Immunostimulatory Lipid Nanoparticles from Herbal Medicine

Hasson, Tal; Takaoka, Anna; Rica, Roberto de la; Matsui, Hiroshi; Smeureanu, Gabriela; Drain, Charles Michael; Kawamura, Akira

doi:10.1111/cbdd.12250

Cited by 2 publications

(2 citation statements)

References 16 publications

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“…This indicates that other compounds in herbal extracts are involved in the formation of natural nanoparticles. In fact, some nanoparticles in herbal extracts are mainly composed of one or several plant-produced macromolecular metabolites including proteins [96][97][98], lipids [99,100], and polysaccharides [85,101].…”

Section: Isolation Identification and Composition Of Natural Nanoparticlesmentioning

confidence: 99%

Synergistic Mechanisms of Constituents in Herbal Extracts during Intestinal Absorption: Focus on Natural Occurring Nanoparticles

et al. 2020

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The systematic separation strategy has long and widely been applied in the research and development of herbal medicines. However, the pharmacological effects of many bioactive constituents are much weaker than those of the corresponding herbal extracts. Thus, there is a consensus that purer herbal extracts are sometimes less effective. Pharmacological loss of purified constituents is closely associated with their significantly reduced intestinal absorption after oral administration. In this review, pharmacokinetic synergies among constituents in herbal extracts during intestinal absorption were systematically summarized to broaden the general understanding of the pharmaceutical nature of herbal medicines. Briefly, some coexisting constituents including plant-produced primary and secondary metabolites, promote the intestinal absorption of active constituents by improving solubility, inhibiting first-pass elimination mediated by drug-metabolizing enzymes or drug transporters, increasing the membrane permeability of enterocytes, and reversibly opening the paracellular tight junction between enterocytes. Moreover, some coexisting constituents change the forms of bioactive constituents via mechanisms including the formation of natural nanoparticles. This review will focus on explaining this new synergistic mechanism. Thus, herbal extracts can be considered mixtures of bioactive compounds and pharmacokinetic synergists. This review may provide ideas and strategies for further research and development of herbal medicines.

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Section: Isolation Identification and Composition Of Natural Nanoparticlesmentioning

confidence: 99%

Synergistic Mechanisms of Constituents in Herbal Extracts during Intestinal Absorption: Focus on Natural Occurring Nanoparticles

et al. 2020

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“…14 Nnps are usually composed of proteins, polysaccharides, and lipids. [15][16][17][18][19] Importantly, Nnps can adsorb active constituents, 17,[20][21][22] carry them for absorption, 20,23,24 and distribute them to target tissues. 17 These results suggest that Nnps may affect the pharmaceutical and pharmacokinetic properties of the active constituents in herbal extracts.…”

Section: Introductionmentioning

confidence: 99%

Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics

Zhao¹,

Zhao²,

Lu³

et al. 2021

IJN

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Purpose This study aimed to evaluate the pharmaceutical and pharmacokinetic effects of the natural nanoparticles (Nnps) isolated from Coptidis Rhizoma extract on berberine hydrochloride (BBR) and systematically explore the related mechanisms. Methods Firstly, Nnps were isolated from Coptidis Rhizoma extract and then an Nnps-BBR complex was prepared. After qualitative and quantitative analysis in terms of size, Zeta potential, morphology, and composition of the Nnps and the Nnps-BBR complex, the effects of the Nnps on the crystallization of BBR were characterized. The effects of the Nnps on the solubility and dissolution of BBR were then evaluated. In addition, the effects of the Nnps on BBR in terms of cellular uptake, transmembrane transport, metabolic stability, and pharmacokinetics in mice were studied. Results The Nnps had an average size of 166.6 ± 1.3 nm and Zeta potential of −12.5 ± 0.2 mV. The Nnps were formed by denaturation of co-existing plant proteins with molecular weight < 30 kDa. The Nnps adsorbed or dispersed BBR, thereby promoting BBR transformation from crystal to amorphous form and improving its solubility and dissolution. The Nnps carried and promoted BBR uptake by human colonic adenocarcinoma (Caco-2) cells via caveolae-mediated endocytosis, reducing P-gp-mediated efflux of BBR in mice gut sacs and Madin-Darby canine kidney cells stably expressing the transporter P-gp (MDCK-MDR1) cells. Moreover, the Nnps improved BBR metabolic stability in mouse intestinal S9, promoting BBR intestinal absorption in mice, as shown by increased peak BBR concentration (C max , 1182.3 vs 310.2 ng/mL) and exposure level (AUC 0–12 h , 2842.8 vs 1447.0 ng·h/mL) in mouse portal vein. In addition, the Nnps increased BBR exposure level in mouse livers (95,443.2 vs 43,586.2 ng·h/g liver). Conclusion The proteinaceous nanoparticles isolated from Coptidis Rhizoma extract can form a natural nano-drug delivery system with BBR, thereby significantly improving the pharmacokinetics of oral BBR.

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Immunostimulatory Lipid Nanoparticles from Herbal Medicine

Cited by 2 publications

References 16 publications

Synergistic Mechanisms of Constituents in Herbal Extracts during Intestinal Absorption: Focus on Natural Occurring Nanoparticles

Synergistic Mechanisms of Constituents in Herbal Extracts during Intestinal Absorption: Focus on Natural Occurring Nanoparticles

Natural Nano-Drug Delivery System in Coptidis Rhizoma Extract with Modified Berberine Hydrochloride Pharmacokinetics

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