by 68 publications

References 108 publications

Facile Engineering of Anti‐Inflammatory Nanotherapies by Host‐Guest Self‐Assembly

Facile Engineering of Anti‐Inflammatory Nanotherapies by Host‐Guest Self‐Assembly

Engineering small molecule nanodrugs to overcome barriers for cancer therapy

The Critical Role of Aromatic-Aromatic Drug-Polymer Interactions to Provide Nanomedicines Containing Chloroquine: A Simple Proposal to Provide High Encapsulation, High Stability, and Prolonged Drug Release

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