Biological and intracellular fates of drug nanocrystals through different delivery routes: Recent development enabled by bioimaging and PK modeling

Lv, Yongjiu; Wu, Wei; Corpstein, Clairissa D.; Li, Tonglei; Lü, Yi

doi:10.1016/j.addr.2022.114466

Cited by 29 publications

(16 citation statements)

References 165 publications

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“…A high concentration gradient means fast diffusion of drug molecules across the intestinal membrane, which accounts for significantly higher C max (Tab. 2) (Lv et al, 2022). In addition to the conventional mechanism, namely, enhanced solubility and dissolution rate, transepithelial transport of intact nanocrystals (Zhu et al, 2022), increased adhesiveness to the gastrointestnal tract wall with a large contact area of nanocrystals, along with enhanced permeability by poloxamer (Li et al, 2011), might also be involved in the enhancement of oral absorption.…”

Section: Discussionmentioning

confidence: 99%

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability

Zhao

Ruan

X³

2023

Front. Pharmacol.

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Cryptotanshinone (CTS) is a plant product extracted from Salvia miltiorrhiza Bunge with various pharmacological significances. In addition to its activities against coronary heart disease, hyperlipidemia, stroke, hepatitis and chronic renal failure, it demonstrates antimetastatic effects. However, its clinical use is limited due to its poor aqueous solubility and oral bioavailability. Herein, CTS nanocrystals were prepared with the precipitation method followed by high-pressure homogenization using Poloxamer 407 as the stabilizer. A stable product was further obtained by lyophilization. The particle size of the CTS nanocrystals was 315.67 ± 11.02 nm, and the zeta potential was near 0 mV. The crystallinity was confirmed by DSC and PXRD. The saturation solubility was substantially increased from 0.97 ± 0.12 μg/ml to 62.29 ± 1.91 μg/ml, and the dissolution rate was also significantly accelerated. A pharmacokinetic study in rats revealed an improvement in oral bioavailability (2.87-fold) with CTS nanocrystals compared to the raw drug. In conclusion, the results of this study suggest a feasible formulation for the oral delivery of CTS.

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Section: Discussionmentioning

confidence: 99%

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability

Zhao

Ruan

X³

2023

Front. Pharmacol.

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“…104 Apart from conventional clinical or preclinical oral delivery of hydrophobic drugs, drug nanocrystals can be more broadly used via other administration routes, namely, transdermal, pulmonary, ophthalmic, buccal, and intravenous. [117][118][119][120] The top-down milling method is not possible or requires a very long process to reduce the size of drug nanocrystals below 100 nm. For example, using the media milling technique, fenofibrate nanocrystals with the stabilizers Soluplus® and HPMC were produced with sizes of 344 nm and 642 nm, respectively.…”

Section: Drug Nanocrystalsmentioning

confidence: 99%

Section: Microfluidic Synthesis and Separation Strategies For Nano-fo...mentioning

confidence: 99%

Advanced manufacturing of nanoparticle formulations of drugs and biologics using microfluidics

Shen,

Gwak,

Han

2024

Analyst

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“…Our group has successfully developed a novel technique to measure in vivo dissolution by monitoring residual drug particles in the gastrointestinal tract (GIT) of rats through fluorescence-based live imaging . The core of the technique stems from aggregation-caused quenching (ACQ) fluorophores that are physically embedded in crystal lattice to illuminate drug particles. − Once the ACQ fluorophores were released due to particle dissolution and came into contact with water, the dye molecules aggregated via π–π stacking, leading to complete quenching of fluorescence. − This “on-to-off” switching enables the identification of intact drug particles by eliminating the interference from free fluorophores. − The fluorescent intensity was linearly correlated with the concentration of the residual drug particles during dissolution. The residual percentage of fluorescence in rats was recorded with time, which was converted to in vivo dissolution by the difference from 100% (Figure ).…”

Section: Introductionmentioning

confidence: 99%

Establishment of In Vitro Dissolution Based on Similarity with In Vivo Dissolution: A Case Study on Aripiprazole

Man

Yang

et al. 2023

Mol. Pharmaceutics

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In vitro dissolution that predicts the in vivo performance of solid preparations is extremely important in formulation optimization. Fraction absorbed (F a ) has been used to screen in vitro dissolution protocols based on the idea of in vitro−in vivo correlation (IVIVC) but failed to increase the success rate due to the inaccuracy of the F a . The essence of IVIVC is the correlation between in vitro dissolution and in vivo dissolution. We tried to establish in vitro dissolution protocol via similarity with in vivo dissolution using aripiprazole (APZ) as a model drug. Hybrid APZ crystals (APZ-HCs) were prepared by physically embedding aggregation-caused quenching (ACQ) fluorophores inside the lattice to measure the in vivo dissolution. The process did not change the physicochemical properties and crystallinity of APZ. The fluorophore illuminated APZ crystals but was quenched upon dissolution of APZ-HCs in aqueous media, enabling monitoring intact APZ-HCs in real-time. The good correlation between fluorescent quenching and dissolution of APZ-HCs justified reliable quantification of intact APZ crystals. The residual percentage of fluorescence intensity in rats treated by APZ-HCs was recorded with time, which was converted to in vivo dissolution by the difference from 100%. The in vivo dissolution was validated with the F a . The in vitro dissolution profile of APZ was set up via a similarity factor larger than 50 in comparison with the in vivo dissolution. The study provides a novel idea and method to establish in vitro dissolution protocol.

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Biological and intracellular fates of drug nanocrystals through different delivery routes: Recent development enabled by bioimaging and PK modeling

Cited by 29 publications

References 165 publications

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability

Preparation and optimization of surface stabilized cryptotanshinone nanocrystals with enhanced bioavailability

Advanced manufacturing of nanoparticle formulations of drugs and biologics using microfluidics

Establishment of In Vitro Dissolution Based on Similarity with In Vivo Dissolution: A Case Study on Aripiprazole

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